Archive for December, 2019

Drug Target Review lists its 10 most popular news stories from 2019, summarising the drug targets that you wanted to read about.

Drug Target Review has published a wide range of news stories this year, from the identification of novel drug targets to improvements in toxicology studies and developments in screening.

As the year draws to a close, we reflect on the biggest and most popular stories from 2019. To read the full pieces, click on the title of each news story.

A genetic analysis study revealed that variants of hundreds of genes work together in contributing to the development of Tourettes syndrome, in our tenth most popular story this year.

According to the researchers, from the Massachusetts General Hospital (MGH) and collaborators, their findings confirm that the underlying basis for Tourettes syndrome is polygenic, meaning that hundreds of small DNA changes cause the condition, rather than one inactive gene.

The scientists said their next step is to expand their sample size to around 12,000 patients, made possible with a potential international collaboration.

The study was published in the American Journal of Psychiatry.

A group of researchers identified new genetic targets on which BRCA2-driven cancer cells are dependent upon, providing a potential avenue for drug development.

The study, conducted at Brigham and Womens Hospital, used CRISPR and short-hairpin RNAs (shRNAs) to test 380 genes with a known or suspected role in DNA-damage response. This allowed the team to narrow in on the most promising genes: APEX2 and FEN1, two novel targets for breast cancer.

The results were published in Molecular Cell.

Immunotherapy treatment could reduce the persistence of HIV in patients receiving triple therapy, found a group of researchers.

The researchers, from the University of Montreal Hospital Research Centre, discovered that these therapies expose the virus to the immune system. Three proteins PD-1, LAG-3 and TIGIT were uncovered by the scientists as frequently expressed on the surface of HIV-hiding cells; these proteins are also cancer targets.

According to the team, their study could lead to the development of new HIV therapies based on cancer immunotherapies.

The study was published in Nature Communications.

Researchers at the Indiana University School of Medicine developed a blood test to measure pain and improve diagnosis. The team analysed hundreds of patient samples to reveal biomarkers in their blood, which could be used as a scale to determine pain.

According to the researchers, the biomarkers act like a signature that can be matched against a prescription database. This could allow medical professionals to select the appropriate compound and reduce pain for the patient.

The study was published in Molecular Psychiatry.

A team of scientists revealed that immune cells could be key in causing endometriosis, a pelvic pain experienced by women, through an investigation into macrophages. The study was led by researchers from Warwick Medical School and the University of Warwick.

Macrophages can adapt their function according to local signals from their surroundings and so become modified by disease. This led the researchers to add modified macrophages to a cell culture, which resulted in the production of higher levels of insulin-like growth factor-1 (IGF-1).

The team conclude that macrophages therefore present a drug target for endometriosis.

The results can be found in The FASEB Journal.

Scientists from the University of Pennsylvania imaged a molecule that induces inflammation and leads to lupus, in our fifth most popular story of 2019. The researchers discovered that the molecule is comprised of two sections: SHMT2 and BRISC, a cluster of proteins. When these two sections bind to each other, they cause inflammation.

When mice models lacking BRISC were tested, they were resistant to lupus. This led the team to conclude that a molecule which blocks BRISC and SHMT2 could be a drug target for lupus.

The findings were published in Nature.

A team of researchers reported that a CRISPR-Cas9 gene therapy which specifically reduces fat tissue and obesity-related metabolic disease was successful in mice.

The scientists, from Hanyang University, argue that their technique could be used as a way to combat type 2 diabetes and other obesity-related diseases.

Targeting Fabp4, a fatty acid metabolism gene, the researchers observed a 20 percent reduction of body weight in obese mice. It also resulted in improved insulin resistance after only six weeks of treatment.

The findings were published in Genome Research.

A compound that promotes the rebuilding of the protective sheath around nerve cells has been developed by researchers at the Oregon Health & Science University (OHSU).

The team found that the S3 compound reverses the effect of hyaluronic acid (HA) in mice. HA has been found to accumulate in the brain of patients with multiple sclerosis, and accumulation of HA

has also been linked to maturity failure of cells called oligodendrocytes, which generate myelin, the protective layer of axons.

The team therefore believe that the S3 compound could provide a therapeutic strategy for treating nervous system disorders.

The study can be found in Glia.

A group of researchers formed a complex view of the functional dysbiosis in the gut microbiome during inflammatory bowel disease (IBD), to reveal new targets for treatments.

The scientists, from theBroad InstituteofMITandHarvard University, observed microbial changes and human gene regulatory shifts from stool and blood samples of patients.

This multi-omic study enabled the team to discover that during periods of disease activity, IBD patients had higher levels of polyunsaturated fatty acids in both the blood and stool. They also identified other varying levels of nutrients and vitamins, presenting several potential drug targets.

The findings were published in Nature.

In our most popular news piece this year, researchers found that the small molecule PJ34 reduces the number of human pancreatic cancer cells in transplanted tumours by 90 percent.

The team, from Tel Aviv University, built on previous research to treat xenografts with their small molecule. It is permeable in the cell membrane, but affects human cancer cells exclusively, making it an attractive compound for development.

The scientists found that PJ34 causes a rapid cell death and in one mouse, the tumour completely disappeared. They concluded that the molecule could be a potent therapeutic against pancreatic cancer.

The results were published in Oncotarget.

Related organisationsBrigham and Women's Hospital, Hanyang University, Harvard University, Indiana University School of Medicine, Massachusetts General Hospital (MGH), MIT, Oregon Health & Science University (OHSU), Pennsylvania University, Tel Aviv University, University of Montreal Hospital Research Centre, Warwick Medical School, Warwick University

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DTR's news round-up 2019: the stories that defined the year - Drug Target Review

UMass Medical School and GE Healthcare Life Sciences have announced the companies plan to establish a new large-scale viral vector manufacturing facility that will be housed on the Worcester campus of the medical school.

The facility will be able to provide large quantities of high-quality recombinant adeno-associated virus vectors for preclinical research, according to a news release from the medical school.

The potential of gene therapy to treat human disease has finally become a reality, said Terence R. Flotte, the Celia and Isaac Haidak Professor of Medical Education, executive deputy chancellor, provost and dean of the School of Medicine and professor of pediatrics. However, the ability to move the field forward to treat additional serious diseases remains limited by the efficiency and flexibility of producing gene therapy vectors suitable for testing in new disease models."

A lack of large-scale vector manufacturing facilities has limited preclinical research capabilities, according to the news release.

Researchers often wait 12 to 24 months to secure enough vector for their research. With this facility, researchers will have access to GE Healthcares processing equipment, helping get research to the clinic faster, the medical school said.

Accelerating research that brings novel cell and gene therapies to patients is the mission of our business, said Catarina Flyborg, the general manager of cell and gene therapy at GE Healthcare Life Sciences. By partnering with UMass Medical School to create this large scale AAV manufacturing facility, we will provide researchers with the tools and AAV needed for pre-clinical research that will advance the cell and gene therapy industry and get therapies to patients faster.

The facility will be 3,220 square feet and will be fully operational in 2020. Four to six professional staff members will manage day-to-day operations, with Sylvain Cecchini, an associate professor of microbiology and physiological systems, as the core director, the statement said.

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UMass Medical School and GE Healthcare establishing manufacturing facility in Worcester - MassLive.com

WASHINGTON, Dec. 20, 2019 (GLOBE NEWSWIRE) -- via NEWMEDIAWIRE -- The Alliance for Regenerative Medicine (ARM), the international advocacy organization for the cell and gene therapy and broader regenerative medicine sector, today released the initial slate of presenting companies at the 2020 Cell & Gene Meeting on the Mediterranean. The event will be held April 15-17, 2020 in Barcelona, Spain.

The event, modeled after ARMs highly successful Cell & Gene Meeting on the Mesa, is expected to attract more than 500 attendees, including senior executives from leading cell therapy, gene therapy, and tissue engineering companies worldwide, large pharma and biotech representatives, institutional investors, academic research institutions, patient foundations, disease philanthropies, and members of the life science media community.

The second annual Cell & Gene Meeting on the Mediterranean will feature presentations by 50+ leading public and private companies, highlighting technical and clinical achievements over the past 12 months in the areas of cell therapy, gene therapy, gene editing, tissue engineering, and broader regenerative medicine technologies.

The initial slate of 2020 presenting companies includes: Adaptimmune, AGTC, Ambys Medicines, American Gene Technologies, AskBio, Aspect Biosystems, Atara, Autolus Therapeutics, Avectas, AVROBIO, Axovant Gene Therapies, bluebird bio, Bone Therapeutics, Caribou Biosciences, Celavie Biosciences, Cellatoz Therapeutics, CEVEC, Cynata Therapeutics, Flexion Therapeutics, Fraunhofer IZI, GenSight Biologics, Healios, Iovance Biotherapeutics, Kiadis Pharma, Kytopen, LogicBio Therapeutics, MeiraGTx, Minerva Biotechnologies, MolMed, Novadip Biosciences, Orchard Therapeutics, Oxford Biomedica, PDC*line Pharma, Precision BioSciences, Promethera Biosciences, PTC Therapeutics, Recombinetics, REGENXBIO, ReNeuron, Rexgenero, Sangamo, SmartPharm Therapeutics, Standards Coordinating Body for Regenerative Medicine, Theradaptive, ThermoGenesis, Tmunity Therapeutics, Ultragenyx Pharmaceutical, VERIGRAFT, and Zelluna Immunotherapy.

Additional event details will be updated regularly on the conference website http://www.meetingonthemed.com.

Registration is complimentary for investors and credentialed members of the media. To learn more and to register, please visitwww.meetingonthemed.com. For members of the media interested in attending, please contact Kaitlyn Donaldson Dupont at kdonaldson@alliancerm.org.

For interested organizations looking to increase exposure to this fields top decision-makers via sponsorship, please contact Kelly McWhinney at kmcwhinney@alliancerm.org for additional information.

About The Alliance for Regenerative Medicine

The Alliance for Regenerative Medicine (ARM) is an international multi-stakeholder advocacy organization that promotes legislative, regulatory and reimbursement initiatives necessary to facilitate access to life-giving advances in regenerative medicine worldwide. ARM also works to increase public understanding of the field and its potential to transform human healthcare, providing business development and investor outreach services to support the growth of its member companies and research organizations. Prior to the formation of ARM in 2009, there was no advocacy organization operating in Washington, D.C. to specifically represent the interests of the companies, research institutions, investors and patient groups that comprise the entire regenerative medicine community. Today, ARM has more than 350 members and is the leading global advocacy organization in this field. To learn more about ARM or to become a member, visithttp://www.alliancerm.org.

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The Alliance for Regenerative Medicine Releases Initial Slate of Presenting Companies at the 2020 Cell & Gene Meeting on the Mediterranean -...

In a recent study published by Prophecy Market Insights, titled, Global Personalized Gene Therapy Treatment Market Research Report, analysts offers an in-depth analysis of global Personalized Gene Therapy Treatment market. The study analyses the various aspect of the market by studying its historic and forecast data. The research report provides Porters five force model, SWOT analysis, and PESTEL analysis of the Personalized Gene Therapy Treatment market. The different areas covered in the report are Personalized Gene Therapy Treatment market size, drivers and restrains, segment analysis, geographic outlook, major manufacturers in the market, and competitive landscape.

Key Players of Personalized Gene Therapy Treatment Market:

Amgen, Inc., Chengdu Shi Endor Biological Engineering Technology Co., Ltd., SynerGene Therapeutics, Inc., Cold Genesys, Inc., Bellicum Pharmaceuticals, Inc., Takara Bio, Inc.,Ziopharm Oncology, Inc., , Sevion Therapeutics, Inc., OncoSec Medical, Inc., and Burzynski Clinic.

Download Sample Copy of This Report @ https://prophecymarketinsights.com/market_insight/Insight/request-sample/61

The research report, Personalized Gene Therapy Treatment Market presents an unbiased approach at understanding the market trends and dynamics. Analysts have studied the historical data pertaining to the market and compared it to the current market trends to paint an object picture of the markets trajectory. The report includes SWOT analysis and Porters five forces analysis to give the readers an in-depth assessment of the various factors likely to drive and restrain the overall market.

Market Segmentation:

Request PDF catalogue for this report @ https://prophecymarketinsights.com/market_insight/Insight/request-pdf/61

Table of Contents

Market Overview: The report begins with this section where product overview and highlights of product and application segments of the global Personalized Gene Therapy Treatment market are provided. Highlights of the segmentation study include price, revenue, sales, sales growth rate, and market share by product.

Competition by Company: Here, the competition in the global Personalized Gene Therapy Treatment market is analyzed, taking into consideration price, revenue, sales, and market share by company, market concentration rate, competitive situations and trends, expansion, merger and acquisition, and market shares of top 5 and 10 companies.

Company Profiles and Sales Data: As the name suggests, this section gives the sales data of key players of the global Personalized Gene Therapy Treatment market as well as some useful information on their business. It talks about the gross margin, price, revenue, products and their specifications, applications, competitors, manufacturing base, and the main business of players operating in the global Personalized Gene Therapy Treatment market.

Market Status and Outlook by Region: In this section, the report discusses about gross margin, sales, revenue, production, market share, CAGR, and market size by region. Here, the global Personalized Gene Therapy Treatment market is deeply analyzed on the basis of regions and countries such as North America, Europe, China, India, Japan, and the MEA.

Application or End User: This part of the research study shows how different application segments contribute to the global Personalized Gene Therapy Treatment market.

Market Forecast: Here, the report offers complete forecast of the global Personalized Gene Therapy Treatment market by product, application, and region. It also offers global sales and revenue forecast for all years of the forecast period.

Upstream Raw Materials: The report provides analysis of key raw materials used in the global Personalized Gene Therapy Treatment market, manufacturing cost structure, and the industrial chain.

Marketing Strategy Analysis and Distributors: This section offers analysis of marketing channel development trends, indirect marketing, and direct marketing followed by a broad discussion on distributors and downstream customers in the global Personalized Gene Therapy Treatment market.

Research Findings and Conclusion: This is one of the last sections of the report where the findings of the analysts and the conclusion of the research study are provided.

Appendix: Here, we have provided a disclaimer, our data sources, data triangulation, market breakdown, research programs and design, and our research approach.

