Archive for October, 2019

DUBLIN--(BUSINESS WIRE)--The "Cell Therapy - Technologies, Markets and Companies" report from Jain PharmaBiotech has been added to ResearchAndMarkets.com's offering.

This report describes and evaluates cell therapy technologies and methods, which have already started to play an important role in the practice of medicine. Hematopoietic stem cell transplantation is replacing the old fashioned bone marrow transplants. The role of cells in drug discovery is also described. Cell therapy is bound to become a part of medical practice.

Stem cells are discussed in detail in one chapter. Some light is thrown on the current controversy of embryonic sources of stem cells and comparison with adult sources. Other sources of stem cells such as the placenta, cord blood and fat removed by liposuction are also discussed. Stem cells can also be genetically modified prior to transplantation.

Cell therapy technologies overlap with those of gene therapy, cancer vaccines, drug delivery, tissue engineering and regenerative medicine. Pharmaceutical applications of stem cells including those in drug discovery are also described. Various types of cells used, methods of preparation and culture, encapsulation and genetic engineering of cells are discussed. Sources of cells, both human and animal (xenotransplantation) are discussed. Methods of delivery of cell therapy range from injections to surgical implantation using special devices.

Cell therapy has applications in a large number of disorders. The most important are diseases of the nervous system and cancer which are the topics for separate chapters. Other applications include cardiac disorders (myocardial infarction and heart failure), diabetes mellitus, diseases of bones and joints, genetic disorders, and wounds of the skin and soft tissues.

Regulatory and ethical issues involving cell therapy are important and are discussed. The current political debate on the use of stem cells from embryonic sources (hESCs) is also presented. Safety is an essential consideration of any new therapy and regulations for cell therapy are those for biological preparations.

The cell-based markets was analyzed for 2018 and projected to 2028. The markets are analyzed according to therapeutic categories, technologies, and geographical areas. The largest expansion will be in diseases of the central nervous system, cancer, and cardiovascular disorders. Skin and soft tissue repair, as well as diabetes mellitus, will be other major markets.

The report contains information on the following:

Key Topics Covered:

Part I: Technologies, Ethics & Regulations

Executive Summary

1. Introduction to Cell Therapy

2. Cell Therapy Technologies

3. Stem Cells

4. Clinical Applications of Cell Therapy

5. Cell Therapy for Cardiovascular Disorders

6. Cell Therapy for Cancer.

7. Cell Therapy for Neurological Disorders

8. Ethical, Legal and Political Aspects of Cell therapy

9. Safety and Regulatory Aspects of Cell Therapy

Part II: Markets, Companies & Academic Institutions

10. Markets and Future Prospects for Cell Therapy

11. Companies Involved in Cell Therapy

12. Academic Institutions

13. References

For more information about this report visit https://www.researchandmarkets.com/r/9q5tz1

See more here:
Global Cell Therapy Technologies, Companies & Markets During the Forecast Period, 2018-2028 - ResearchAndMarkets.com - Business Wire

PENSACOLA, Fla. (WKRG) Osteoarthritis affects millions of people in the US. Symptoms range from minor pain to crippling pain that compromises quality of life. A groundbreaking study is underway at four prestigious research facilities in the United States. One of those is right here on the Gulf Coast. Tonight, Drexel Gilbert is on the road in Gulf Breeze.

Lori Jamison is a Pensacola native who, as a teenager, played basketball at Pine Forest High School. Today, she suffers from osteoarthritis in her knee. She believes its a result of basketball injuries.

I get stiffness, it interferes with my mobility. Sometimes its like a sharp needle going down your leg. When I go to the movie theater, I have to sit on the back row so I can stretch it out, Jamison said. She is participating in a clinical trial at Andrews Research and Education Foundation in Gulf Breeze.

The research is studying stem cell treatment for osteoarthritis in the knee. AREF is one of only four facilities in the country participating in the study. The others are Emory Orthopedics & Spine Center, Duke University and Sanford Health. Researchers hope it leads to FDA approval for the treatment. If that happens, it could be life-changing for patients.

Hopefully reduce their pain if not actually get rid of their pain. That is our goal. We want to delay, if not prevent, total knee replacement, said Dr. Josh Hackel, who is the primary investigator for the Andrews phase of the study. Were comparing three different stem cell sources. Bone marrow from their pelvis, adipose- thats tissue from their belly fat- and the third is umbilical cord tissue donated from pregnant mothers.

The bone marrow and belly fat stem cells are harvested from the study participants, under local anesthesia. The stem cells are later implanted into the knee joint using ultrasound guidance to implant the cells into the knee joint.

Jamison has already undergone stem cell harvesting.

It was very easy, very convenient, no downtime after the procedure was done, Jamison said

This $13 million clinical trial is being funded entirely by a grant from Bernie Marcus, founder of the Marcus Foundation and co-founder of Home Depot. Osteoarthritis is an issue that is close to the philanthropists heart because his mother was left disabled by the illness at a young age.

There will be around 120 participants at each of the four sites. There are plenty of openings. If youd like to be considered for the study, call AREF at 850-916-8591.

Read the rest here:
Drexel on the Road: Stem cell study for osteoarthritis - WKRG News 5

This article, written byKatharine Sedivy-Haley, University of British Columbia, originally appeared on The Conversation and is republished here with permission:

When I was applying to graduate school in 2012, it felt like stem cells were about to revolutionize medicine.

Stem cells have the ability to renew themselves, and mature into specialized cells like heart or brain cells. This allows them to multiply and repair damage.

If stem cell genes are edited to fix defects causing diseases like anemia or immune deficiency, healthy cells can theoretically be reintroduced into a patient, thereby eliminating or preventing a disease. If these stem cells are taken or made from the patient themselves, they are a perfect genetic match for that individual, which means their body will not reject the tissue transplant.

Because of this potential, I was excited that my PhD project at the University of British Columbia gave me the opportunity to work with stem cells.

However, stem cell hype has led some to pay thousands of dollars on advertised stem cell treatments that promise to cure ailments from arthritis to Parkinsons disease. These treatments often dont help and may harm patients.

Despite the potential for stem cells to improve medicine, there are many challenges as they move from lab to clinic. In general, stem cell treatment requires we have a good understanding of stem cell types and how they mature. We also need stem cell culturing methods that will reliably produce large quantities of pure cells. And we need to figure out the correct cell dose and deliver it to the right part of the body.

Embryonic, 'induced and pluripotent

Stem cells come in multiple types. Embryonic stem cells come from embryos which makes them controversial to obtain.

A newly discovered stem cell type is the induced pluripotent stem cell. These cells are created by collecting adult cells, such as skin cells, and reprogramming them by inserting control genes which activate or induce a state similar to embryonic stem cells. This embryo-like state of having the versatile potential to turn into any adult cell type, is called being pluripotent.

However, induced pluripotent and embryonic stem cells can form tumours. Induced pluripotent stem cells carry a particularly high risk of harmful mutation and cancer because of their genetic instability and changes introduced during reprogramming.

Genetic damage could be avoided by using younger tissues such as umbilical cord blood, avoiding tissues that might contain pre-existing mutations (like sun-damaged skin cells), and using better methods for reprogramming.

Stem cells used to test drugs

For now, safety concerns mean pluripotent cells have barely made it to the clinic, but they have been used to test drugs.

For drug research, it is valuable yet often difficult to get research samples with specific disease-causing mutations; for example, brain cells from people with amyotrophic lateral sclerosis (ALS).

Researchers can, however, take a skin cell sample from a patient, create an induced pluripotent stem-cell line with their mutation and then make neurons out of those stem cells. This provides a renewable source of cells affected by the disease.

This approach could also be used for personalized medicine, testing how a particular patient will respond to different drugs for conditions like heart disease.

Vision loss from fat stem cells

Stem cells can also be found in adults. While embryonic stem cells can turn into any cell in the body, aside from rare newly discovered exceptions, adult stem cells mostly turn into a subset of mature adult cells.

For example, hematopoietic stem cells in blood and bone marrow can turn into any blood cell and are widely used in treating certain cancers and blood disorders.

A major challenge with adult stem cells is getting the right kind of stem cell in useful quantities. This is particularly difficult with eye and nerve cells. Most research is done with accessible stem cell types, like stem cells from fat.

Fat stem cells are also used in stem cell clinics without proper oversight or safety testing. Three patients experienced severe vision loss after having these cells injected into their eyes. There is little evidence that fat stem cells can turn into retinal cells.

Clinical complications

Currently, stem cell based treatments are still mostly experimental, and while some results are encouraging, several clinical trials have failed.

In the brain, despite progress in developing treatment for genetic disorders and spinal cord injury, treatments for stroke have been unsuccessful. Results might depend on method of stem cell delivery, timing of treatment and age and health of the patient. Frustratingly, older and sicker tissues may be more resistant to treatment.

For eye conditions, a treatment using adult stem cells to treat corneal injuries has recently been approved. A treatment for macular degeneration using cells derived from induced pluripotent stem cells is in progress, though it had to be redesigned due to concerns about cancer-causing mutations.

A path of cautious optimism

While scientists have good reason to be interested in stem cells, miracle cures are not right around the corner. There are many questions about how to implement treatments to provide benefit safely.

In some cases, advertised stem cell treatments may not actually use stem cells. Recent research suggests mesenchymal stem cells, which are commonly isolated from fat, are really a mixture of cells. These cells have regenerative properties, but may or may not include actual stem cells. Calling something a stem cell treatment is great marketing, but without regulation patients dont know what theyre getting.

Members of the public (and grad students) are advised to moderate their excitement in favour of cautious optimism.

Katharine Sedivy-Haley, PhD Candidate in Microbiology and Immunology, University of British Columbia

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Read more:
BEYOND LOCAL: Expert recommends 'path of cautious optimism' about the future of stem cell treatment - ElliotLakeToday.com

Jennifer Adair, a senior scientist at Fred Hutch, speaks at the 2019 GeekWire Summit. (GeekWire Photo / Kevin Lisota)

Genetically editing cells using CRISPR could be the answer to curing genetic disorders such as sickle cell anemia. But in order for the technology to be available for people in countries like Nigeria where around a quarter of the population carries the sickle cell trait the technology will need to become substantially cheaper and less invasive.

Thats where gold nanoparticles come in.

Scientists at the Fred Hutchinson Cancer Research Center are devising an approach that vastly simplifies how CRISPR is applied. Their goal is to create a safe process for gene editing that takes place entirely within the body of a patient.

In order to edit human stem cells using CRISPR today, scientists have to follow a process that involves removing the cells from a patients bone marrow, electrocuting those cells, and modifying them with engineered virus particles.

The process gets even more invasive from there. We actually have to treat these patients with chemotherapy, radiation or other agents in order for these cells that were genetically manipulated to be taken up, Jennifer Adair, a senior scientist at Fred Hutch, said during a talk at the 2019 GeekWire Summit.

The researchers think theyve figured out the first step, which is delivering CRISPR to blood stem cells inside the body. Theyre doing that using gold nanoparticles that are about a billionth the size of a grain of table salt and able to smuggle in RNA, DNA and a protein.

Weve been able to show that not only can we make these, but they passively deliver all of those components to blood stem cells, then we do get genetic editing. And weve been able to go on to show that we can correct the sickle cell defect using this approach, said Adair.

The nanoparticles are big enough to carry the CRISPR payload but small enough to infiltrate cell membranes. Gold is a useful medium since it isnt harmful to humans.

The Fred Hutch team published their work with gold nanoparticles earlier this year in the journal Nature Materials. The system safely edited 10 to 20 percent of the target cells, which the researchers hope will increase as the method is refined.

In an ideal world, clinicians would be able to deliver gene therapy through a syringe, a process that might be accomplished in a single office visit. Adair previously published research on agene therapy in a box concept, a table-top device that could provide gene therapy treatments without the need for expensive medical infrastructure.

We need to develop technologies that make gene editing simpler, more affordable and more accessible to patients around the world, Adair said.

Go here to read the rest:
Fred Hutch scientist on how gold nanoparticles could bring CRISPR to the developing world - GeekWire

Stem Cell Therapy Market is expected to reach 202.77 billion by 2026 from 12.25 billion in 2017 at CAGR of 42.02%.(Detailed analysis of the market CAGR is provided in the report) stands for use of stem cells to treat or prevent disease or condition.

Bone marrow transplant and some therapies derived from umbilical cord blood are mainly used in stem cell therapy. Advancement, in order to establish new sources for stem cells, and to apply stem-cell treatments for neurodegenerative diseases and conditions such as diabetes, heart disease, and other conditions, are increased in recent years. Stem Cell Therapy Market Researchers are making efforts to discover novel methods to create human stem cells. This will increase the demand as well as supply for stem cell production and potential investigation in disease management. Increasing investment & research grants for developing safe and effective stem cell therapy products, the growing patient base for target diseases, concentrated product pipelines, increasing approval of the new clinical trials, rapid technological advancement in genomics, and the rising awareness about the stem cell are expected to drive the growth of the Stem Cell Therapy solutions market during the forecast period.