For More Info: https://prophecymarketinsights.com/market_insight/Global-Personalized-Gene-Therapy-Treatment-61

Contact Us:

Mr. Alex (Sales Manager)

Prophecy Market Insights

Phone: +1 860 531 2701

Email: [emailprotected]

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This post was originally published on Info Street Wire

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Personalized Gene Therapy Treatment Market To Boost CAGR Prospects (2020-2030) || PMI - Info Street Wire

Last we heard about Forma Therapeutics funding was in March, when they were laying off employees as longtime partner and benefactor Celgene then in the process of being bought out by Bristol-Myers Squibb severed ties. Cut off from what turned out to be a $757 million IV, they axed 61 staff members, hired a new CEO and began reorienting the company.

The shift has evidently managed to convince some investors. Forma announced today a $100 million Series D that will fuel the companys push to become a clinically focused biotech. The syndicate includes investors long known for taking companies toward an IPO, led by RA Capital and joined by Cormorant Asset Management, Wellington Management, Samsara BioCapital, among others.

In the last month, we have presented important proof of mechanism and differentiating clinical data for our programs in sickle cell disease, glioma, AML and NASH, new CEO Frank Lee said in a statement. We are energized by the commitment from this group of leading industry investors as we move into 2020, another critical year with multiple clinical data readouts and a new program entering the clinic.

The top program of note is a sickle cell drug called FT-4202. Unlike the recent sickle cell approvals from Novartis and Global Blood Therapeutics that attempt to relieve the diseases worst symptoms or complications, and unlike the experimental gene therapies that offer the tentative promise of a cure, FT-4202 modifies the course and underlying biology of the disease without affecting the genome. It activates an enzyme called pyruvate kinase-R that is supposed to help prevent sickling and help hemoglobin bind to oxygen.

Forma announced data from the first Phase I/II trial at ASH but only mentioned positive PK and safety results.

Much has changed at Forma since March. In addition to sickle cell, they also presented early data on glioma (a type of brain tumor), NASH and acute myeloid leukemia. Lee was brought in from Genentech to replace Steve Tregay, who had led the company since founding it in 2009. In September, they hired a new CFO and a new general counsel and promoted Patrick Kelly to CMO and Brian Lesser to therapeutic head.

Forma had for much of its life relied on several partnerships, most prominently a collaboration with Celgene that began in 2013 to develop drugs in oncology and eventually expanded to a handful of other fields. That partnership came to a sudden halt in the last few days of 2018 as the NJ-based giant prepared to announce a merger with Bristol-Myers Squibb. Documents Celgene filed as part of that buyout revealed they had given Forma $757 million over the life of the deal.

The sudden closure left the biotech facing key questions about its future. They cut staff, including 25 members of their discovery group, and began pivoting toward late-stage development. Their most advanced program is in AML, where a pivotal study is now enrolling patients.

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Forma Therapeutics bounces back from Celgene fallout with $100 million Series D - Endpoints News

Latest Report on the CNS Gene Therapy Market

Persistence Market Research (PMR) recently published a market study that offers critical insights related to the growth prospects of the CNS Gene Therapy Market during the forecast period 2018 2028. The report takes into account the historical and current market trends to evaluate the top factors that are likely to influence the growth of the market in the upcoming years.

As per the report, the CNS Gene Therapy Market is poised to grow at a CAGR of ~XX% during the assessment period primarily driven by a growing focus on product innovation, a surge in demand for the CNS Gene Therapy in the developed regions, and potential opportunities in the developing regions.

ThisPress Release will help you to understand the Volume, growth with Impacting Trends. Click HERE To get SAMPLE PDF (Including Full TOC, Table & Figures) athttps://www.persistencemarketresearch.co/samples/27514

What Sets Us Apart from the Rest?

The presented market study bifurcates the CNS Gene Therapy Market on the basis of geography, applications, and end-use industries.

The competitive outlook section touches upon the business prospects of some of the most established market players in the CNS Gene Therapy Market. The company profiles of each company are included in the report along with data including revenue growth, production capacity, domestic and regional presence, product portfolio, and more.

Essential findings of the report:

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key players and product offerings

In order to get a strategic overview of the market,Access Research Methodology Prepared By Experts athttps://www.persistencemarketresearch.co/methodology/27514

The report aims to address the following queries related to the CNS Gene Therapy Market:

About us:

Persistence Market Research (PMR) is a third-platform research firm. Our research model is a unique collaboration of data analytics and market research methodology to help businesses achieve optimal performance.

To support companies in overcoming complex business challenges, we follow a multi-disciplinary approach. At PMR, we unite various data streams from multi-dimensional sources. By deploying real-time data collection, big data, and customer experience analytics, we deliver business intelligence for organizations of all sizes.

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This post was originally published on Market Reports Observer

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CNS Gene Therapy Market to Witness a Pronounce Growth During 2018 2028 - Market Reports Observer

Dive Brief:

Cargill and Renmatix have agreed to jointly explore new approaches for upcycling plant materials into functional food ingredients. They will use a proprietary water-based technology from Renmatix called the Plantrose Process and Cargill's preferred feedstocks to develop alternatives for emulsifiers and hydrocolloids.

The six-month partnership will test this technology for processing unused plant materials and converting them into functional food ingredients to be used in baked goods, dairy, soups, sauces and meat products, according to Food Ingredients 1st. The process doesn't require any harsh solvents, acids or costly enzymes.

Renmatix CEO Mike Hamilton said in a release the food industry is turning more to plant-based ingredients in order to deliver taste, functionality and label-friendly appeal."Upcycling, the process of transforming unused feedstocks into new, higher-value materials, is the next step in creating a more sustainable value chain and generating exciting new product benefits," he said.

This joint development agreement could benefit both Cargill and Renmatix. The former has access to plenty of raw plant-based materials that might otherwise be wasted, while the latter has developed a patented process to break down biomass into more environmentally friendly ingredients using just water pressure and heat.

Because Renmatix's process is so different than the chemical-based ways of making such ingredients, it could appeal to consumers wanting cleaner labels and more reused materials.

Renmatix has already developed a product called Nouravant, which is made from upcycled maple fiber. It is used for emulsification and shelf life extension two sought-after qualities for CPG manufacturers in products including baked goods. The company said in a May releasethat its plant-based Nouravant isn't subject to price and supply volatility as animal-based ingredients, so it could save food makers 25% to 50% by using it instead of conventional ingredients, like using Nouravant to replace eggs in cookies.

Manufacturers may also be interested in potential savings from new ingredients developed through this joint agreement. More natural products might help avoid commonly used emulsifiers such as mono- and diglycerides and could help trim operational costs and improve product performance, Renmatix CEO Mike Hamilton told Food Ingredients 1st.

Cargill Global Texturizers and Specialties Strategic Marketing Lead Yusuf Wazirzada told Food Navigator the company had identified some raw materials it will focus on with Renmatix's water-based technology, but did not say what they are for competitive reasons.

Other ingredients companies are working on using upcycled ingredients and they're tapping into the growing market for sustainability.According to Future Marketing Insights, the food waste business is worth $46.7 billion in 2019 and could grow 5% during the next decade.

There are many startups and Big Food players getting into this trend.Planetarians has developed a protein flour from defatted sunflower seeds left over from oil extraction, AB InBev has invested in beverage startup Canvas on fiber-rich drinks using spent grains and ReGrained has used them in granola bars.

Besides a large supply of raw plant-based materials corn and wheat are two major ones Cargill also offers its significant influence and reach within the food and ingredients industry. This could mean a greater focus on reducing the problem of food waste and pushing upcycling into becoming an even bigger trend in 2020 and beyond.

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Cargill and Renmatix collaborate to develop upcycled ingredients - Food Dive

OTTAWA Call it the case of the missing icebreaker.

The fate of the Canadian Coast Guard's next heavy icebreaker has been wrapped in mystery since the federal government quietly removed the $1.3-billion project from Vancouver shipyard Seaspan's order book in May.

But plans to build the icebreaker, which was first promised by Stephen Harper's Conservative government more than a decade ago, have not been cancelled, says Coast Guard Commissioner Mario Pelletier.

Rather, Pelletier said the icebreaker has beensent back to the drawing board as the Coast Guard looks to update the original design to account for changes in technology and the government's requirements.

"It's still in the plan," Pelletiertold TheCanadian Press this week. "Actually, we're updating our design. It was a really good design.... Because it's been a number of years, we're just updating the design and we'll see how that unfolds and we're going to queue it somewhere."

Exactly when and where the CCGS John G. Diefenbaker, as the icebreaker is to be named, will be built and how much it will ultimately cost remains up in the air.

But Pelletier expressed confidence the icebreaker it is expected to replace, the CCGS Louis S. St-Laurent in service since 1969 will be able to operate through to the late 2020s thanks to various upgrades. That includesa recent $7.1-million life extension by Quebec's Chantier Davie shipyard.

The Diefenbaker was originally supposed to replace the St-Laurent in 2017.

"Before we decided to invest in vessel life extension, we did an extensive survey ... and they were amazed at the amount of steel left on the ship," said Pelletier, who previously served on the Louis S. St-Laurent when it was still running on steam power.

"So yes, the ship is old. (But it has)a lot of steel left so that makes it safe and the propulsion-control system and everything else have been upgraded. They were upgraded in the '90s, were upgraded four or five years ago again. So she's been extremely reliable."

Seaspan was tapped in 2011 to build Diefenbaker as part of a larger order that also included four science vessels for the Coast Guard and two navy supply ships, but it was removed from the Vancouver shipyard's order book and replaced with 16 smaller multipurpose vessels in May.

Davie has been jumping at the chance to have the Diefenbaker built at its shipyard outside Quebec City.

The federal government announced Thursday that Davie was the only shipyard to qualify for addition into Canada's multibillion-dollar shipbuilding strategy, through which Ottawa is already building new naval warships, Arctic patrol vessels and Coast Guard science ships.

While that sets the company up to win potentially billions of dollars of federal work building six medium icebreakers for the Coast Guard, it has been lobbying hard for the heavier Diefenbaker as well.

The government has said Ontario-based Heddle Shipyards, which had raised concerns from the start that the selection process was rigged in Davie's favour, did not qualify for inclusion in thestrategy. The company has said it is looking at its options.

Pelletier said no decision has been made on where the Diefenbaker will be built, adding: "The way things are starting up, we are going to start the(multipurpose vessels)and the (six) icebreakers before. When we look at all options for the polar, we'll see where it can go."

The Coast Guard commissioner applauded the government's addition of a third shipyard focused exclusively on building icebreakers as "good news" for his service given the age of its current fleet, with many ships having already exceeded their expected lifespans.

That has resulted in more unplanned breakdowns, leading to ferry-service disruptions, difficulties resupplying northern and coastal communities and complaints from industry about negative impacts on maritime trade.

"The industry both down south and up north are putting a lot of pressure for us to renew our program icebreakers," Pelletier said, referring to the main icebreaker fleet.

The Coast Guard did obtain three second-hand icebreakers for more than $800 million from Davie. The company isstill in the process of converting two of them for the Coast Guard's use to help fill the gap, but those are considered a temporary measure.

This report by The Canadian Press was first published Dec. 20, 2019.

Lee Berthiaume, The Canadian Press

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Back to the drawing board for missing heavy icebreaker: Coast Guard - Airdrie Today

As we enter a new year and the beginning of a new decade, theres no better time to make sure your digestive health aisle is well-stocked: Products that heal and nourish the gut are likely the helping hand your customers will need to achieve all their health resolutions in 2020. The composition of the gut microbiome influences every aspect of our physiology and regulatory processes, which affects not only digestive health but also systemic health and ones risk for developing diseases, asserts Samantha Ford, Business Development Director, AIDP Inc.

Indeed, over the past decade, study after study has uncovered new ways that the trillions of bacteria in the gut can influence everything from nutrition absorption to hormone balance to protection against pathogens like the flu virus. People typically consider probiotics for digestive health. However, based on scientific research it is becoming increasingly clear that they have other health benefits as well, notes Andrew G. Swick, M.S., Ph.D., Chief Scientific Officer, Life Extension. A healthy gut microbiome promotes healthy immunity, metabolism, mood, heart, liver and other organ systems.

All told, this growing awareness of the microbiome has the digestive health market booming, and it stands to soar even higher in the coming decade: A report by Grand View Research Inc. projects global sales of digestive health products will reach $57.5 billion by 2025a big jump from the $31.2 billion of 2017 (1). Significant growth is anticipated in the digestive health category, affirms Hank Cheatham, Vice President, Daiwa Health Development. With the awareness of the connection between gut health, overall health and cognitive function as well as athletic performance, growth seems to be a sure thing. In addition, researchers have only just begun to identify methodology to define a healthy microbiome; as this investigation evolves, growth in the market will occur, not only in personalized medicine, but overall.

That said, its not just probiotics and other microbiome-nourishing supplements fueling the market. Theres also a big opportunity to gain loyal customers who are dealing with specific digestive complaints like IBS, GERD and leaky gut and want to avoid the side effects and costs associated with traditional OTC and prescription treatments. According to the Natural Marketing Institutes (NMI)/Nielsens recently published report Opportunities in Digestive Health, 37% of consumers consider themselves to be managing some type of digestive health issue, Cheatham notes. People look to digestive remedies to help with the side effects of unhealthy diets and stressful lifestyles.

To help you navigate this increasingly flooded market so you can point your customers in the right direction to optimize their health, we tapped leading industry insiders for the low-down on the most promising new trends and technological advances in probiotics and microbiome support, as well as the research-backed natural options for the most common digestive concerns.

A study published in the journal Frontiers in Pharmacology posited that if everyone in the U.S. took probiotics, health care payers would save an estimated $373 million in medical bills and sick days would be reduced by 54.5 million, saving the economy approximately $1.4 billion per year in medical costs and lost productivity (2). And thats just savings associated with probiotics immune-boosting ability to fend off respiratory tract infections that cause cold and flu-like symptoms in healthy individuals.

With recent scientific advances, probiotics for obesity, dental health, diabetes and even heart disease could become a reality over the next decade. A wide variety of probiotic strains are being investigated for viability in specific health areas, such as oral health, mood/cognitive support, cholesterol management and more, notes Sam Michini, Vice President of Marketing & Strategy, Deerland Probiotics & Enzymes. Condition-specific action and support is the future of probiotics.