REQUEST FOR FREE SAMPLE REPORT: https://www.maximizemarketresearch.com/request-sample/522

However, improper infrastructure, insufficient storage systems, nascent technology in underdeveloped economies, Ethical issues related to an embryonic stem cell, low patient acceptance rate, Difficulty in the preservation of stem cell are expected to restrain the market growth. North America is expected to be the largest growing region by 2026; the reason behind that is extensive funding by Government. However, Emerging countries like India, china, Korea have low growth rate as compared to Developed regions in 2017 but increase in awareness about stem cell therapy will lead the Asia Pacific to generate a significant level of revenue by 2026.Key Highlights of Stem Cell Therapy Market report

Detailed quantitative analysis of the current and future trends from 2017 to 2026, which helps to identify the prevailing market opportunities.Comprehensive analysis of factors instrumental in changing the market scenario, rising prospective opportunities, market shares, core competencies in terms of market development, growth strategies and identification of key companies that can influence this market on a global and regional scale.Assessment of Market definition along with the identification of key drivers, restraints opportunities and challenges for this market during the forecast period.Complete analysis of micro-markets with respect to individual growth trends, prospects, and contributions to the overall Stem Cell Therapy Solutions market.Stem Cell Therapy market analysis and comprehensive segmentation with respect to the Application, End users, Treatment, and geography to assist in strategic business planning.Stem Cell Therapy market analysis and forecast for five major geographies-North America, Europe, Asia Pacific, Middle East & Africa, Latin America, and their key regions.For company profiles, 2017 has been considered as the base year. In cases, wherein information was unavailable for the base year, the years prior to it have been considered.

Research Methodology:

The market is estimated by triangulation of data points obtained from various sources and feeding them into a simulation model created individually for each market. The data points are obtained from paid and unpaid sources along with paid primary interviews with key opinion leaders (KOLs) in the market. KOLs from both, demand and supply side were considered while conducting interviews to get an unbiased idea of the market. This exercise was done at a country level to get a fair idea of the market in countries considered for this study. Later this country-specific data was accumulated to come up with regional numbers and then arrive at a global market value for the stem cell therapy market.

Key Players in the Stem Cell Therapy Market are:

Chiesi Farmaceutici S.P.A Are:Gamida CellReNeuron Group, plcOsiris Therapeutics, Inc.Stem Cells, Inc.Vericel Corporation.Mesoblast, Ltd.

Key Target Audience:

Stem Cell Associations and OrganizationsGovernment Research Boards and OrganizationsResearch and consulting firmsStem Cell Therapy Market InvestorsHealthcare Service Providers (including Hospitals and Diagnostic Centers)Stem Cell Therapeutic Product Manufacturing OrganizationsResearch LabsClinical research organizations (CROs)Stem Cell Therapy Marketing PlayersPharmaceutical Product Manufacturing Companies

DO INQUIRY BEFORE PURCHASING REPORT HERE: https://www.maximizemarketresearch.com/inquiry-before-buying/522

Scope of the Stem Cell Therapy Market Report:

Stem Cell Therapy market research report categorizes the Stem Cell Therapy market based on Application, End users, Treatment, and geography (region wise). Market size by value is estimated and forecasted with the revenues of leading companies operating in the Stem Cell Therapy market with key developments in companies and market trends.Stem Cell Therapy Market, By Treatments:

Allogeneic Stem Cell TherapyAutologous Stem Cell Therapy

Stem Cell Therapy Market, By End Users:HospitalsAmbulatory Surgical CentersStem Cell Therapy Market, By Application:OncologyCentral Nervous System DiseasesEye DiseasesMusculoskeletal DiseasesWound & InjuriesMetabolic DisordersCardiovascular DisordersImmune System DisordersStem Cell Therapy Market, By Geography:

North AmericaEuropeAsia PacificMiddle East & AfricaLatin America

Available Customization:

With the given market data, Maximize Market Research offers customization of report and scope of the report as per the requirement

Regional Analysis:

Breakdown of the North America stem cell therapy marketBreakdown of the Europe stem cell therapy marketBreakdown of the Asia Pacific stem cell therapy marketBreakdown of the Middle East & Africa stem cell therapy marketBreakdown of the Latin America stem cell therapy market

MAJOR TOC OF THE REPORT

Chapter One: Stem Cell Therapy Market Overview

Chapter Two: Manufacturers Profiles

Chapter Three: Global Stem Cell Therapy Market Competition, by Players

Chapter Four: Global Stem Cell Therapy Market Size by Regions

Chapter Five: North America Stem Cell Therapy Revenue by Countries

Chapter Six: Europe Stem Cell Therapy Revenue by Countries

Chapter Seven: Asia-Pacific Stem Cell Therapy Revenue by Countries

Chapter Eight: South America Stem Cell Therapy Revenue by Countries

Chapter Nine: Middle East and Africa Revenue Stem Cell Therapy by Countries

Chapter Ten: Global Stem Cell Therapy Market Segment by Type

Chapter Eleven: Global Stem Cell Therapy Market Segment by Application

Chapter Twelve: Global Stem Cell Therapy Market Size Forecast (2019-2026)

Browse Full Report with Facts and Figures of Stem Cell Therapy Market Report at: https://www.maximizemarketresearch.com/market-report/stem-cell-therapy-market/522/

About Us:

Maximize Market Research provides B2B and B2C market research on 20,000 high growth emerging technologies & opportunities in Chemical, Healthcare, Pharmaceuticals, Electronics & Communications, Internet of Things, Food and Beverages, Aerospace and Defense and other manufacturing sectors.

Contact info:

Name: Lumawant Godage

Organization: MAXIMIZE MARKET RESEARCH PVT. LTD.

Email: sales@maximizemarketresearch.com

Contact: +919607065656/ +919607195908

Website: http://www.maximizemarketresearch.com

Here is the original post:
Stem Cell Therapy Market by Treatment,Application,End Users and Geography Forecast To 2026 - Weekly Spy

By JLNJ Staff | October 10, 2019

(Courtesy of Ezer Mizion) Flying 35,000 feet above the Atlantic Ocean is not an easy job! But Ofer had already spent 17 years as a fighter pilot in the IDF defending the State of Israel. In 2003 he left the reserves and joined El-Al full time. Most people dont realize that being a pilot is a very dangerous profession. When you know it is dangerous you are safe but when you think it is easy, when youre a cowboy, you are unsafe! A pilots job is to always be alert in case something happens. Ofer always remained alert with hundreds of travelers under his wing, quite literally!

But after 16 years of flying for El-Al, Ofer started to feel fatigued. It became difficult for me to walk up with steps to the plane from the tarmac. I thought I was starting to get old or out of shape. But the truth was far more devastating: after routine blood tests, Ofer was diagnosed with leukemia!

I was immediately rushed to the hospital. When I arrived they couldnt even find bone marrow inside my body for a biopsy. I had very little bone marrow left in my body.

Ofer started to think about his future. He thought, Will I ever be able to fly again? Will I be able to see my children again? Will I get to meet my grandchildren?