Dr. Swick agrees. With advancing technology, scientists have been able to select specific strains of organisms to accomplish precise tasks. Here, just a few strains shown to deliver targeted benefits that are already on the market:

Immune support. More than 70% of your immune system is in your gut, says Dr. Swick. He recommends a probiotic blend like Life Extensions Immune Support that combines B. lactis BS01, L. plantarum LP01, L. plantarum LP02, L. rhamnosus LR04, and L. rhamnosus LR05, which have been demonstrated to promote a healthy immune response.

Mood support. Experts estimate that up to 90% of the bodys serotonin is produced in the gut. Clinical and pre-clinical studies indicate that gut microbes can support mood and behavior by affecting the gut-brain axis, a complex communication network that links your gut with your brain, explains Dr. Swick, noting that innovative probiotic strains, L.helveticus Rosell-52 and B. longum Rosell-17, which are found in Life Extensions Florassist Mood Improve, are particularly helpful here: In two randomized controlled trials, study participants given these strains reported significant mood, stress response and emotional balance support as compared to placebo.

Also of interest for women who are pregnant or have recently given birth: The probiotic strain Lactobacillus rhamnosus HN001 is backed by clinical data in mood and anxiety support post-partum, says Ford. AIDPs Actazin in combination with HN001 has been shown to fuel the growth by as much as 140% in-vitro.

Fitness performance: Our spore-forming probiotic strain, Bacillus subtilis DE111, has the science to show its viability in fitness and athletic achievement, notes Michini. He points to a recent study published in the Journal of Strength and Conditioning Research that showed DE111, in conjunction with adequate post-workout nutrition, produced statistically significant improvements in the reduction of body fat percentage, and a strong trend indicating improved performance of the deadlift exercise (3.) In a separate study, DE111 was also found to promote tissue recovery and reduce the likelihood of injury.Weight management.Studies have suggested that there is an association between gut bacterial diversity and body weight, notes Dr. Swick. While specific strains are still being investigated, L. rhamnosus and L. gasseri show great promise in preliminary studies.

Whether your customers are shopping for a general health probiotic or a benefit-specific one, its better to focus on getting a diverse mix of bacteria strains rather the quantity or number of live active cultures, advises Neil E. Levin, CCN, DANLA, Senior Nutrition Education Manager, NOW Foods. Diversity and variety are important for gut health. A healthy gut will have no fewer than 50 to 100 probiotic strains present and that amount is actually at the low end of whats required. He notes that NOW Foods generally provides between at least 8 to 10 strains in their probiotic formulas to help foster this diversity.

Diversity can also be achieved by combining targeted strains found in a supplement along with probiotic food sources like yogurt, kimchi, kombucha and kefir, as well as functional snacks enriched with heat-resistant microbes like Kerrys spore-forming probiotic GanedenBC30. Some experts also recommend changing up the brand or formula of your probiotic supplement every few months to introduce new strains to the microbiome.

Trisha Sugarek MacDonald, BS, MS, Sr. Director of Research & Development/National Educator, Bluebonnet Nutrition Corporation, adds that its also critical to understand the quality of the probiotic, and each strains specific applications. Genetic DNA identification is the only way to ensure that you are getting the most effective probiotic strains, she says, noting that all probiotic strains in Bluebonnets Advanced Choice SingleDaily Probiotic formulas have been genetically identified and characterized by the Pasteur Institute, the scientific non-profit foundation dedicated to the study of microorganisms. Depending on ones food sensitivities, dietary benefits, such as made with non-GMO ingredients and free of most allergens, may also be important to look for on the label.

Survivability through the GI tract is also a consideration, but Levin believes theres little need to sweat it. We all know that probiotic foods are often effective without special delivery systems, and fortunately for both consumers and manufacturers, many modern probiotics are robustly acid-tolerant. For example, acidophilus literally means acid loving, he notes. Acidophilus and other common strains such as bifidobacteria have been tested for their ability to survive stomach acid for an hour at body temperature, and are rated at over 90% survivability. That can eliminate the need for enteric coatings, which contain some controversial ingredients and add to costs.

Many of the health-promoting effects of a balanced microbiome come not from the probiotics themselves, but from the short-chain fatty acids that are produced when bacteria ferment indigestible fibers, dubbed prebiotics, as food. Fermentation of certain fibers leads to the production of short-chain fatty acids, other metabolites and some vitamins, explains Kyle Krause, Product Manager, Functional Fiber and Carbohydrates, Beneo. Science demonstrates that short-chain fatty acids, achieved through this prebiotic fermentation, can reach the brain and other organs directly through the blood, or indirectly via the stimulation of immune cells, the hormonal or nervous system and the release of messenger substances. As a result, the gut microbiota can influence digestive health, an individuals inner well-being and overall health.

These prebiotic fibers play a critical role in helping good gut bacteria to thrive and multiply. While its possible to get sufficient prebiotics from food sources (onion, garlic, artichokes, bananas, barley, oats, beans and apples are all good sources of inulin and other soluble fibers and resistant starches), Michael Bush, President and CEO, Prenexus Health and Executive Board Member of the International Probiotics Association (IPA), cautions that most people struggle to get enough through diet alone. Dietary fiber is great but only 5% of Americans consume the recommended amount of dietary fiber, so supplemental prebiotics are necessary to properly feed the good bacteria that is already found in the gut. Plus, notes Cheryl Myers, Chief of Scientific Affairs and Education at EuroPharma, Inc., Supplemental prebiotics have the benefit of being consistentwhich is exactly what probiotics need to thrive.

Fortunately, theres no shortage of ingredients on the market that are effective in small doses and can be easily snuck into functional food and beverage. For instance, inulin and oligofructose, such as BENEOs chicory root fiber-derived Orafti Inulin and Oligofructose, can be easily and undetectably added to food and drink products, and have been shown to contribute to better digestive health and inner well-being by first and foremost selectively promoting the growth of beneficial microbiota, notes Krause. Studies also show improvements in bowel regularity as well as in calcium absorption and thus bone health. BENEOs prebiotic fibers have been proven to support weight management. This all results in an improved quality of life.

Xylooligoscacharides, or XOS, found in AIDPs propeitary ingredient PreticX, also show promising health perks. PreticX selectively feeds beneficial bacteria, without feeding the bad bacteriacausing a favorable alteration in gut microbiome, notes Ford. This is a tremendous advantage over other, higher dose prebiotics, which tend to feed all the bacteria, without a meaningful impact in the gut ratio. She points to a clinical trial which found that a dose of 2 grams of PreticX daily significantly increased levels of the bacteroidete B. fragilis strain, without increasing the firmicutes strain Lactobacillus. This suggests that PreticX may foster a more beneficial Bacteroidetes/Firmicutes ratio, which has been linked to improved metabolic response and benefits to weight management.

Consumers who are sensitive to starch or fiber based prebiotics may want to consider emerging phage technology, advises Michini. Phages are minuscule bundles of DNA or RNA enrobed in a protein shell. Phages are diverse and abundant: there are 10-fold more phages than bacteria populations in the human body. The role of each type of phage is to overtake a specific bacterium. He explains that phages, like those found in Deerlands PreforPro, work as a dual action prebiotic. These compounds destabilize the cell wall of the bad bacteria, which then provides nutrients as well as space for the good bacteria to grow. Whats more, he notes, PreforPro is effective in a small dose (15 mg) and does not incur bloating or flatulence because it doesnt become fermented.

Also showing promise as a prebiotic: Antioxidants like anthocyanins from berries, notes Melanie Bush, Director of Science, Artemis International, Inc. Studies have shown that flavonoids essentially behave as prebiotics and modulate a healthy balance of good bacteria in the gut. Additionally, researchers studied how gut microbes can metabolize berry flavonoids into metabolites that have significant health benefits.

SOS for digestive distress

Chronic digestive issues, including inflammatory bowel disease, acid reflux and food intolerances, can be painful, frustrating and downright embarrassing. And often, the long-term side effects of the OTC and prescription treatments can be as troubling as the condition itself. Case in point: An alarming new study published in the BMJ found that extended use of proton pump inhibitors (PPIs), which are routinely prescribed to treat heartburn, ulcers and acid reflux, was associated with a 17% increased risk of early death (4). No wonder so many Americans are trying to get off their PPIs. A new survey from the University of Michigan Medical School revealed that 79% of patients had at least some concern about PPI side effects, even if they couldnt necessarily name any specific side effects, and 83% had attempted to get off of the meds without a doctors recommendation (5).

If customers come in looking for a natural solution to digestive problems, be sure to advise them to talk to their healthcare practitioner about transitioning off meds, notes Levin. But there is natural help to be found for GERD and IBD, and its largely compatible with OTC meds, notes Myers. Some consumers choose to take their OTC and the natural product together for a week or two, then slowly wean off the OTC drug. Once inflammation (especially 5-LOX inflammation, seen in many inflammatory bowel diseases) is under control or eliminated with natural products, the digestive relief and symptom remission is going to be much more sustainablewithout the potential side effects of OTCs.

Help for heartburn, acid reflux or GERD. Myers notes that the PPIs typically used to treat reflux and heartburn shut down acid production, which may temporarily stop the pain, but used long term, it leaves users vulnerable to other problems, including increased susceptibility to food poisoning, bone density loss, and increased rates of other infections. Stomach acidity is a natural barrier against microbes entering the body along with food or liquids since the low pH discourages the growth or most organisms, explains Levin. If the acidity level is too weak, foods wont be properly digested and that immune barrier would be compromised.

Whats more, Levin notes, its been estimated that perhaps half of those taking antacids have insufficient stomach acid production to enable digestion (and provide a proper immune barrier). The clinical pearl that clinical nutritionists learn is to consider the timing of heartburn after a meal. Delayed onset heartburn is an indication to look at the probability of the acid being too weak to actually digest the food, especially protein. When this is the case, he recommends exploring a supplement with betaine HCl to supplement the stomachs own acid production and pepsin, the stomach main digestive enzyme.

Other reflux soothers: Two of the best ingredients to fight heartburn and GERD naturally are d-limonene and sea buckthorn, says Myers. D-limonene is a clinically tested component of citrus oil that appears to coat and protect the stomach walls and mucosa from the potential damage of stomach acid (without interfering with acid production), and supports healthy peristalsisthe muscle action of the intestines that moves food through the digestive system. In one study, she notes, 19 adults with a history of mild to moderate symptoms of heartburn or GERD were asked to discontinue their OTC or prescription medications and take d-limonene instead. By the second day of taking d-limonene, 32% of the participants experienced symptom relief. After 14 days, 89% of the participants were symptom free.

Seabuckthorn works another way, Myers continues. It has a protective effect on the stomach and actually helps prevent and heal gastric ulcers. It also soothes the mucosal in the digestive tract. Similarly protective of the esophagus is deglycyrrhizinated licorice (DGL) extract, adds Levin. Licorice has been shown to support healthy concentrations of compounds that promote mucus production, which may provide an improved protective barrier between the delicate lining of the esophagus and the acidic stomach contents.

Help for inflammatory bowel disease. One of the most effective botanicals for dealing with IBS or other digestive issues is boswellia, says Myers. She notes that this botanical, found in BosMed Intestinal Bowel Support, fights 5-lipoxygenase (5-LOX) inflammation. Inflammation through the small bowel and colon may be one of the physical causes and effects of IBS and other diseases. Because boswellia stops the 5-LOX cascade, it is a valuable ally. For example, in the case of Crohns disease, individuals were treated with either boswellia or the drug mesalazine (a drug commonly used to treat Crohns, ulcerative colitis, and IBS). Boswellia performed as well as the drug, but without the dangerous side effects.

Another smart supplement: Zinc L-carnosine offers a comprehensive approach to protect your stomach lining and promote gastric health, notes Levin. Several clinical studies showed that 150mg daily of zinc L-carnosine significantly reduced factors associated with gastric discomfort within eight weeks.

Help for food sensitivities or intolerances. A broad-spectrum enzyme blend can be a great solution for those who experience digestive discomfort when they eat, as it helps facilitate better digestion of the many components of a mealfats, carbohydrates and proteins, says Michini. But if a food sensitivity is claimed by your customer to be an issue, point them to supplements containing specific enzymes. Deerland makes a trio of targeted enzyme ingredients, ProHydrolase, Dairylytic and Glutalytic, that can help customers consume hard-to-digest protein peptides (like those in meat or protein powders), dairy and gluten with fewer digestive symptoms. Glutalytic is also clinically proven to reduce levels of IgA and CRP, supporting a proper immune response, he notes.

Help for leaky gut. Leaky gut is caused when inflammatory compounds (like gluten in people with gluten intolerances) and other toxins damage the digestive tract lining, creating microscopic tears that allow endotoxins and waste to leak out of the GI tract and into the bloodstream. This is notoriously difficult to treat, but Miles Sarill, National Educator, CV Sciences, sees big potential for a raw CBD component called cannabidiolic acid (CBDA) for speedier healing. He explains that this compound, which is found in CV Sciences new raw CBD oil, is a non-psychoactive precursor to CBD that has been shown in preliminary animal studies to actually facilitate healing of the digestive health tract. CBDA cant cross the blood-brain barrier, so it goes to work within the body along with 500 other anti-inflammatory compounds in a full spectrum oil, he explains. Full spectrum raw CBD oil can be deeply supportive for both inflammation response, as well as that gut barrier and the microbiome.

When it comes to growing your digestive health sales, Dr. Swick notes, It is important to educate consumers about the importance of probiotics and how they play a beneficial role within and outside the gut. Specifically, with respect to condition specific probiotic strains and how they can complement other interventions. For example if you are promoting mood support with traditional herbs or amino acids, also consider a probiotic product that has been studied and demonstrated to support the same health concern.

Myers agrees, Having printed materials that explain the connection between gut health and overall wellness are essential, too. It gives customers something to think aboutand ideally, some other lifestyle and supplemental optionsthat can encourage them to return to the store. Also, stores can invite guest speakers and experts to talk about the connection between gut health and well-being that may resonate in more direct ways than printed material.