It was a very difficult time in my life. I was very lucky to have the best doctors in Israel. Shortly after Jan 1, 2017, Ofer was told that Ezer Mizion had a perfect bone marrow match for him! He was thrilled, but still very hesitant. I knew I was not yet out of the woods. I was on a new medication and I was starting to feel better. I did not know if I wanted to risk a transplant with possible complications. Ofer decided to take a vacation to Moscow. He had always traveled the world and Moscow was one place he had never visited but had always wanted to see. The doctors told me if I get even a small virus I can forget about the whole transplant. I put my faith in God and said, if it is meant to be, then I will return and have the transplant.

On Feb. 28, Ofer landed back in Tel Aviv, and March 1 started his preparations for a transplant.

Pushing through all the negative thoughts, Ofer decided to fight. He was absolutely determined to overcome this illness and would go to any lengths to get better.

A short six weeks later Ofer was released from the hospital and returned to his family.

David Bugoslavski was in the middle of his military service on Mt. Hermon when he received a call from Ezer Mizion that he is a perfect match for a cancer patient. Ironically, David wasnt supposed to have his phone on him while he was in the middle of active duty. Yet, as he explains, fate thought otherwise. He knew that Ezer Mizion needed him, and while he did not know Ofer personally, he jumped at the opportunity to save the pilots life.

Thanks to Davids transplant, Ofer is alive today. While the recovery process is slow and there has been some turbulence along the way, Ofer has his life back. One of Ofers dreams had always been to fly a Boeing Dreamliner. Unfortunately, due to his medical history, this dream will never come to fruition in his capacity as a pilot but he still loves to travel the world, even if hes sitting in the back of the plane.

David was able to jump on a once-in-a-lifetime opportunity to save a life. Ofer was able to be the recipient of a special and unique kindness, having his life literally saved by someone else. As Ofer explained so beautifully, David: without you, I wouldnt be here... For me, you are part of the family.

Ezer Mizions bone marrow registry has close to 1 million registrants, with over 550,000 of them IDF soldiers. At Ezer Mizion, no matter who you are or where you come from, your life matters. Ofer and David are just one example of the lifesaving mission of Ezer Mizion taking flight. At Ezer Mizion, unconditional love is not just a term thrown around, but a philosophy that is in the very DNA of the organization. As Dr. Bracha Zisser, director and founder of Ezer Mizions National Bone Marrow Registry says, We have created a true connection of blood between two people who did not know each other at all up to that point. A connection that would not have happened without the unconditional immediate enlistment of David or, as Ofer called him, my angel.

Join Ezer Mizion on November 9 at Congregation Keter Torah in Teaneck at 7:30 p.m. for an Evening of Heroes: a beautiful musical Havdalah by Shulem Lemmer, meet real IDF heroes who have saved lives by donating their stem cells, and a fireside chat with Bret Stephens and Nachum Segal. Learn more about Ezer Mizion and RSVP for the Evening of Hereos by going to http://www.eveningofheroes.com, or contact Ryan Hyman, national director of development, at [emailprotected] or 718-853-8400 ext.109.

Read more from the original source:
The Connection Deeper Than Blood - Jewish Link of New Jersey

The 2019 Nobel Prize in Medicine awarded for research in cellular responses to oxygen By Benjamin Mateus 10 October 2019

In the course of a lifetime, the human heart will beat more than three billion times. We will have taken more than 670 million breaths before we reach the end of our lives. Yet, these critical events remain unconscious and imperceptible in everyday life, unless we exert ourselves, such as running up several flights of stairs. We quickly tire, stop to take deep breaths and become flushed.

With the deepening comprehension by medical science of how our bodies work, we have come to better understand the fundamental importance of oxygen to life. Every living organism relies on it in one form or another. However, how cells and tissues can monitor and respond to oxygen levels remained difficult to elucidate. It has only been late in the 20th century with advances in cellular biology and scientific instrumentation that these processes have finally been explained.

On Monday, the 2019 Nobel Prize in Physiology or Medicine was awarded jointly to three individuals: William G. Kaelin, Jr., Sir Peter J. Ratcliffe, and Gregg L. Semenza. Specifically, their discoveries helped elucidate the mechanisms for lifes most basic physiologic processes.

They were able to discover how oxygen levels directly affect cellular metabolism, which ultimately controls physiological functions. More importantly, their findings have significant implications for the treatments of conditions as varied as chronic low blood counts, kidney disease, patients with heart attacks or stroke and cancers. One of the hallmarks of cancer is its ability to generate new blood vessels to help sustain its growth. It also uses these oxygen cellular mechanisms to survive in low oxygen environments.

Dr. William G. Kaelin Jr. is a professor of medicine at Harvard University and the Dana-Farber Cancer Institute. The main focus of his work is on studying how mutations in what are called tumor suppressor genes lead to cancer development. Tumor suppressor genes are special segments of the DNA whose function is to check the integrity of the DNA before allowing a copy of itself to be made and undergo cell division, which prevents cells from propagating errors. Cellular mechanisms are then recruited to fix these errors or drive the cell to destroy itself if the damage is too severe or irreparable.

His interest in a rare genetic disorder called Von Hippel-Lindau disease (VHL) led him to discover that cancer cells that lacked the VHL gene expressed abnormally high levels of hypoxia-regulated genes. The protein called the Hypoxia-Inducible Factor (HIF) complex was first discovered in 1995 by Gregg L. Semenza, a co-recipient of the Nobel Prize. This complex is nearly ubiquitous to all oxygen-breathing species.

The function of the HIF complex in a condition of low oxygen concentration is to keep cells from dividing and growing, placing them in a state of rest. However, it also signals the formation of blood vessels, which is important in wound healing as well as promoting the growth of blood vessels in developing embryos. In cancer cells, the HIF complex helps stimulate a process called angiogenesis, the formation of new blood vessels, which allows the cancer cells to access nutrition and process their metabolic waste, aiding in their growth. When the VHL gene is reintroduced back into the cancer cells, the activity of the hypoxia-regulated genes returns to normal.

Dr. Gregg L. Semenza is the founding director of the vascular program at the Johns Hopkins Institute for Cell Engineering. He completed his residency in pediatrics at Duke University Hospital and followed this with a postdoctoral fellowship at Johns Hopkins. His research in biologic adaptations to low oxygen levels led him to study how the production of erythropoietin (EPO) was controlled by oxygen. EPO is a hormone secreted by our kidneys in response to anemia. The secretion of EPO signals our bone marrow to produce more red blood cells.

His cellular and mouse model studies identified a specific DNA segment located next to the EPO gene that seemed to mediate the production of EPO under conditions of low oxygen concentration. He called this DNA segment HIF.

Sir Peter J. Ratcliffe, a physician and scientist, trained as a nephrologist, was head of the Nuffield Department of Clinical Medicine at the University of Oxford until 2016, when he became Clinical Research Director at the Francis Crick Institute. Through his research on the cellular mechanisms of EPO and its interaction between the kidneys and red cell production, he found that these mechanisms for cellular detection of hypoxia, a state of low oxygen concentration, were also present in several other organs such as the spleen and brain. Virtually all tissues could sense oxygen in their micro-environment, and they could be modified to give them oxygen-sensing capabilities.

Dr. Kaelins findings had shown that the protein made by the VHL gene was somehow involved in controlling the response to low oxygen concentrations. Dr. Ratcliffe and his group made the connection through their discovery that the protein made by the VHL gene physically interacts with HIF complex, marking it for degradation at normal oxygen levels.

In 2001, both groups published similar findings that demonstrated cells under normal oxygen levels will attach a small molecular tag to the HIF complex that allows the VHL protein to recognize and bind HIF, marking it for degradation by enzymes. If the oxygen concentration is low, the HIF complex is protected from destruction. It begins to accumulate in the nucleus where it binds to a specific section of the DNA called hypoxia-regulating genes, which sets into motion the necessary mechanisms to respond to the low oxygen concentration.

The ability to sense oxygen plays a vital role in health and various disease states. Patients who suffer from chronic kidney failure also suffer from severe anemia because their ability to produce EPO is limited. This hormone is necessary for the stem cells in our bone marrow to produce red blood cells. Understanding how cancer cells utilize oxygen-sensing mechanisms has led to a variety of treatments that targets these pathways. The ability to elucidate these mechanisms offers insight into directions scientists and researchers can take to design or create novel treatments.

The WSWS recently published its 75,000th article. Become a monthly donor today and keep up this vital work. It only takes a minute. Thank you.

View original post here:
The 2019 Nobel Prize in Medicine awarded for research in cellular responses to oxygen - World Socialist Web Site

DORVAL, QC, Oct. 9, 2019 /CNW/ - Novartis Pharmaceuticals Canada Inc. is pleased to announce that sites in Quebec have been certified in accordance with applicable requirements to treat eligible patients with Kymriah (tisagenlecleucel), the first chimeric antigen receptor T cell (CAR-T) therapy that received regulatory approval in Canada. Patients with relapsed/refractory (r/r) pediatric and young adult B-cell acute lymphoblastic leukemia (ALL) and adult r/r diffuse large B-cell lymphoma (DLBCL) may be eligible to be treated with Kymriah at one of the initially certified Canadian treatment sites. This news coincides with the Quebec government announcement that Kymriah is now reimbursed for eligible patients under the Rgie de l'assurance maladie du Qubec (RAMQ)ii.

Eligible patients in Quebec are now able to access Kymriah from the Centre hospitalier universitaire (CHU) Sainte-Justine and Maisonneuve-Rosemont Hospital (HMR) in Montreal.

"Novartis feels it is important to acknowledge the collaborative effort by all stakeholders involved to ensure Canadians have access to the first approved CAR-T therapy for patients with B-cell ALL and DLBCL who historically have poor outcomes. With treatment centers certified in Quebec, this allows patients with these two life-threatening cancers the opportunity to be treated with CAR-T therapy," said Daniel Hbert, Medical Director, Novartis Pharmaceuticals Canada Inc. "Novartis is committed to bringing additional qualified treatment centers from other parts of the country into the network to give Canadians the opportunity to be treated closer to home."

Due to the sophisticated and individualized nature of Kymriah, treatment sites that are part of the network are required to be FACT-accredited (Foundation for the Accreditation of Cellular Therapy), qualified to perform intravenous infusion of stem cells collected from the bone marrow of a donor, also referred to as allogeneic hematopoietic stem cell transplantation (alloSCT) and have experience with cell therapies, leukemia and lymphoma to facilitate safe and seamless delivery of Kymriah to eligible patients.

"We are thrilled with this news because we will now be able to treat patients at our institution with the knowledge that their therapy will be publicly funded. We see this as a significant step forward. The young patients we see who have refractory or relapsed B-cell ALL are desperately in need of a new treatment option. Kymriah brings hope to patients who are literally in a fight for their life." said Dr. Henrique Bittencourt, hematologist at the CHU Sainte-Justine in Montreal and Associate Professor, Department of Pediatrics, Universit de Montral.

"The expertise at HMR has raised the profile of our organization, which is a major Quebec, Canadian and worldwide pole for health innovation. Thanks to the dedicated work of our care, research and teaching teams, patients can now access this new treatment with demonstrated effectiveness and impact on quality of life," said Sylvain Lemieux, President and CEO, Centre intgr universitaire de sant et de services sociaux (CIUSSS) de l'Est-de-l'le-de-Montral.

About Kymriah Kymriah (tisagenlecleucel), a CD19-directed genetically modified autologous T-cell immunocellular therapy, is approved to treat two life-threatening cancers that have limited treatment options and historically poor outcomes, demonstrating the critical need for new therapies for these patients.

Kymriah is approved by Health Canada for use in pediatric and young adult patients 3 to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) who are refractory, have relapsed after allogenic stem cell transplant (SCT) or are otherwise ineligible for SCT, or have experienced second or later relapse; and for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphomai.

Kymriah is a one-time treatment that uses a patient's own T cells to fight and kill cancer cells. Bringing this innovative therapy to Canadian patients requires collaboration among many health system stakeholders.

Kymriah (tisagenlecleucel) Important Safety InformationThe full prescribing information for Kymriah can be found at: http://www.novartis.ca

Novartis Leadership in Cell and Gene TherapyNovartis is at the forefront of investigational immunocellular therapy and was the first pharmaceutical company to significantly invest in CAR-T research, work with pioneers in CAR-T and initiate global CAR-T trials. Kymriah, the first approved CAR-T cell therapy in Canada, is the cornerstone of this strategy. Active research programs are underway targeting other hematologic malignancies and solid tumors, and include efforts focused on next generation CAR-Ts that involve simplified manufacturing schemes and gene edited cells.

About Novartis in CanadaNovartis Pharmaceuticals Canada Inc., a leader in the healthcare field, is committed to the discovery, development and marketing of innovative products to improve the well-being of all Canadians. In 2018, the company invested $52 million in research and development in Canada. Located in Dorval, Quebec, Novartis Pharmaceuticals Canada Inc. employs approximately 1,000 people in Canada and is an affiliate of Novartis AG, which provides innovative healthcare solutions that address the evolving needs of patients and societies. For further information, please consult http://www.novartis.ca.

About NovartisNovartis is reimagining medicine to improve and extend people's lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world's top companies investing in research and development. Novartis products reach more than 750 million people globally and we are finding innovative ways to expand access to our latest treatments. About 108,000 people of more than 140 nationalities work at Novartis around the world. Find out more at http://www.novartis.com.

Kymriah is a registered trademark.

References_____________________________________________i Novartis Pharmaceuticals Canada Inc., Kymriah Product Monograph. January 7, 2019.ii Quebec Ministry of Health and Social Services press release. October 8, 2019. Available at: https://www.newswire.ca/fr/news-releases/la-therapie-car-t-cell-maintenant-disponible-au-quebec-821953237.html

SOURCE Novartis Pharmaceuticals Canada Inc.