Dont be afraid to make use of the complexity of the digestive health in illustrations or imagesthey can draw customers in, adds Michini. The gut is the bodys main manufacturing facilityit processes all the raw materials taken in from food, beverages, supplements to pharmaceuticals. This concept works well for visual storytelling, which can be used in store on a white board or other display, as well as in social media. Get the consumer involved in a way that rewards him or her. WF

References

Grand View Research, Digestive Health Products Market Size Worth $57.54 Billion By 2025,GrandViewResearch.com. Posted 2/19. Accessed 12/3/19. https://www.grandviewresearch.com/press-release/global-digestive-health-products-market

Lenoir-Wijnkoop, et al. Probiotics Reduce Health Care Cost and Societal Impact of Flu-Like Respiratory Tract Infections in USA,Frontiers in Pharmacology. Published 8/28/19. Accessed 12/3/2019. https://www.frontiersin.org/articles/10.3389/fphar.2019.00980/full

Toohey, et al. Effects of Probiotic (Bacillus subtilis) Supplementation During Offseason Resistance Training in Female Division I Athletes,The Journal of Strength and Conditioning Research. Published 06/26/18. Accessed 12/3/2019. https://journals.lww.com/nsca-jscr/Abstract/publishahead/Effects_of_Probiotic__Bacillus_subtilis_.95273.aspx

Kristina Sauerwein, Heartburn drugs linked to fatal heart and kidney disease, stomach cancer, Washington University School of Medicine in St. Louis. Publised 5/30/19. Accessed 12/3/19. https://medicine.wustl.edu/news/popular-heartburn-drugs-linked-to-fatal-heart-disease-chronic-kidney-disease-stomach-cancer/

Jina Sawani, Many Americans Are Worried About Taking PPIs and Have Tried Stopping Them Without Doctor Approval, University of Michigan Health Lab. Published 5/22/19. Accessed 12/3/19. https://labblog.uofmhealth.org/industry-dx/many-americans-are-worried-about-taking-ppis-and-have-tried-stopping-them-without

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A Healthier New Year Starts in the Gut - WholeFoods Magazine

Key Point: Nuclear command and control is one of the most important tasks for the U.S. military.

In a military that operates Raptor stealth fighters, A-10 tank busters, B-52 bombers and Harrier jump jets, the U.S. Navys placid-looking E-6 Mercury, based on the 707 airliner, seems particularly inoffensive. But dont be deceived by appearances. Though the Mercury doesnt carry any weapons of its own, it may be in a sense the deadliest aircraft operated by the Pentagon, as its job is to command the launch of land-based and sea-based nuclear ballistic missiles.

Of course, the U.S. military has a ground-based strategic Global Operations Center in Nebraska, and land-based transmitters for communicating with the nuclear triad. However, the E-6s sinister purpose is to maintain the communication link between the national command authority (starting with the president and secretary of defense) and U.S. nuclear forces, even if ground-based command centers are destroyed by an enemy first strike. In other words, you can chop off the head of the U.S. nuclear forces, but the body will keep on coming at you, thanks to these doomsday planes.

The E-6s basic mission is known as Take Charge and Move Out (TACAMO). Prior to the development of the E-6, theTACAMOmission was undertaken by land-based transmitter and laterEC-130Gand Q Hercules aircraft, which had Very Low Frequency radios for communication with navy submarines. Interestingly, France also operated its ownTACAMOaircraft until 2001, four modifiedTransallC-160HAstarttransports, which maintainedVLFcommunications with French ballistic-missile submarines.

The first of sixteenE-6sentered service between 1989 and 1992. These were the last built in averylong line of military variants of the venerable Boeing 707 airliner, in particular the707-320BAdvanced, also used in theE-3 Sentry. Bristling with thirty-one communication antennas, theE-6Aswere originally tasked solely with communicating with submerged Navy submarines. Retrofitted with more fuel-efficientCFM-56turbojets and benefiting from expanded fuel tanks, theE-6Acould remain in the air up to fifteen hours, or seventy-two with inflight refueling.

To use its Very Low Frequency radios, an E-6 has to fly in a continuous orbit at a high altitude, with its fuselage- and tail-mounted VLF radios trailing one- and five-mile-long wire antennas at a near-vertical attitude! The VLF signals can be received byOhio-class nuclear ballistic-missile submarineshiding deep underwater, thousands of miles away. However, the VLF transmitters limited bandwidth means they can only send raw data at around thirty-five alphanumeric characters per secondmaking them alotslower than even the old 14k internet modems of the 1990s. Still, its enough to transmit Emergency Action Messages, instructing the ballistic-missile subs to execute one of a diverse menu of preplanned nuclear attacks, ranging from limited to full-scale nuclear strikes. The E-6s systems are also hardened to survive the electromagnetic pulse from nuclear weapons detonating below.

Between 1997 and 2006, the Pentagon upgraded the entire E-6A fleet to the dual-role E-6B, which expanded the Mercurys capabilities by allowing it to serve as an Airborne Nuclear Command Post with its own battle staff area for the job. In this role it serves as a backup for four huge E-4 command post aircraft based on the 747 Jumbo jet. The E-6B has ultra-high-frequency radios in its Airborne Launch Control system that enable it to remotely launch land-based ballistic missiles from their underground silos, a task formerly assigned to U.S. Air Force EC-135 Looking Glass aircraftyet another 707 variant. The E-6s crew was expanded from fourteen to twenty-two for the command post mission, usually including an onboard admiral or general. Additional UHF radios give the E-6B access to the survivable MILSTAR satellite communications network, while the cockpit is upgraded up with new avionics and instruments from the 737NG airliner. The E-6B can be distinguished in photos by its additional wing-mounted pods.

The Mercurys abundant communications gear allows it to perform nonnuclear Command, Control and Communications (C3) operations as well. For this reason, E-6s have at times been deployed to Europe and the Middle East to serve as flying C3 hubs. For example, VQ-4 was deployed in Qatar for three years from 2006 to 2009, where it relayed information such as IED blast reports and medical evacuation requests from U.S. troops in Iraq who were out of contact with their headquarters.

Two Navy Fleet Air Reconnaissance Squadrons currently operate the E-6: VQ-3 Ironmen and VQ-4 Shadows, both under the Navy Strategic Communications Wing 1. These have their home at Tinker Air Force Base in Oklahoma, but also routinely forward deploy out of Travis AFB in California and Patuxent River Naval Air Station in Maryland. At least one E-6 is kept airborne at all times. E-6s on the submarine-communication mission often fly in circles over the ocean at the lowest possible speedfor as long as ten hours at a time. Those performing the nuclear command post mission typically remain on alert near Offutt Air Force Base in Nebraska. The E-6s nuclear mission has also made its operations occasional fodder for conspiracy theorists and foreign propaganda outlets.

The E-6 platform should remain in service until 2040 thanks to a service-life extension program and continual tweaks to its systems and radios. While the Mercury has demonstrated its usefulness as an airborne communication hub for supporting troops in the field, the airborne command post will be considered a success if it never has to execute its primary mission. The heart of nuclear deterrence, after all, is convincing potential adversaries that no first strike will be adequate to prevent a devastating riposte. The E-6s are vital component in making that threat a credible one.

Sbastien Roblin holds a masters degree in conflict resolution from Georgetown University and served as a university instructor for the Peace Corps in China. He has also worked in education, editing and refugee resettlement in France and the United States. He currently writes on security and military history forWar Is Boring.

This first appeared in 2016. It is being republished due to reader interest.

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Fact: The Deadliest Aircraft Ever Carries No Weapons (It Could 'Kill' Billions) - The National Interest Online

In the world of rare diseases, patient testimonies about the extreme difficulties of receiving an accurate diagnosis for an illness are numerous. For instance, one woman, sick for most of her young life, was not properly diagnosed with idiopathic gastroparesis an ultra-rare disease that affects stomach motility and digestion until late in college after seeing numerous different specialists in multiple fields and undergoing a battery of testing.1 Another patient, now active in the rare disease advocacy community, went undiagnosed with familial partial lipodystrophy a disease that, among other things, causes selective fatty tissue loss for 37 years.2

Unfortunately, these stories are not unique. One survey indicated that it took on average 7.6 years to properly diagnose a rare disease patient in the United States.3 Another study indicated that a rare disease patient on average consulted eight different physicians before landing on an accurate diagnosis, with only 12.9 percent of respondents indicating that they had seen only one physician prior to diagnosis (23.5 percent of respondents had seen between six and 10 physicians).4 Frequently, rare disease patients exhibit similar symptoms as other, more common diseases, making diagnosis complicated and leaving patients confused and frustrated about a path forward. Further complicating the situation is that traditional treatments for more common illnesses that mimic rare disease symptoms, such as irritable bowel syndrome in the case of the aforementioned gastroparesis patient, may actually worsen a patient's condition.

As such, the misdiagnosis of rare diseases, in addition to being traumatic for patients and their families, can be extremely expensive. One study indicated that over a 10-year period, an undiagnosed rare disease patient cost over 100 percent more than the average patient. This was due in part to a significant increase in outpatient visits compared with the average patient. (The cost differential was heightened in pediatric patients.)5 Such data indicates that shortening the path to diagnosis for rare disease patients may lead not only to increase patient health but also to a significant reduction in overall long-term healthcare costs.

According to the National Institutes of Health (NIH), there may be upward of 7,000 rare diseases in the United States affecting as many as 30 million people, or nearly one-tenth of the U.S. population.6 Alarmingly, only 5 percent of identified rare diseases have an approved treatment. Despite this daunting figure, approximately 80 percent of rare diseases have genetic origins, a common factor that points to genetic (the testing of individual variants or individual/multiple genes and their effects on an individual) and genomic (the study through various methods of an individual's entire genome and its interaction with the environment) testing as logical tools for identifying and ultimately combating these illnesses.

Genetic Testing Becoming More Common

From concept to execution, the Human Genome Project at the NIH took approximately 15 years and involved the creation of the National Center for Human Genome Research (now the National Human Genome Research Institute, an official Institute at NIH), the collaboration of hundreds of national and international scientists, and an approximate, inflation-adjusted total investment of $5 billion.7,8Since that time, the cost of performing genetic and genomic testing has declined significantly, with a per-genome cost of slightly less than $1,000 in 2019 compared with per-genome costs of approximately $95 million and $30,000 in 2001 and 2010, respectively.9 This significant cost reduction, which has been associated with the development of next-generation sequencing platforms and leaps in computer hardware development, among other things, has opened the door for patients to more readily access these important resources.

Most tests fall into overall categories of DNA diagnostic testing that include single-gene tests, which can detect an abnormality in a gene associated with a particular genetic illness; whole exome sequencing, which sequences the protein-encoding regions of genes; or whole genome sequencing, which is the most rigorous in that it involves sequencing the individual's entire genome. Given the sheer number of rare diseases and the size of the human genome, it is not surprising that there are numerous genetic tests on the market today. One study indicated that there are approximately 75,000 genetic tests on the market, or 10 issued every day.10

However, insurance coverage for these technologies is minimal and inconsistent despite recent positive reception for the increased use of enhanced technologies for patient treatment through the Precision Medicine Initiative, the NIH's Cancer Moonshot and similar programs. One study indicated that coverage for multigene testing varied drastically by disease type and that tests for broad indications or a large range of genes (i.e., those tests that may be helpful in narrowing down disease possibilities in a diagnostic profile) are frequently not covered by insurers.11 It should be noted that some progress has been made on national coverage determinations for some more widely recognized testing technologies. For instance, next-generation sequencing, a revolutionary sequencing technology that sequences genetic material multiple times simultaneously against a reference genome, received a reissued national coverage determination under the Medicare program from the Centers for Medicare & Medicaid Services (CMS) in October 2019.12 However, while this decision was significant as a model for future coverage for genetic testing services, it was only a minor first step in that it was limited only to previously untested patients with ovarian or breast cancer who are Medicare eligible.13

The large and complicated landscape of genetic testing is partially responsible for the lack of insurance coverage for these technologies. For instance, there are only about 200 standardized Current Procedural Terminology (CPT) codes to identify various types of genetic tests to insurers, other physicians, hospitals and health systems, limiting the ability for payers to systematically cover these technologies. This is especially true when applying "medical necessity criteria," which requires a provider to submit accurate information showing that a treatment or test is medically necessary to treat or diagnose a specific illness in order for it to be reimbursed by a payer. Data have shown that a majority of spending in the past several years on genetic tests has gone to noninvasive prenatal tests, cancer screening tests and multiple-gene analyses.14 This is unsurprising given that some of these technologies target pre-identified, validated markers and that newer screening methods present fewer risks for patients than other, more traditional or invasive testing methods.15 For many conditions, however, showing the medical necessity of genetic testing is still a complicated and unpredictable process when a patient is in the middle or beginning of his or her diagnostic odyssey.

Thus, coverage of new genetic testing technologies continues to remain a major challenge for the medical community and a mystery for the tens of millions of U.S. patients with rare diseases. Although small-scale studies and other evidence show that the use of genetic testing as a means to more quickly and accurately diagnose patients can reduce overall health expenditures, policymakers still lack systematic data showing the effectiveness of genetic testing as a means of cutting overall health spending at a macro level.

Help on the Horizon?

Bills have been introduced as recently as the 116th Congress that would create demonstration projects to test coverage of genetic testing technologies for certain patients to help inform future expansions of genetic testing coverage. In addition, Reps. Diana DeGette (D-Colo.) and Fred Upton (R-Mich.), the original champions of the 21st Century Cures Act,16 recently issued a request for information to help inform a follow-on version of the landmark legislation dubbed "Cures 2.0."17 One of the main focuses of their inquiry is into "how Medicare coding, coverage, and payment could better support patients' access to innovative therapies." Expanded coverage to increase access to genetic testing technologies could certainly fit within this scope and would help supplement expanded access and coverage of other new and innovative healthcare technologies for rare disease patients.

Stakeholders across the rare disease landscape have also shared consistent concerns with the length of time between when a new or breakthrough medical technology is approved and when it receives coverage by insurers. Underutilized programs may help speed new technologies to the patients that need them by shortening the gap between approval and coverage. One such example is the U.S. Food and Drug Administration (FDA)-CMS parallel review program for medical devices, which was recently touted by U.S. Department of Health and Human Services (HHS) Deputy Secretary Eric Hargan at the recent FDA/CMS Summit18 and through which a next-generation sequencing test received a parallel approval and coverage determination in 2017.19 These efforts may help the scientific community and others assemble data about how greater access to these technologies positively affect patient care, provide information necessary for lawmakers to empower CMS, the FDA and others to work together on increasing coverage and access, as well as to create mechanisms to speed new technologies to patients in need.

In addition to testing expansion of coverage and access for genetic and genomic testing, further investments should be made into public-private partnerships and other information gathering networks that may centralize information from a diverse group of medical professionals to provide patients additional resources for rare disease diagnosis. For instance, the Undiagnosed Diseases Network, housed at the NIH, utilizes a dozen sites nationwide where teams of physicians assess rare disease patients and share data, including genetic testing data through a "sequencing core," to maximize the amount of national expertise available to pin down rare disease diagnoses that would be extremely difficult and expensive to receive if patients sought expertise individually.20 In addition to further investment in these resources, continued policy development and investment in the development of artificial intelligence technologies and diagnostic support software tools, which have shown promise in assisting physicians in the early detection of rare disease through symptom analysis,21 will provide additional means for patients to receive care more quickly through largely noninvasive means.

Finally, payers both public and private may lack expertise in understanding and evaluating genetic tests, especially for rare diseases. Insurers should prioritize hiring individuals to supplement their teams who have some form of advanced knowledge not only of rare diseases but also the nature of genetic testing technologies and how they are used to expedite disease diagnoses. This is especially true given the rapid development of new testing systems and the growing use of other diagnostic technologies promoted in part by provisions in the 21st Century Cures Act and other legislation.

While it typically refers to something that is uncommon, the term "rare" can also imply heightened value. Greater investment in improving the diagnostic odyssey for rare disease patients, including through greater coverage of new technologies, can only enhance the value and efficiency of the U.S. healthcare system for all patients not just the few.

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Sequence of Events: Genetic Testing Offers Significant Promise, But Coverage and Access Limited - Lexology

This years Clinical Trials on Alzheimers Disease meeting began in mid-December with a bang and ended a few days later with hallway conversations laced with worry. The topic, in both cases, was aducanumab, an experimental drug for treating people with Alzheimers disease.

The meeting got off to celebratory start as a top Biogen scientist presented results showing that the highest dose of aducanumab may benefit people with mild cognitive impairment (MCI) and elevated amounts of a protein called amyloid in the brain. That presentation represented an about-face for the company, which had pulled the plug on two trials of the drug in March.

Yet even the most enthusiastic interpreters of the drugs effects on measures of cognition and function agreed that the benefit to patients was a mild slowing, not a halt, and it was certainly not a cure for Alzheimers disease.

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But we also learned that as aducanumab clears amyloid from the brain, it can cause both microscopic hemorrhages and swelling in the brain, particularly in individuals who have a heightened genetic risk of developing Alzheimers disease dementia.

With these facts in hand, aducanumab becomes a kind of thought experiment. What if we could treat mild cognitive impairment caused by Alzheimers disease with a somewhat effective but costly and risky drug? The answers are discomforting.

For much of the 20th century, America largely ignored dementia. It was widely believed that its most common cause was senility, an extreme stage of aging. That changed in April 1976 with a 1,200-word essay titled The Prevalence and Malignancy of Alzheimer Disease: A Major Killer in the Archives of Neurology. In it, neurologist Robert Katzman argued that older adults with disabling cognitive and behavioral problems did not have senility but had Alzheimers disease, a medical problem in need of the full force of American medicine to diagnose, treat, and ideally prevent.

Nearly half a century later, America hasnt come close to solving the problem of Alzheimers disease and other causes of dementia: We dont have effective treatments and we also dont have an effective physician workforce to prescribe and administer them.

Parsing out age-related cognitive complaints from mild cognitive impairment and explaining that diagnosis is a challenging task. There arent currently enough clinicians skilled to evaluate the millions of older adults with cognitive complaints, care for those with MCI and dementia, and prescribe a costly drug that slows but does not cure Alzheimers disease and poses risks to the very same brain they are trying to treat.

Imagine that the FDA approves aducanumab, or a drug like it. Individuals with mild memory problems who dont have MCI should be sent home with reassurance or with treatments for the problems causing their memory complaints, such as anxiety, too much alcohol, or poor sleep. Those with MCI thats about 15% of older Americans would be candidates for PET scans to measure the amount of amyloid in the brain.

To evaluate the millions of Americans who see a doctor because my memory isnt as good as it used to be, overworked and underskilled clinicians are likely to take shortcuts: Never mind diagnosing mild cognitive impairment. Just order the amyloid test. If its positive, prescribe the drug. Otherwise, dont prescribe it.

That approach will be costly. A PET scan for brain amyloid costs around $4,000. Less-costly spinal fluid tests could substitute, but few clinicians are skilled at performing them. Aducanumab, as a manufactured and injected monoclonal antibody, will be expensive. The risk of small swellings and bleeds in the brain would require MRIs to assess safety, which would increase the need for clinicians skilled in interpreting the scans and adjusting treatment plans.

A drug like aducanumab presents clinicians with other novel challenges. It is one of several drugs whose risks, and possibly its benefits as well, are associated with having the ApoE4 gene a gene known to increase an individuals lifetime risk of developing Alzheimers disease dementia. The decision to start the drug may well include ApoE testing so individuals can better understand their risks and possibly responses to the drug.

Genetic testing means that clinicians will have to practice genetic counseling at visits that may need to expand from the dyad of patient and caregiver to include an extended and worried family. A prescription for aducanumab would be startling news for a patients siblings, adult children, and grandchildren: You too may have the Alzheimers gene. You too may want to have an amyloid test.

A treatment that slows Alzheimers disease, that delays the onset of dementia, promises to reduce disability and preserve autonomy. The failure to properly prescribe it could, however, increase the spectacular tallies of the time and costs of caregiving that define much of the Alzheimers crisis.

Lets assume that additional studies show that aducanumab does indeed slow the progression of Alzheimers disease with benefits that exceed its risks. Some of those who take the drug will die of other causes, such as heart disease or cancer, before dementia takes hold. But others will, in time, experience more and more disabling cognitive impairments. As they do, theyll need care.

Some will be cared for in nursing homes or facilities devoted to dementia care. Most will be cared for at home. The Alzheimers Association estimates that in 2018, 16.3 million family members and friends provided 18.5 billion hours of unpaid care to people with Alzheimers and other dementias.

This care ought to include education and training for patients and caregivers. It should also include activity programs tailored to patients abilities and disabilities. These include memory cafs, where people come together not as patients but persons, and centers whose staff members are skilled at creating days that are safe, social, and engaging, with activities such as reminiscence, music, theater, art, and exercise.

Although these ought to be the standard of care, few of them are routinely available to caregivers and patients. Doctors dont typically prescribe them, and their costs are mostly paid out of pocket. A 2013 report estimated that these out-of-pocket costs, together with the time caregivers devote to care, make up as much as half of the diseases annual $200 billion-plus cost.

A disease-slowing treatment that reduces disability ought to reduce the time spent on caregiving. But it will not allow the U.S. to ignore its fractured and disorganized system of dementia care and how this nonsystem offloads much of the costs onto patients and families. Medicare, which was created in 1965, does not pay for long-term care. We must update this antiquated law and support long-term care.

The ability to control Alzheimers disease with a drug will also demand that we engage with difficult issues regarding life and death. Disease-slowing treatments for Alzheimers will challenge our criteria for access to hospice care, as well as to physician aid in dying. Individuals with a chronic and progressive disease like Alzheimers may, in time, decide they no longer want treatment. A robust ethic of respect for persons supports their right to stop treatment. It is entirely possible that some patients, as they decline, may decide: Enough. This disease has progressed. I want to stop treatment.

After that decision or if the drug doesnt work what kind of palliative care is available when death is not in six months away but may be six years away, or longer? Medicares hospice benefit is available only to individuals with six months or fewer to live.

Physician aid in dying, which is available to residents of nine states and the District of Columbia, is also not an option. Individuals who choose this route must have a prognosis of living six months or fewer, be able to decide to end their life, and be able to take the lethal dose of medication.

We ought to be deeply concerned that the limited access to care and its cost are not perverse incentives to seek aid in dying.

We should also expect that the more we control the natural history of Alzheimers disease, the more well begin to question when were dying of it and how we should die.

Katzman foreshadowed this in closing his 1976 essay: In focusing attention on the mortality associated with Alzheimer disease, our goal is not to prolong the lives of severely demented persons, but rather to call attention to a disease whose etiology must be determined, whose course must be aborted, and ultimately a disease to be prevented.

In 2012, the National Plan to Address Alzheimers Disease premiered a strategy to achieve Katzmans vision. Goal number one was that by 2025 we will prevent and effectively treat the disease. Research on aducanumab and other drugs in the pipeline that target amyloid and other causes of neurodegeneration is one route to achieving this. Equally important is disseminating strategies that promote brain health exercise, education, smoking cessation, and the like that have been decreasing the risk of developing dementia since the 1970s.

We do this research with hope that drug interventions will help address the economic and moral costs that have transformed Alzheimers from Katzmans common disease into a crisis. At the same time, we must be mindful that these interventions will present new economic and moral costs. If we fail to address them, the crisis will endure.

Jason Karlawish, M.D., is co-director of the Penn Memory Center and a site investigator for clinical trials sponsored jointly by the National Institute on Aging and Novartis (Generations program) and the NIA and Eli Lilly (the A4 Study). You can follow him on twitter @jasonkarlawish.

Excerpt from:
Aducanumab isn't the simple solution to the Alzheimer's crisis - STAT - STAT

SPRINGFIELD As people throughout Illinois prepare to ring in the New Year, the Senate Republican Caucus is continuing to highlight new laws that will take effect on Jan. 1.

The new laws kicking off 2020 cover everything from protecting children under DCFS care to safeguarding individuals privacy and personal information.

New DCFS requirements seek to better protect children

The Department of Children and Family Services spent much of 2019 under scrutiny because of its mishandling of the abuse of a 5-year-old child, who was later beaten to death by his parents.

This tragic event, along with other mishandled issues inside the department, led the General Assembly to take a more in-depth look into the agency and pass several new requirements to better protect the children under DCFS care.

Beginning Jan. 1, DCFS will have to meet the following requirements:

House Bill 831/PA 101-0043: DCFS must notify the Department of Public Health and the Department of Healthcare and Family Services of all reports involving children alleged to have been abused or neglected while hospitalized.

House Bill 3587/PA 101-0155: DCFS must establish and maintain a toll-free number to respond to requests from the public about its post-placement and post-adoption support services.

Senate Bill 1743/PA 101-0166: DCFS must develop and conduct a standardized survey to gather feedback from children who are aging out or have transitioned out of the foster care system, and place a locked suggestion box in each group home and shelter.

House Bill 1551/PA 101-0237: DCFS must comply with several new guidelines when a child in its custody is returned to their parents or guardian.

Senate Bill 1239/ PA 101-0583: DCFS must report alleged abuse or neglect of a child by a person who is not the childs parent, a member of the childs immediate family, a person responsible for the childs welfare, an individual residing in the same home of the child or a paramour of the childs parent to the appropriate local enforcement agency.

Baby changing stations required in all public buildings

Finding a location to change your little ones diaper will be a lot easier for parents starting in 2020. House Bill 3711 requires all public buildings with restrooms open to the public to have at least one baby diaper changing station accessible to both men and women. Additionally, signs must be posted near the entrance indicating the location of the diaper changing station.

New laws protect pets

Laws protecting pets are among those that will take effect Jan. 1.

House Bill 3390 requires pet boarding facilities that do not have 24/7 staffing to be equipped with a fire sprinkler system or a fire alarm monitoring system that triggers notification to local emergency responders. This new law is in response to a fire at a West Chicago kennel that killed several animals.

Also, at the start of the New Year, cat owners will be required to have their cats vaccinated for rabies. All cats four months or older, excluding feral cats, must receive a rabies vaccination and have a subsequent vaccination within a year of the first one occurring.

New laws ensure privacy, protect personal information

Protecting individuals personal information is the intent behind several new laws taking effect Jan. 1.

House Bill 2189 prohibits direct-to-consumer commercial genetic testing companies from sharing any genetic test information or other personally identifiable information about a consumer with any health or life insurance company without written consent from the consumer.

Under Senate Bill 1624, data breaches impacting more than 500 Illinois residents as a result of a single breach must be reported in the most expedient time possible to the Attorney General.

House Bill 2408 prohibits a person from posting private compromising images of another person online. It also provides for a process for a person to obtain a take-down order to have the images removed.

The full list of January 1 new laws

Theres more to know before 2020 kicks off! To view a full list of laws taking effect January 1, visit https://bit.ly/2EfHMVQ.

Warmest wishes to you and yours for a very Merry Christmas.

If you have any additional thoughts or ideas, please visit my website at http://www.senatorstewart.com and use the form to send me an e-mail.

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From the Capitol: Heres part 2 of the new laws for Illinois - Freeport Journal-Standard

The 5,000-year-old skeleton, designated M53, with physical dysplasia. Image: S. E. Halcrow et al., 2019

The discovery of a 5,000-year-old skeleton of a young adult who had serious physical limitations suggests a form of social support existed in Neolithic China, but only to a point, as this individual may have met an untimely death.

The skeleton was found at the Guanjia site in Chinas Henan Province, and it dates back to the late Neolithic Yangshao cultural period (33002900 BCE). A recent analysis of this skeleton has revealed an array of physical and possibly cognitive health issues that would have required others to take care of this individual, according to new research published in the International Journal of Paleopathology.

Designated M53, this person had normal body proportions but was far shorter than typical, with a slender build. The researchers, a collaborative team from Queens College in New York, the University of Otago in New Zealand, and other institutions, were unable to determine the individuals sex, but the person died after reaching adulthood. M53 was buried according to normal Yangshao customs, but their hands were positioned behind their back, for reasons that arent clear. Analysis of the skeleton also revealed neck fractures, which likely contributed to M53's deathinjuries that were possibly inflicted intentionally.

Importantly, M53 had bones that were very thin and hollow, similar to severe osteoporosis, and they likely had very weak muscles, as evidenced by specific skeletal muscle markings. Taken together, this suggests M53 had physical dysplasia, leading to a kind of dwarfism, an underdeveloped body, and a feebleness. This individual wouldve been very physically limited and possibly even paralyzed. Whats more, if M53 was affected by severe hormonal problemswhich appears to be the casethey may have also experienced cognitive delays and mood disorders, according to the new research.

Ekaterina Pechenkina, a co-author of the study and an anthropologist at Queens College, said these anomalous traits may have been caused by a reduced function of the pituitary gland, a critical gland that regulates our growth and general well-being, she explained in an email to Gizmodo. Among other things, it produces the growth hormone. Indeed, her teams analysis of the skull revealed depressions in a bony structure that hosts the pituitary glanda sign that a tumor had caused the gland to stop working properly.