For further information: Novartis Media Relations, Daphne Weatherby, Novartis Corporate Communications, +1 514 633 7873, E-mail: camlph.communications@novartis.com

http://www.novartis.ca

See more here:
Novartis completes certification of initial sites in Quebec for first approved Canadian CAR-T therapy, Kymriah (tisagenlecleucel)(i) - Canada NewsWire

Feeling tapped out. Foggy. Just not all that into sex. Gotta be your testosterone, ads would have you believe. And were believing it, too, with the number of T-supplement users tripling from the early 2000s through 2016.

Dont get us wrong: Testosterone is one critical hormone. Babies first encounter it in utero, when it triggers the differentiation of boys from girls. In puberty, it contributes to your bone growth and muscle mass, and continues to affect functions including your red-blood-cell production and mood stability.

But the message those ads are sending plays right into the economic and social anxieties men are facing. Its like when anti-anxiety meds such as Valium first came onto the scene, says urologist and MH advisor Elizabeth Kavaler, M.D. All these middle-aged women were addicted to Valium, because that was the solution to everything. Testosterone has become the new answer for a life of quiet desperation. More and more of us are feeling the exhaustion of uneasiness. We are being asked to do more with less. Were just trying to get through the day alive. Men think, Well, if I just get a little testosterone, Im going to feel great! Dr. Kavaler says. And thats not the case.

Theres so much information out there about Tmuch of it speculation and lorethat leads us to jump to conclusions about it. Men put all kinds of psychological weight on their testosterone numbera low one makes you think youre somehow less manly; a high one means youre basically LeBron Jamesand thats where we get things wrong. Theres little evidence for those stereotypes. Low doesnt automatically imply youre weak or retiring; high doesnt guarantee you muscles, aggressiveness, or MVP athletic performance.

A low number might not even be a low number for very long. It might just indicate that you havent been treating yourself very well. As long as your T is in the normal range, theres nothing about a high number thats better than a low one, or vice versa.

In the name of science and good journalism, I got my testosterone tested twice while writing this story. It put my assumptions up against a pretty big test, too (more on that later).

What do you really know about this famous hormone? Here, we break down the best and latest information to give you the clearest picture yet of what T means for you. And whether, maybe, you should be taking testosterone after all.

As many as 5 million men in the U.S. (generally older men) do actually have low levels of the hormone. To know if your testosterone is low, first see if you have any symptoms, which include: erectile problems, lack of energy (never feeling rested, no matter what you do; having a paunch; an AWOL libido (not just not wanting to have sex on a Thursday night after a crushing week, but lack of the kind of base-level sex drive wherein you get turned on by the sexy person you spot on the street, explains Tobias Kohler, M.D., of the Mayo Clinic).

With testosterone, as with life, normal is nuanced. And fraught (but shouldnt be). To get an accurate reading, you should have at least two tests, since testosterone is constantly in flux. It peaks in the morning, so if youre young and on a typical sleeping schedule, aim to be tested by 10:00 a.m. If youre over 50, it doesnt matter as much.

Be aware that your level can be affected by certain social factors and health habits. In the new book Testosterone: An Unauthorized Biography, scientists Rebecca M. Jordan-Young and Katrina Karkazis point out that T levels even respond to social factors like feedback. For instance, rugby players who watched video of good game plays and got positive feedback had up to a 50 percent increase in T compared with guys who were shown their mistakes and received critical assessments.

Resistance training can also give you a short-term boost in testosterone. Cardio doesnt elevate T levels as much in normal-weight men, says Jesse Mills, M.D., the director of the Mens Clinic at UCLA. But heres the thing: Jordan-Young and Karkazis dug through the research to find that T levels alone dont deserve the credit when it comes to an athletes performance. And cutting sleep short and taking multivitamins with biotin can push testosterone levels down (skip the vitamins for three days before testing).

So get your tests on days that are typical for you. And when you get your number, dont read too much into it. A T level of 264 to 916 nanograms per deciliter of blood is generally considered normal. If you are close to 264 and you feel fine, then youre no less healthy than a guy whose level is 700 and also feels fine. (Theres an exception to that, though: If your T level is below 300 and you have low-T symptoms, then docs would consider you in a low-T category)

Not reading into it is harder than it sounds. I got my first test at the tail end of a busy week. Id slept less than five hours the night before, then scrambled to the phlebotomist in a daze. My number: 287. Thats in the normal range, but just barely. I have no symptoms of low T, but it was hard to shake the feeling that there was something wrong with me, even though I know that normal is normal, no matter where it is in that range. Eleven days later, I was tested again. My number was 429. Why such a dramatic change? It might be because Id slept better and cut out my multivitamins.

Irrational or not, I felt like more of a man. The whole experience was a microcosm of our relationship with T. We act like its destiny, but its just biologyeasily misunderstood and more varied than we think.

The single best thing you can do to improve your level is be healthier. Avoid stress, get more sleep, and lose weightan enzyme in fat tissue converts testosterone to estrogen. Thats one reason flab can lower your T. Its also why overweight guys can develop man boobs, and why bodybuilders who juice can also develop man boobsthey dont have much fat, but theyve jacked their T levels so high that theres a lot of it available to be turned into estrogen. Thinking of T strictly as the male sex hormone oversimplifies the complex hormonal interactions that make our bodies work. Which is also why, if you can avoid it, you dont want to go with the needle-in-the-butt routine to raise your T.

But that might not work. If your level is low enough to warrant more aggressive treatment, your doctor can prescribe a drug that causes your pituitary to tell your gonads to make more testosterone. The typical choice is clomiphene citrate (Clomid), a common fertility drug for women. Using it doesnt exempt you from needing to get healthy, though, as it doesnt diminish the risk of losing T to bad sleep and a beer belly.

Then theres always testosterone-replacement therapy, which should be your last resort. (When you give your body T, it stops making its own, and theres no guarantee it can start again.) If, though, you and your doctor decide its the way to go, youve got options. You can try a testosterone replacement gel, a topical thats easy to use but can rub off on your partner or kids. There are pills, which are even easier to use than the gel and can deliver higher levels. Theres subcutaneous pellets, or rice-sized inserts that live directly under your skin. And then theres that needle in the butt, which can provide a major boost but is generally only used by docs who specialize in testosterone therapies.

Whatever you choose, be glad that weve moved past the early days of replacement therapies, like one in the 1920s that involved transplanting goat testicles into patients. Believe it or not, it didnt work, and it also didnt make anyone feel like more of a man.

Read the original here:
The Truth About Low Testosterone Levels, According to Experts - menshealth.com

BURLINGTON At the Womens Health and Cancer Conference, one workshop gave a behind-the-scenes look at breast cancer diagnosis, treatment, and care from the perspectives of the different doctors involved on a breast cancer team.