Pechenkina said all these skeletal manifestations suggest hypopituitarism as a diagnosis, a rare condition in which the pituitary gland cant produce sufficient hormones, leading to a host of problems, including muscle weakness. Consequently, this rare find is offering new insights into the cultural norms of the period and how individuals with noticeable physical differences or disabilities were treated.

We know that M53 was a tiny individual with very slender, fragile bones and underdeveloped muscles, who despite their limited physical abilities survived into adulthood, said Pechenkina.

Survival in this 5,000-year-old northern Chinese farming community wouldve required considerable physical strength, Pechenkina explained. Chopping wood to build fires during the cold winters wouldve been an essential skill, she said. To acquire food, people needed to turn soil, plant seeds, water crops, and so on.

I think that a slender and a fragile individual, such as M53, needed lots of support and help from their family members, said Pechenkina. It is unlikely that they were ostracized by their community, she said, as there was no evidence of abuse or signs of old fractures. And because M53 was buried in a (reasonably) typical way, they were regarded as one of their own, she said.

The exact model of care, in the words of the researchers, is unknown, but Sian Halcrow, a co-author of the study and a researcher at the University of Otago, said it very likely existed in some form.

Thats because the dysplasia likely had some associated health effects from an early age, and that would have meant M53 would have had extra care needs, said Halcrow in a press release. But they lived into adulthood so its likely they were the recipient of care from other members in their family or wider society.

That said, Pechenkina and her colleagues believe M53 likely died from the aforementioned neck fracture.

Their neck vertebrae appear to be fractured around the time of death, which makes it likely that eventually they were killed by their group members, either because they became to be seen as a burden or because their health deteriorated or, perhaps, because their caretakers became too old or died, said Pechenkina. For me, an interesting question is whether our M53 individual was recognized as different from an early childhood or only after a certain age when their short stature and fragility became apparent, she said, adding that, I suspect that up until a certain age they were likely cared for as a child.

The troublesome circumstances of M53s death notwithstanding, their survival into adulthood would have required lots of time, patience, and resourcesand also a certain degree of compassion and acceptance. Yes, the Neolithic was tough, but it was clearly far from barbaric.

No doubt, this discovery shows one way in which Neolithic culture was socially advanced, but we shouldnt be too surprised (evidence from earlier this year revealed that Neolithic European babies drank animal milk from sippy cups, as just one example). Evidence of social support goes back even further in timeas far back as the Neanderthals and other archaic humans, who cared for severely physically disabled members of their communities. Prosocial behaviors such as these, it might be argued, contributed greatly to the success of our species.

Originally posted here:
Rare Skeleton Points to Compassion, Care, and Tragedy in Prehistoric China - Gizmodo

For its promising investigational therapeutic approach to neurodegenerative diseases, including progressive multiple sclerosis (MS), BrainStorm Cell Therapeutics is theBuzz of BIO 2020 winnerin the Public Therapeutic Biotech category.

The Buzz of BIO contest identifies U.S. companies with groundbreaking, early-stage potential to improve lives. The event also is anopportunity to make investor connections that could take products to the next phase.

Ten biotechnology companies are nominated in each of the three categories of Buzz of BIO: Public Therapeutic Biotech, Private Therapeutic Biotech, and Diagnostics and Beyond. In the Public Therapeutic Biotech category that BrainStorm won, nominated companies must be actively developing a publicly traded human treatment intended for review by theU.S. Food and Drug Administration.

As a developer of autologous cellular therapies for debilitating neurodegenerative diseases, BrainStorm is testing its investigational therapy,NurOwn, in progressive MS patients, for whom treatment options are limited.

The therapy is based on patients own bone marrow-derived mesenchymal stem cells that are engineered to secrete growth factors. Such factors are thought to protect nerves from damage, promote the repair of myelin (the protective coat of neurons that is destroyed in MS), and ultimately slow or stabilize disease progression.

BrainStorms current open-label Phase 2 clinical study (NCT03799718) is enrolling up to 20 adults with either secondary progressive or primary progressive MS at three U.S. sites:theKeck School of Medicine of USC, the Stanford School of Medicine, and theCleveland Clinic. After undergoing a bone marrow aspiration to collect cells, each participant will receive three intrathecal (injected into the spinal cord) NurOwn cell transplants within 16 weeks, and will be tracked for at least another 12 weeks to assess safety and effectiveness. Contact information for the trial centers is available here.

Thanks to everyone who voted for BrainStorm during the Buzz of BIO competition,Chaim Lebovits, BrainStorm president and CEO, said in a press release.

As the winner of the contest, BrainStorm also was invited to givea presentation at theBio CEO & Investor Conference, to be held Feb. 1011 in New York City.

The entire management team at BrainStorm was very pleased with the results of this competition, and we look forward to presenting to an audience of accredited investors who may benefit from the companys story, said Lebovits. We thank the BIO[Biotechnology Innovation Organization] team for singling out BrainStorms NurOwn as a key technology with the potential to improve lives.

NurOwn cells also are being tested in a Phase 3 trial (NCT03280056) in patients with amyotrophic lateral sclerosis (ALS).

Total Posts: 1,053

Patrcia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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BrainStorm Cell Therapeutics Wins 2020 'Buzz of BIO' Award - Multiple Sclerosis News Today

SEATTLE--(BUSINESS WIRE)--According to Coherent Market Insights, the global bone graft and substitutes market is estimated to be valued at US$ 3,046.7 million in 2019, and is expected to exhibit a CAGR of 5.5% during the forecast period (2019-2027).

Key Trends and Analysis of the Global Bone Graft and Substitutes Market:

Key players in the market are focusing on receiving product approvals for bone grafts and bone graft substitutes are expected to fuel growth of the global bone graft and substitutes market over the forecast period. For instance, in December 2016, CoreBone, an Israel-based company manufacturing bone grafts from corals received approval from European Medicines Agency (EMA) for use this product in Europe, which is expected to generate a significant revenue for the region through its sales.

Request your Sample PDF copy @ https://www.coherentmarketinsights.com/insight/request-sample/1050

Moreover, adoption of inorganic growth strategies by major key players is expected to boost the market growth over the forecast period. For instance, in February 2019, Orthofix Medical acquired Options Medical, LLC, a medical device distributor based in Florida, U.S. The acquisition aims to enhance the sales force. Moreover, in 2017, LifeNet Health acquired Austria-based tissue bank- AlloTiss Gemeinntzige Gewebebank GmbH. The acquisition enabled LifeNet Health to establish training and distribution center in Vienna, Austria to support the use of allograft in Europe.

Furthermore, rising road accidents and injuries is expected to propel the market growth over the forecast period. For instance, in 2018, as per the World Health Organization (WHO) estimation, around 1.35 million people are reported to die each year due to road traffic crashes, globally.

Among regions, Asia Pacific is expected to show significant growth in the global bone graft and substitutes market, owing to increasing road accidents in the region. For instance, according to the World Health Organization report in 2013, Asia Pacific region reported around 153,000 fatalities due to road accidents or around 400 deaths each day. It also stated that road traffic death rate in South-East Asia region was 17.0 per 100,000 population, compared to the global rate of 17.4, where there was considerable variation seen within the region ranging from 3.5 in the Maldives to 36.2 in Thailand in 2015.

Key Market Takeaways:

Buy this Report (Single User License) @ https://www.coherentmarketinsights.com/insight/buy-now/1050

Market Segmentation:

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Global Bone Graft and Substitutes Market to Surpass US$ 4673.5 Million by 2027 Coherent Market Insights - Business Wire

Friday, December 20, 2019 2:40 p.m. CST

By Michael Erman

NEW YORK (Reuters) - Novartis is in discussion with patient groups over its lottery-style free drug program for its multi-million-dollar gene therapy for spinal muscular atrophy (SMA) after criticism that the process could be unfair to some babies with the deadly disease.

The company said on Friday that it will be open to refining the process in the future, but it is not making any changes at this time. The program is for patients in countries where the medicine, called Zolgensma, is not yet approved for the rare genetic disorder, which can lead to death and profound physical disabilities.

At $2.1 million per patient, Zolgensma is the world's costliest single-dose treatment.

Novartis said the program will open for submission on Jan. 2 and the first allocation of drugs would begin in February. Novartis's AveXis unit, which developed the drug, will give out 50 doses of the treatment through June for babies under 2 years old, it said on Thursday, with up to 100 total doses to be distributed through 2020.

Patient advocacy group SMA Europe had a conference call with the company on Friday, according to Kacper Rucinski, a board member of the patient and research group who was on the call.

"There are a lot of ethical questions, a lot of design questions that need to be addresses. We will be trying to address them in January," Rucinski said. He said the program has no method of prioritizing who needs the treatment most, calling it a "Russian roulette."

The company said it developed the plan with the help of bioethicists with an eye toward fairness.

"This may feel like youre blindly passing it out, but it may be the best we can do," said Alan Regenberg, who is on the faculty at Johns Hopkins' Berman Institute of Bioethics and was not among the bioethicists Novartis consulted with on the decision. "It may be impossible to separate people on the basis of prognosis out of the pool of kids under 2," he said.

According to Rucinski, the parties will continue their discussion in January "to see what can be improved in the design" of the program.

Novartis said on Thursday that because of manufacturing constraints it is focused on providing treatment to countries where the medicine is approved or pending approval. It has one licensed U.S. facility, with two plants due to come on line in 2020.

Zolgensma, hit by turmoil including data manipulation allegations and suspension of a trial over safety concerns, is the second SMA treatment, after Biogen's Spinraza.

Not all of the SMA community are opposed to Novartis' program.

Rajdeep Patgiri moved from the United Kingdom to the United States in April so his daughter could receive Zolgensma. She has responded well to the treatment, and Patgiri worries that negative attention to the program could keep patients from receiving the drug.

"The best outcome for all patients would be if everybody could get the treatment. Given all the constraints, a lottery is probably the fairest way to determine who" receives the treatment, he said.

(Reporting by Michael Erman; Additional reporting by John Miller in Zurich; Editing by Leslie Adler)

Read the rest here:
Novartis in talks with patients upset about lottery-like gene therapy giveaway - KFGO News

Gene therapy is a way of delivering healthy genes or genetic material to cells in order to treat genetic disorders. The most common way to do this is using adeno-associated viruses (AAVs). The outer part of the virus, called the capsid, is generally retained, but the viral genes are replaced with the therapeutic genes. Attempts have been made to improve the capsid or shell of the virus, but usually fail. George Church and his team at Harvard Medical School with the original researchers at the Karolinska Institute and Lund University in Sweden, have developed a technique to modify the capsid. They have also launched a company, Dyno Therapeutics, to develop the approach.

The groups research, by senior author Tomas Bjrklund, with Lund, was published in PNAS, the Proceedings of the National Academy of Sciences of the United States of America.

The technique allows the researchers to engineer the virus shell to deliver the gene package to the exact cell type in the body they intend to treat. The process leverages computer simulations and modeling with gene and sequencing technology.

Thanks to this technology, we can study millions of new virus variants in cell culture and animal models simultaneously, Bjorklund said. From this, we can subsequently create a computer simulation that constructs the most suitable virus shell for the chosen applicationin this case, the dopamine-producing nerve cells for the treatment of Parkinsons disease.

The technique also dramatically decreases the need for laboratory animals. The millions of variations on the same therapy can be studied in the same individual.

The authors wrote, A challenge with the available synthetic viruses used for the treatment of genetic disorders is that they originate from wild-type viruses. These viruses benefit form infecting as many cells as possible in the body, while therapies should most often target a particular cell type, for example, dopamine neurons in the brain.

Current approaches to finding the most advantageous viruses for gene therapy use random screening, enrichment and, the authors say, serendipity. Their technique is dubbed BRAVE (barcoded rational AAV vector evolution). In BRAVE, each virus displays a peptide derived from a protein. That peptide as a known function on the AAV shell surface and what they call a unique molecular barcode in the packaged genome.

By sequencing the RNA-expressed barcodes, they can map the binding sequences from hundreds of proteins simultaneously. They liken the technique to accelerating evolution from millions of years to just weeks.

Bjorklund said The reason we can do this is that we study each generation of the virus in parallel with all the others in the same nerve cells. Unlike evolution, where only the best suited live on to the next generation, we can also learn what makes the virus work less well through this process. This is crucial when building computer models that interpret all the information.

The study showed the potential for using machine learning for AAV design, although the research fell short of actually designing an improved AAV that could be used in clinical testing. Thats where Dyno Therapeutics comes in, working to improve and develop the technique.

Luk Vandenberghe, director of the Grousbeck Gene Therapy Center at Massachusetts Eye and Ear, told C&EN, Chemical & Engineering News, What theyve done here is truly a remarkable tour de force.

Original post:
Dyno Therapeutics Launches to Improve Viral Vectors for Gene Therapy - BioSpace

Though the research was intended as a proof of concept, the experimental gene therapy slowed tumour growth and prolonged survival in mice with gliomas, which constitute about 80% of malignant brain tumours in humans.

The technique takes advantage of exosomes, fluid-filled sacs that cells release as a way to communicate with other cells.

The research was carried out by scientists at the Ohio State University and published in the journal Nature Biomedical Engineering.

While exosomes are gaining ground as biologically friendly carriers of therapeutic materials because there are a lot of them and they dont prompt an immune response the trick with gene therapy is finding a way to fit those comparatively large genetic instructions inside their tiny bodies on a scale that will have a therapeutic effect.

This new method relies on patented technology that prompts donated human cells such as adult stem cells to spit out millions of exosomes that, after being collected and purified, function as nanocarriers containing a drug.

When they are injected into the bloodstream, they know exactly where in the body to find their target even if its in the brain.

Senior study author L. James Lee, professor emeritus of chemical and biomolecular engineering at Ohio State University, said: Think of them like Christmas gifts: the gift is inside a wrapped container that is postage paid and ready to go. This is a Mother Nature-induced therapeutic nanoparticle.

In 2017, Lee and colleagues made waves with news of a regenerative medicine discovery called tissue nanotransfection (TNT). The technique uses a nanotechnology-based chip to deliver biological cargo directly into skin, an action that converts adult cells into any cell type of interest for treatment within a patients own body.

By looking further into the mechanism behind TNTs success, scientists in Lees lab discovered that exosomes were the secret to delivering regenerative goods to tissue far below the skins surface.

The scientists placed about one million donated cells on a nano-engineered silicon wafer and used an electrical stimulus to inject synthetic DNA into the donor cells. As a result of this DNA force-feeding, as Lee described it, the cells need to eject unwanted material as part of DNA transcribed messenger RNA and repair holes that have been poked in their membranes.

The electrical stimulation had a bonus effect of a thousand-fold increase of therapeutic genes in a large number of exosomes released by the cells, a sign that the technology is scalable to produce enough nanoparticles for use in humans.

Essential to any gene therapy is knowing what genes need to be delivered to fix a medical problem. For this work, the researchers chose to test the results on glioma brain tumours by delivering a gene called PTEN, a cancer-suppressor gene. Mutations of PTEN that turn off that suppression role can allow cancer cells to grow unchecked.

For Lee, founder of Ohio States Center for Affordable Nanoengineering of Polymeric Biomedical Devices, producing the gene is the easy part. The synthetic DNA force-fed to donor cells is copied into a new molecule consisting of messenger RNA, which contains the instructions needed to produce a specific protein. Each exosome bubble containing messenger RNA is transformed into a nanoparticle ready for transport, with no blood-brain barrier to worry about.

The testing in mice showed the labelled exosomes were far more likely to travel to the brain tumours and slow their growth compared to substances used as controls.

Because of exosomes safe access to the brain, Lee said, this drug-delivery system has promise for future applications in neurological diseases such as Alzheimers and Parkinsons disease.

The rest is here:
Mother Nature provides new gene therapy strategy to reverse disease - Health Europa

Inside each of our cells is a genetic hourglass. Every time our cells dividewhich they have to do to keep us alivetheir 23 pairs of chromosomes remain nearly identical. Except for one intentional change: After each division, a cells chromosomes get a little bit shorter.

Ten years ago, a group of scientists won the Nobel Prize in medicine for discovering these ever-shortening DNA sequences at the end of our chromosomes, called telomeres. After a cell has divided a certain number of timesknown as the Hayflick limitits telomeres are so short that the cell knows its time to peacefully shut itself down. When enough cells die off, organs wear out, and eventually, we die, too.

This discovery ushered in decades of aspirational research that set out to understand the role of telomeresand the protein that can rebuild them, called telomerasein aging. Perhaps, if scientists could figure out how to flip our biological hourglasses over, our cells could replicate for longer. Our organs would tire more slowly, and we could delay death.

The Nobel-winning research began way back in the 1970s with the work of biologist Elizabeth Blackburn. But even after four decades, its still not clear if telomeres can safely be manipulated to thwart aging.

That hasnt stopped some scientists from betting on artificially extending telomeres to support longevity: Just last week, Kansas-based biotech startup Libella Gene Therapeutics announced that it would begin early clinical trials testing out a gene therapy that could lengthen telomeres, according to OneZero.

That approach, which as of yet has only been tested in mice, is indicative of humans deep desire to roll back the clock. But the deeper scientists go into the field, the more complicated the story behind telomeres gets: Theres evidence that they may play an important role in other aspects of our health, and that cell division may not be the only reason they shrink over time. Before scientists can try to safely harness telomeres to improve our health, theyll have to answer these questions.

One anti-aging strategy that researchers have investigated involves telomerase, the telomere-building protein that Blackburns colleague Carol Greider discovered on Christmas Day in 1984.

Telomerase is an important tool for cells that divide frequentlylike blood cells, the lining of our digestive systems, or sperm and egg cells. These cells regenerate so often that they need an enzyme to regularly rebuild the caps on the end of their chromosomes.

All the other kinds of cells in our bodies shouldnt have telomerase. But if they did, theoretically, their telomeres would never shrink. They could keep dividing beyond their normal Hayflick limit.

Theres one big problem, though: Cells that have telomerase but arent supposed to often wind up to be cancerous.

In approximately 90% to 95% of cancers, during the process of oncogenesis, telomerase is reactivated, says Masood Shammas, a lead scientist at the Dana Farber Cancer Institute in Boston. As cancer cells spread, theyre able to build their telomeres back upallowing them to keep dividing and dividing and dividing.

This means that messing with telomerase to somehow extend lifeas Libella is attempting to, by injecting patients with a virus containing the gene that codes for telomeraseis risky business.

On the other hand, it also means that blocking telomerase could be a way to treat cancer. Shammas has worked on clinical trials that have tested telomerase-targeting drugs with a company called Geron. Although their original drug worked in mouse models, it failed in early-stage clinical trials for people, because it had some nasty side effects. As a result, scientists have had to put stopping telomerase on hold until they can figure out how to make it only work in cancer cells.

An alternative strategy focuses not on rebuilding telomeres, but slowing their shrinkage in the first place. Scientists are trying to understand what, in addition to normal cell division, causes telomeres to contract. Maybe limiting these activities could decelerate aging in a way that doesnt accidentally reactivate a cancer pathway.

The activities that can slow telomere degradation are still being researched. It seems, though, that theres a lot of daily living that may play a role in telomere length. Anything that damages DNA will damage telomeres, says Shammas.

Telomeres are particularly vulnerable because theyre more exposed on the ends of the chromosomes. Smoking, drinking, and eating red meats fried in oilswhich all produce molecules that can bind to and distort DNAmay harm your telomeres, too. They also happen to all be known carcinogens.

Of course, this doesnt mean their effects are felt immediately, or that these activities will definitely lead to telomere shortening or cancer. Its their cumulative effect over a lifetime, plus other factors that scientists havent nailed down yet, that we need to watch out for. And clinicians generally advise against these activities anyway.

Perhaps more surprisingly, a life-affirming action may also cause telomeres to shrink: Pregnancy.

Dan Eisenberg, a biological anthropologist at the University of Washington, has studied how telomeres behave over time for people who become pregnant. A large cohort study he and his team published last year looked at women in the Philippines. After controlling for age, they found that the more times someone had been pregnant, the shorter their telomeres were. Each pregnancy seemed to shorten a persons telomeres by the equivalent of as many as four years of life.

This could be because of how taxing pregnancy can be on the body. Developing a fetus takes about twice the energy a person normally uses. Theres less energy available to maintain and repair cells for the long-term, Eisenberg says.

While it seems counterintuitive that evolution would penalize a person for reproducing, it may be a necessary trade-off. Perhaps the benefit of spreading new genes into the world is worth the cost of slightly shorter telomeres, Eisenberg explained. After all, evolution doesnt affect the processes that happen to us after we after our reproductive years. Weve already achieved the goal of immortality by way of our progeny.

So, lifestyle modifications to prevent telomere shortening dont sound too appealing. And so far, the only activity that researchers have found that can naturally extend telomeres in the slightest may be exercise. The only thing that world show that can activate telomerase activity is regular exercise, says Shammas. But its still not clear why this is the case, and it certainly doesnt mean that hitting the gym can stave off all aging.

Which brings us back to the promises made by companies like Libella, the gene therapy outfit currently promoting a telomere therapy. With four decades of telomere research yet to produce better guidance than cut down on red meat and exercise more, its easy to appeal to the insecurities and fears of the aging population with less-than-fully-baked treatments.

As OneZero reported, Libellas study is slated to begin early next year in Colombia. Likely, its running there to skirt the US Food and Drug Administrations (FDA) requirement for an Institutional Review Board, which ensures the safety of clinical research participants. Generally, clinical trials overseen by the FDA have been preceded by trials in at least two animal species to show theyre safe and effective. So far, the studies that have backed Libellas gene therapy are based just in mice.

This study has caused a lot of experts to raise eyebrows, particularly when it comes to the ethical issue of asking participants to pay for a therapy with high risks. The company is charging $1 million for each of its five aging but otherwise healthy participants, as well as five participants who have Alzheimers disease and five who have a form of artery disease.

But the trial also raises the question of whether aging itself is a disease worth treating. With any disease, there has to be a disease-free state, says Suresh Rattan, biogerontologist at Aarhus University. In the case of a situation like aging whose main cause is life itself, when will we say that we have treated it? Evolution didnt design us to live forever.

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Science is still studying how telomeres are linked to longevity - Quartz

Gene therapy is providing unprecedented hope for growing numbers of patients and families. This game changer in medicine restores vision in babies born with congenital blindness, reconstitutes defences against infection in inherited immunodeficiencies and offers the perspective of curing the devastating neuromuscular disease, spinal muscular atrophy.

Gene therapy is also removing the need for repeat blood transfusions in adolescents with the inherited blood disorder, beta-thalassemia. Meanwhile, in oncology, CAR-T therapies, involving genetic modifications of a patients own immune cells, are proving life-saving for children or adults with certain types of blood cancers.

All these revolutionary treatments are now approved by regulatory agencies in Europe or the US. Unfortunately, they carry astronomical price tags which prevent their effective delivery to patients. As one case in point, Bluebird Bios Zynteglo for treating beta-thalassemia, has a list price of 1.57 million.

Can high prices be justified?

Gene therapy manufacturers defend their prices by pointing to high development and manufacturing costs, small markets, and unique therapeutic effectiveness as compared to the current standard of care. However, R&D costs are kept secret, and higher numbers of patients eligible for a given therapy do not translate into lower prices.

Indeed, several arguments the manufacturers put forward are dubious or even far-fetched. As of today, claims that a single administration of a gene therapy product will ensure a lifelong cure are simply not supported by the scientific evidence.

Likewise, value-based pricing is often misconceived. As stated by the US Institute for Clinical and Economic Review in its 2017 white paper on gene therapy, the established value of a treatment reflects the maximum price society might be prepared to pay for it - but should not dictate the price that is actually paid. In an ideal world, actual prices should provide market-consistent returns for shareholders and sufficient incentive to innovate.

The EU, a pioneer in gene therapy

European scientists, institutions and charities have been central to the development of gene therapy. The world's first successful clinical trial was reported in 2000 by Alain Fischer and his team at Necker Hospital in Paris, while the first authorisation of a gene therapy product in a regulated market was granted by the European Medicines Agency in 2012.

According to the Cordis database of EU-supported research, 86 gene therapy projects for rare diseases had funding from the European Commission during the FP7 (2007-2013) and Horizon 2020 (2014-2020) research programmes. One can estimate that overall more than 1 billion has been invested in this area by the EU Commission, member states and not-for-profit organisations.

To ensure European patients benefit from these achievements and investments, it is essential to ensure reasonable pricing of gene therapies. Laudable efforts are currently being made by the World Health Organization to increase transparency, and by some member states to join forces in negotiating prices, but such initiatives are unlikely to solve the current crisis as they do not address its root, namely that the sole objective of most gene therapy companies is to maximise the return on investment and shareholder value.

A way forward: enforcing the corporate social responsibility of gene therapy manufacturers

As I recently argued with Alain Fischer and the economist Mathias Dewatripont in the journal Nature Medicine (November 25, 2019), now is the time to reflect on how to enforce the corporate social responsibility of gene therapy companies.

Among the measures we would like to see considered are the insertion of clauses into technology transfer agreements made between academic organisations receiving grants from the European Commission and for-profit companies to make reasonable pricing compulsory.

We also propose to make reimbursement of gene therapies by EU healthcare payers conditional on the companies which are commercialising these products being certified for their corporate social responsibility. This is in line with several commitments made recently by pharma companies. For example, in August 2019, the CEOs of US-based pharma companies signed the Business Roundtable Statement, affirming their commitment to generate value for all their stakeholders not just their shareholders.

Also in August, Novartis announced it had joined the Value Balancing Alliance, a body whose goal is to increase transparency around business decisions, work with external bodies to develop accounting frameworks, and shift priority from profit maximisation to optimising value creation.

Earlier this year, the pharmaceutical company Chiesi was certified as a Benefit Corporation, meaning its legally defined goals include positive social impact in addition to profit.

Of course, the effective implementation of such commitments and their translation into reasonable pricing policies will require both incentives and regulatory controls. The starting point should be a renewed multi-stakeholder conversation with industry, investors, regulators, payers and, of course, patients.

Professor Michel Goldman is Co-director of the I3h Institute at the Universit Libre de Bruxelles and former Executive Director of the EU Innovative Medicines Initiative.

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Viewpoint: EU should take a lead in enforcing the corporate social responsibility of gene therapy manufacturers - Science Business

RESEARCH TRIANGLE PARK AskBio, a gene therapy company based in RTP that recently raised $225 million from investors, will pay up to $240 million in upfront and milestone payments for a license to use gene therapy technology from Massachusetts-based Selecta Biosciences as part of a regime to treat Pompe disease.

The license is for ImmTOR, what Selecta describes as a immune tolerance platform. The technology is addressing barriers to repeat administration of gene therapies.

Pompe disease affects between 5,000 and 10,000 people a year, affectingventilator, cardiac and skeletal muscles and can cause motor neuron dysfunction, with effects on cognition, hearing, speech and fine motor skills, AskBio says.

There is a demonstrated unmet medical need for better treatment approaches for Pompe disease, and this collaboration will enable us to effectively advance our Pompe program with the added benefit of Selectas ImmTOR technology, said Sheila Mikhail, CEO and co-founder of AskBio, in a statement. The opportunity to re-treat patients holds significant promise, and we are pleased to be able to leverage our relationship with Selecta and apply the ImmTOR technology to potentially overcome the challenges associated with re-administering systemic AAV gene therapies.

The companies initially announced a partnership in August.

AskBio gets $235 million in gene therapy support

RTP-based AskBio expands gene therapy target list with acquisition of Scottish biotech

AskBio acquires nano drug delivery tech company RoverMed (+ video: how process works)

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Triangle-based AskBio to pay up to $240M for rights to use gene therapy technology - WRAL Tech Wire

XconomyBoston

Ring Therapeutics, a Flagship Pioneering spinout, launched Thursday with ambitious plans to expand the universe of vectors available for gene therapy delivery.

Gene therapy, treatments intended to treat disease by inserting a gene instead of using drugs or surgery, has had a banner year, with the second ever such therapy approved this year in the US.

Ring want to use itsresearch into viruses that exist in the human body without apparent negative effects to provide more and better options to fuel the rise of gene therapy treatments.

For the past two years, Flagship Pioneering partner and Rings founding CEO Avak Kahvejian says the company has been exploring the human commensal viromebasically, a group of viruses that exist within humans without negative effectsfor its potential to address limitations of the vectors currently used.