The speakers at the Oct. 4 workshop included a breast surgeon, a radiation oncologist, a medical oncologist, a radiologist, and a pathologist. The team walked through the timeline of a patient with breast cancer, how they diagnosed the cancer, and what their roles as doctors were through treatment.

Diagnosis

Radiologist Erin Tsai spoke about her primary role in diagnosing breast cancer through images. As a radiologist, Tsai interacts frequently with patients to conduct screenings, mammograms, MRIs, and ultrasounds. The patient that the team discussed was diagnosed through screening, meaning that during the patients annual mammograms, the radiologist detected an abnormality. The patients masses were visible via imaging, but Tsai also emphasized how comparing yearly exam results was important in judging its irregularity.

Since she detected a mass, Tsai said the next step was to go immediately to ultrasound which would give a better picture of the inside of the breast. She also noted that ultrasounds are cheaper and more comfortable for the patient. Affirming that the mass was highly suspicious, Tsai said that the next step was to perform a biopsy and send samples of the mass to the pathologist to study and diagnose.

A big key, she said, was how the mass did not appear to respect tissue plains of the breast. This characteristic, among others, implied that the mass was highly suspicious.

Uyen Phyong Vietje, a pathologist, emphasized this point as well. She described her job as intimately familiar with tissues, as her work on the team is to study tissue samples and diagnose the cancer. Vietje noted how, in a magnified image of the sample, the cells stuck together but did not form any architecture. They clearly had no respect for surrounding tissue, she said, indicating that this sort of haphazard array of cellsstructureless with no awareness of surrounding tissuewas evidence of an invasive malignant cancer.

Vietje also noted that the patient was Estrogen receptor (ER) and Progesterone receptor (PR) positive. ER and PR are two types of breast cancer that are fueled by hormones, estrogen and progesterone. Knowing the type of breast cancer can help in shaping what treatment looks like.

What are the different types of breast cancer?

According to the Mayo Clinic, there are four main groups used to categorize breast cancer, including: luminal A, luminal B, HER2 positive, and triple-negative. Luminal A, the first group, includes tumors that are ER and PR positive, but negative for HER2. This means that the tumor is fueled by estrogen and progesterone hormones in the body and can often be treated with chemotherapy and hormone therapy.

Luminal B includes tumors that are ER positive, PR negative, and HER2 positive. HER2 positive means that the cancer cells have an excess of a certain growth factor protein--HER2 for short. Luminal B treatment often includes chemotherapy, hormone therapy, and treatment targeted directly at HER2.

HER2 positive is negative for ER and PR hormones. According to Mayo, this strain of breast cancer is often more aggressive than other types, however prognosis is actually quite good. Treatment often includes chemotherapy and treatment targeted directly at HER2.

Triple-negative breast cancer is negative for ER, PR, and HER2. This type of breast cancer is one of the most difficult to treat, since typical treatments like hormone therapy or drugs that target the first three groups are ineffective. In this case, chemotherapy is frequently used. According to John Hopkins Medicine, triple-negative occurs in 10 to 20 percent of diagnosed breast cancers and is more likely to spread and recur than other forms of breast cancer.

Treatment

As a breast surgeon, Mary Stanley is often the first person to participate in treatment. According to her, surgery is often the first step when tumors are small and there is uncertainty about whether chemotherapy is required. Stanley stated that often, if a tumor is large, the team plans to do chemo first to shrink the tumor and then proceed with surgery.

In the case of this patient, Stanley performed a lumpectomy to remove only the mass. Another surgical option is mastectomy, which removes the whole breast including the mass. According to Stanley, the choice between a lumpectomy and mastectomy are personal to each patient, and the difference in survival is often similar, although lumpectomies can leave the door open for cancer to recur.

Once the lumpectomy was conducted, Stanley sent the tissue to Vietje in pathology again where she measured the tumor size and scored it on a scale. This information helps oncologists in determining post-surgical treatment.

After surgery often comes chemotherapy and radiation.

Medical oncologist Hibba Rehman participates in chemotherapy and hormone treatment. Decades ago, everyone would get chemotherapy because we didnt know how tumors would behave, she said. Now we have a test to determine how tumors will behave. Certain markers tell us whether tumor cells will develop more rapidly.

Patients with ER and PR positive breast cancer are considered low-risk and often receive hormone treatment. Patients with a higher risk type of breast cancer, like HER2 positive or triple negative, often need chemotherapy. According to Rehman, the patient had a high risk of recurrence, not only in the breast, but anywhere else in the body. [There was] a small risk of tumor cells breaking off and going into blood circulation. That is why systemic treatment is so important, why chemo is so important, she said.

As a radiation oncologist, Ruth Heimann also works with patients to advise whether someone is a candidate for radiation. In the case of a lumpectomy, Heimann examines the margins of the cancer and Vietjes measurements of the tumor to decide whether radiation is necessary.

Margins are exceedingly important because they decrease the chance of cancer returning in the breast, she said. Now we know that radiation can take care of the surrounding possible disease in the breast without performing a mastectomy. If the patient is young, Heimann said that radiation often takes about six weeks, followed by chemotherapy. Older patients often have a slightly shorter radiation, about four and a half weeks.

Its like a job, she saidpatients receive radiation daily, five days a week. Without radiation, patients who have lumpectomies have a higher chance of recurrence. According to Heimann, with radiation treatment, there is less than a five percent chance of recurrence.

Ultimately, the patient underwent a lumpectomy, four cycles of chemotherapy, hormonal treatment, and finally radiation.

Continued here:
Breast cancer diagnosis and treatment | News | samessenger.com - St. Albans Messenger

This transcript has been edited for clarity.

Thomas Allison, PhD: Greetings! I'm Tom Allison, cardiovascular specialist at Mayo Clinic. During today's roundtable, we'll be discussing lipoprotein(a). I'm joined by my colleague, Dr Steve Kopecky, who specializes in this area. Steve, what is lipoprotein(a) and why do we have it? What role does it play?

Stephen L. Kopecky, MD: Lipoprotein(a) is a combination of a couple of standard molecules that we all know about. One is an LDL cholesterol-type molecule or low-density lipoprotein. The second is an apolipoprotein(a) which is bound to the LDL-like molecule at the ApoB receptor with a disulfide bond. Now, what does that mean? Lp(a) is a cholesterol-type molecule, basically.

Allison: I understand that there are different sizes of these Lp(a)s.

Kopecky: Yes, there are different sizes because the apolipoprotein portion can have different kringles. Some are very big, some are very small. The smaller ones seem to be more atherogenic or cause more problems.

Allison: Like the small dense LDL.

Kopecky: Like the small dense LDL. One question that comes up is, why do we even have this molecule? It seems to promote clotting, which may not be a good thing, although years ago if you had trauma, it may have helped with wound healing or clotting. It may have helped prevent excessive bleeding in childbirth, so there may be a reason why we have it in our bloodstream.