The sector relies heavily on adeno-associated viruses (AAVs), which naturally infect humans but arent known to cause disease, to deliver the DNA. Previous exposure, however, can spark an immune response.

A lot of the workhouses in gene therapy have either been pathogenic viruses or viruses that have been taken from other species or viruses that are highly immunogenic, or all of the above, Kahvejian tells Xconomy. That leads to a certain number of limitations, despite the successes and advances weve made to date.

A number of issues stymie widespread use of AAVs, Kahvejian says, including the fact that 10 percent to 20 percent of people have at one time or another been infected with such a virus, thereby building up an immune response to it. Another concern is where such gene therapies end up, because viruses tend to gravitate toward certain types of tissues, and to go elsewhere, require special tweaking.

The Cambridge, MA-based startup believes the viruses it has found are unlikely to cause an immune response or prove pathogenic, given their ubiquity in the body.

Like extrachromosomal DNAa new discovery at least one company is exploring for its potential as a target in cancer treatmentsthe viral sequencing Ring is studying are circular pieces of DNA that exist outside the 23 chromosomes of the human genome.

Ring says it has found thousands of these viruses that coexist with our immune system. It aims to use those to develop vectors that can facilitate gene replacement throughout the bodymultiple times, if necessary. While gene therapy is thought of as a one-time fix, cell turnover means whatever the fix engendered by the inserted gene could falter over time, necessitating a re-up.

Kahvejian wouldnt share a timeline for Rings plan to develop re-dosable, tissue-targeted treatments.

Were looking at the unique features and activities of these viruses in different tissues to establish the various vectors were going to pursue, he said.

Flagship, which pursues scientific questions in-house and builds and funds companies around the answershas put $50 million toward Ring, which has about 30 employees.

Rings president is Rahul Singhvi, an operating partner at Flagship. Most recently he was chief operating officer of Takedas global vaccine business unit. Its head of R&D is Roger Hajjar, who has led gene therapy trials in patients with heart failure.

Ring is the second startup Flagship has spun out this month. Cellarity launched last week.

Sarah de Crescenzo is an Xconomy editor based in San Diego. You can reach her at sdecrescenzo@xconomy.com.

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Ring Therapeutics Launches to Expand Gene Therapy Viral Vector Options - Xconomy

By Dan Ross

Earlier this month, researchers out of the University of Pennsylvania published a breakthrough study which identified several biomarkers associated with shockwave therapy. This study is the first of its kind to identify a possible biological signal revealing shockwave usagean important development for a therapy that leaves no visible trace, but one that has historically generated welfare concerns due to its analgesic effects.

Because its not a drugits applied to the surface of the skinits just not an easy thing to detect, said lead researcher Mary Robinson, assistant professor of veterinary pharmacology and director of the Equine Pharmacology Laboratory at the University of Pennsylvania School of Veterinary Medicine, in a press release. After a lot of trial and error, our study was able to measure changes in levels of five inflammatory factors, some of which we could detect up to three weeks after the shockwave therapy.

The study was conducted on ostensibly healthy horses. Robinson told the TDN that she and her colleagues will continue to research these biomarkers on other populations of racehorses, including injured horses, injured horses that have received shockwave therapy, and healthy horses in training. For this next step, researchers will dip into the universitys large BioBank library of biological samples.

Robinson was also a co-author on a paper published in November proving proof of principle, she said, that they were able to detect experimental gene therapy which had been administered via intra-articular injection. Gene doping and its performance enhancing potential is an emerging problem in horse racing. Broadly speaking, the term refers to the twin practices of gene editingchanging animal DNA before theyre bornand gene therapy, which refers to the implantation of a piece of DNA into an adult animal to prevent or treat a disease or disorder.

In the following Q&A, Robinson discusses shockwave usage, the implications of her shockwave biomarker study, and her ongoing work in gene doping.

TDN: Can you discuss how the shockwave study was conducted?

MR: The study that was just published is looking at the effect of giving a single dose of shockwave to the front of the cannon bone to 11 healthy horses. Whats really novel about this study is we could find changes in the blood that were reflective of these horses receiving shockwave therapy. The biobank is for the next stepsthis initial study was more a proof of concept study.

Essentially, what we did, a week before shockwave was given, we took samples each day. After we gave the dose of shockwave, we then collected samples after that dose for up to three weeks. And we were able to see these changes occurring very rapidly, within 24 hours after the shockwave dose, and some of them lasted for up to three weeks.

What that tells me is we probably will need to follow horses out over time. And so, for each individual animal, in order to make these biomarkers make sense, were going to need to know what their normal profile looks like, and then follow that out over time.

TDN: How did you end up narrowing in on those 10 select biomarkers (of which five indicated shockwave usage)?

MR: That was more a resource limitation than anything else. Its very difficult to do these types of studies on horses, and that maybe speaks to some of the challenges we face in identifying biomarkers. One of the difficult things is there just arent the resources out there.

One of the ways we narrowed in on those 10 was to see which pro-inflammatory and anti-inflammatory proteins were similar between horses and humans, so that we might be able to use the resources available for humans to try to measure these things in horses. We spent quite a lot of time validating the methods that were used to make sure they would work for horses. And we chose pro and anti-inflammatory factors because we know shockwave causes a very acute inflammatory response. It increases the blood flow to the area.

TDN: Whats next in your research?

MR: As you mention, these were healthy horsesthey did not have an injury. And were looking at anti-inflammatory factors which you would maybe expect to be affected by an injury. We need to be able to look at what the effect of an injury is going to do to these factors, and then we need to look at what the effect of giving shockwave on top of that injury is going to do to those factors.

These horses were healthy, but they were not in any type of exercise regimen, so we also need to assess the effect of exercise on these factorsits well documented that [biomarker] IL-6 that we identified is affected by exercise. So, well need to make sure that we take that into account.

TDN: When will you start?

MR: Weve already started. Weve been working on collecting these BioBank samples for several years now. It was just in the last year and a half that weve been able to quadruple the number of samples that weve collected because of the funding from the Horse Breeders Association. Within the next year, were going to be starting to make some comparisons using the markers that weve now identified.

TDN: What can you tell us about the BioBank?

MR: The funding for the BioBank is from the Pennsylvania Horse Breeders Association. I was able to start the bank using some internal funds from the [University of Pennsylvania School of Veterinary Medicine] New Bolton Center, and then the PHBA very generously donated money for us to expand the bank, which allowed us to hire an additional person, and get some more freezers, so that we can collect samples from horses at the racetrack and in training at various training facilities.

TDN: The BioBank primarily contains Thoroughbred samples, right?

MR: Yes, although were actually going to be meeting with some other groups from the Standardbred industry to see if they would be interested in supporting it as well.

TDN: How soon before you possibly narrow in on certain shockwave biomarkers that can be used for regulatory purposes?

MR: I dont know that well ever be able to conclusively prove that shockwave had been administered. I think what we hope to do is identify instead biomarkers that suggest that theres something concerning going on in an individual horse. Whether those relate specifically to shockwave or whether those relate to a horse that has some underlying injurythat somebodys trying to cover up or somebody doesnt even know existsthats what this biological passporthopes to do.

TDN: What are your general thoughts about shockwave usage for horses in training?

MR: Currently in Pennsylvania, we dont allow it on the backside of any of the tracks, and that really is because its not something that we can detect currently. We do not want to have it risked being used too close to a race, and thats a problem with shockwave: it has a very strong analgesic effect, just as effective as the nerve block when its used on an injury. The key is, it can be used as a therapeutic, but you have to absolutely rest the horse. You cannot run the horse shortly after its received shockwave.

TDN: Do you agree with the Association of Racing Commissioners Internationals model rule requiring a 10-day stand-down, given what we currently know about the analgesic effect?

MR: I do. But theres only one study thats definitively shown that theres an analgesic affect. I think that they stopped around two days in that study, and its not really clear whether that effect would have lasted longer or not. Theres potential that it could have an analgesic effect for a longer period of time.

TDN: What are the implications of gene doping for horse racing?

MR: Its another new way to treat disease. Instead of having to give multiple doses, the whole point of gene therapy is you can give a single dose and have a more permanent treatment. So, when you think of it in that regard, the potential for using it illicitly to try to enhance performance is huge, because a single dose might be able to create a lasting effect. So, I do think its a serious concern. Its been on the WADA [World Anti-Doping Agency] anti-doping list since 2003. So, our human colleagues have certainly been concerned about it for quite some time.

TDN: Do things that go on in human athletics often makes their way into horse racing?

MR: We certainly have seen that pattern, although the reverse is possible. Some people may feel more comfortable experimenting with horses than with humans. Of course, cost always becomes an issue. But its possible there are people with the means who are willing to try and win at all costs. So, thats what were trying to prevent.

TDN: How big an issue is it currently for horse racing?

MR: Its really hard to know at this point. There certainly has been suspicion and discussion and talk about it. I have to say I was pretty skeptical that this was a problem until more recently. Now that the therapies are being approved in humans, theyve accelerated the ability for people to actually develop these therapies, so, I think its something we need to address as soon as possible as an industry.

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Q&A: UPenn's Mary Robinson Talks Shockwave and Gene Doping - Thoroughbred Daily News

DetailsCategory: More NewsPublished on Friday, 20 December 2019 13:54Hits: 103

Selecta eligible to receive upfront and milestone payments of over $240 million

AskBios AAV gene therapy combined with ImmTOR could prevent the formation of neutralizing antibodies and potentially enable re-treatment of patients with Pompe disease

WATERTOWN, MA and RESEARCH TRIANGLE PARK, NC, USA I December 19, 2019 ISelecta Biosciences, Inc. (NASDAQ: SELB) and Asklepios BioPharmaceutical, Inc. (AskBio), today announced that the companies have entered into a license agreement. Under the terms of the agreement, AskBio has exercised its option to exclusively license rights to develop and commercialize Selectas immune tolerance platform, ImmTOR, for use in adeno-associated virus (AAV) gene therapy for the treatment of Pompe disease. When used in combination with AAV gene therapy vectors, Selectas ImmTOR has been shown to inhibit the immune response to the vector (Nature Communications, October 2018).

Selecta and AskBio previously announced a strategic partnership in August 2019 to jointly develop, manufacture, and commercialize targeted therapeutics for next-generation AAV gene therapies in areas of high medical need. Under the terms of this new license agreement, Selecta is eligible to receive upfront and milestone payments of over $240 million plus royalties on product sales.

We are pleased to advance our ImmTOR platform in a new partnership with AskBio for Pompe disease, a serious and progressively debilitating disease, said Carsten Brunn, Ph.D., President and Chief Executive Officer of Selecta. We are excited to collaborate with AskBio to potentially enable the retreatment of AAV gene therapies.

There is a demonstrated unmet medical need for better treatment approaches for Pompe disease, and this collaboration will enable us to effectively advance our Pompe program with the added benefit of Selectas ImmTOR technology, said Sheila Mikhail, CEO and co-founder of AskBio. The opportunity to re-treat patients holds significant promise, and we are pleased to be able to leverage our relationship with Selecta and apply the ImmTOR technology to potentially overcome the challenges associated with re-administering systemic AAV gene therapies.

Pompe disease is a rare, progressive, debilitating condition that affects 5,000 to 10,000 people worldwide. It impacts ventilator, cardiac and skeletal muscles and can cause motor neuron dysfunction, with effects on cognition, hearing, speech and fine motor skills. Pompe disease can manifest any time between infancy and late adulthood and may have differing symptoms and severity, depending on when it develops. There is a substantial unmet medical need for more efficient and effective treatments for Pompe disease. Currently, the only approved treatment is ERT with recombinant human GAA (rhGAA), a chronically administered therapy requiring increasing doses, which can elevate both costs and treatment burden.

AboutSelecta Biosciences, Inc. Selecta Biosciences, Inc.is a clinical-stage biotechnology company focused on unlocking the full potential of biologic therapies based on its immune tolerance technology (ImmTOR) platform.Selectaplans to combine ImmTOR with a range of biologic therapies for rare and serious diseases that require new treatment options due to high immunogenicity. The companys current proprietary pipeline includes ImmTOR-powered therapeutic enzyme and gene therapy product candidates. SEL-212, the companys lead product candidate, is being developed to treat chronic refractory gout patients and resolve their debilitating symptoms, including flares and gouty arthritis. Selectas proprietary gene therapy product candidates are in preclinical development for certain rare inborn errors of metabolism and incorporate ImmTOR with the goal of addressing barriers to repeat administration.Selectais based inWatertown, Massachusetts. For more information, please visithttp://selectabio.com.

About AskBioFounded in 2001, Asklepios BioPharmaceutical, Inc. (AskBio) is a privately held, clinical-stage gene therapy platform company dedicated to improving the lives of children and adults with genetic disorders. AskBios gene therapy platform includes an industry-leading proprietary cell line manufacturing process known as Pro10 and an extensive AAV capsid library. Based in Research Triangle Park, North Carolina, the company has generated hundreds of proprietary third-generation gene vectors, several of which have entered clinical testing. An early innovator in the space, the company holds more than 500 patents in areas such as AAV production, chimeric vectors and self-complementary DNA. AskBio maintains a portfolio of clinical programs across a range of neurodegenerative and neuromuscular indications with a current clinical pipeline that includes therapeutics for Pompe disease, limb-girdle muscular dystrophy and congestive heart failure, as well as out-licensed clinical indications for hemophilia (Chatham Therapeutics acquired by Takeda) and Duchenne muscular dystrophy (Bamboo Therapeutics acquired by Pfizer). For more information, visit https://www.askbio.com/.

About Pompe DiseasePompe disease is an inherited lysosomal storage disorder caused by deficiency of the enzyme acid alpha-glucosidase (GAA). Reduced or absent levels of GAA lead to accumulation of glycogen in cells, which is believed to result in the clinical manifestations of Pompe disease. The disease can be debilitating and is characterized by severe muscle weakness that worsens over time. Pompe disease ranges from a rapidly fatal infantile form with significant impacts to heart function, to a more slowly progressive, late-onset form primarily affecting skeletal muscle. It is estimated that Pompe disease affects approximately 5,000 to 10,000 people worldwide.

SOURCE: AskBio

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AskBio Licenses Rights to Selecta Biosciences' ImmTOR Immune Tolerance Platform for the Treatment of Pompe Disease | More News | News Channels -...