Allison: What evidence do we have that this causes heart disease or contributes to our risk for heart disease? And I presume that we're talking about coronary artery disease, right?

Kopecky: Ischemic stroke also could be involved.

First, what is it about this molecule that may be causing problems? The LDL particle can actually promote atherosclerosis. We also know that the apolipoprotein particle is similar to plasminogen, so it can promote clotting. It inhibits fibrinolysis. And the third factor is that it is an inflammatory molecule.

So it does three things: causes atherosclerosis, causes the plaque rupture with inflammation, and then causes clotting at the site of plaque rupture. Large observational studies, such as the INTERHEART study, which involved many nations, show that individuals with elevated lipoprotein(a) have an increased risk for myocardial infarction (MI).[1]Mendelian randomization studies in large numbers of patients/subjects suggest that if you have an elevated lipoprotein(a), you also have an increased risk for MI and stroke.[2]

Allison: Am I correct that some recent trials have shown that the on-treatment level of Lp(a) in a clinical trial actually correlates with the event risk?

Kopecky: Yes. If you look at LDL cholesterol trials where they gave statins to control LDL, the best predictor at that point of recurrent events was actually the lipoprotein(a) level, not the LDL level.[3,4]

Allison: What is the cut point? At what level do we see the increased risk? I know there's some controversy about what the cut point is.

Kopecky: Yes, because a lot of it's observational, and [approximately] 80% of individuals globally have normal levels of less than 50 mg/dL. In the US, we have an average of about 20 mg/dL. If you look at certain ethnic groups, Asians and Caucasians are very similar; African Americans and Arabs also have higher levels, maybe two or three times higher. The question is, how much of that goes into risk? And that's not quite clear. Is an African American's risk higher because they have a higher Lp(a)? That has not been worked out.

Allison: So 50 mg/dLis that the number?

Kopecky: In general, the average number is 20 mg/dL. Over 50 mg/dL, we start to call it increased risk; that's what most guidelines have said. If you're using nmol/L, 100 or 125 is elevated risk.

Allison: In the prevention clinic at Mayo, do you measure Lp(a) on everybody, or are there specific groups for whom you think it's more important?

Kopecky: People have said that we should measure it in everybody. I don't think we're quite there, mainly because we don't have a treatment yet. But also because the people who may benefit the most are the ones who come in with early atherosclerosis or they have a family history, and they say, "My older brother just had a heart attack at age 48." That may be a good time to check it.

Patients who have recurrent atherosclerotic events in spite of optimal treatmenta case has been made to check those patients. And then there are patients who have FH, familial hypercholesterolemia. About 1 in 5 people (or 1 in 3) with FH have elevated lipoprotein(a). It increases risk, so we check.

The last group is aortic stenosis; bicuspid aortic valve is probably the prototype of that. There's evidence that individuals with elevated lipoprotein(a) and bicuspid aortic valve have more rapid progression of aortic stenosis.

Allison: That's new, right?

Kopecky: That's fairly new. We're starting to think of that when we look at patients with the bicuspid aortic valve.

Allison: So now you have lipoprotein(a) and it's over 50. What do you do?

Kopecky: First off, you make sure that when we're talking about over 50, we're talking about over 50 mg/dL versus like 125 nmol/L. The reason why that's important to differentiate is because the mg/dL is the mass concentration whereas nmol/L is the particle concentration. And as you implied, the particles are different sizes, so we can't convert one to the other like we can with LDL or HDL. It has to be a completely different measurement. There's a push right now to have a single way of measuringthe nmol/L, which would take into account the particle size.

Allison: And that's 125 nmol/L.

Kopecky: It would be like 125 nmol/L. So if it's high, what do we do? Well, lifestyle is always very important, although 80%-90% of your Lp(a) level is genetically determined. It's a codominant inheritance, meaning you can get a gene from each parent, and both will raise it more.

You can give things like niacin or hormone replacement therapy. We know that can lower it, but it doesn't lower events; in fact, it may increase cardiovascular events, so it's not recommended. Statins don't affect it. The PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors lower it by maybe 25%, but they're not indicated for high lipoprotein(a).

Lipoprotein apheresis can be helpful in a very small percentage of patients. So we have some treatments, the PCSK9 inhibitor, but it's not yet indicated for lowering it.

Allison: Am I correct that there is a new drug under development that was presented at the American Heart Association scientific sessions, that has shown a significant (ie, 80%) lowering effect, but it's not available? Is that right?

Kopecky: Right. It's an antisense oligonucleotide that actually lowers Lp(a) significantly. It's undergoing clinical studies and we don't know the outcomes yet. It sounds like it's a good idea, but we would need the outcome studies to show that it benefits patients.

Allison: No dietary therapies?

Kopecky: Lifestyle is important, but it doesn't lower your lipoprotein(a). It lowers your risk, but that's separate from the Lp(a).

Allison: Steve, any other points we should make about this?

Kopecky: It's always good to look at the guidelines. The recent ACC/AHA lipid guidelines say you should consider lipoprotein(a) over 50 mg/dL or 125 nmol/L as a risk enhancer ,so be a little more aggressive in treating those patients.[5]

It may be the risk enhancer you use with some patients in primary or secondary prevention, and it's something worth checking, especially if you have patients who have recurrent events or early events, or a family history of early events, because it helps you be more aggressive in treating the patients.

Allison: Do you ever bring in a patient's family members and check them? If, for example, you're 40 years old and you have an MI, should your brother and your kids get checked?

Kopecky: The cascade screening. Yes, we actually have a letter that we give patients. Once we check them and it's elevated, we say, "Give this letter to your first-degree relatives. You don't have to talk to them; the letter explains everything." It says the patient had this elevated lipoprotein(a), which can be associated with increased risk for heart disease, and the relative should take this letter to their primary care provider to check [lipoprotein(a)].

Allison: Steve, thanks for this update and for your insights. I want to thank everyone for joining us on the heart.org | Medscape Cardiology.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube

More here:
The Lowdown on Lipoprotein(a) - Medscape

THE PILL may be the most popular method of contraception in Dorset but more women in the county are turning to longer-lasting contraceptive methods such as the coil, implants and injections, figures reveal.

NHS Digital data shows 3,605 women with a preferred main method of contraception attended a sexual health clinic in Dorset to obtain the method they required in 2018-19.

Of these, 57 per cent chose long-acting reversible contraception, up from 53 per cent the year before.

However, nearly 35 per cent of all women using contraception in Dorset chose the pill, figures reveal, although this was down from 38 per cent one year ago. NHS guidelines say the pill is more than 99 per cent effective at preventing pregnancy if it's taken according to instructions.

But with sexually transmitted-infection rates rising, the British Association for Sexual Health and HIV says people should consider if their contraceptive choices were protecting them from STIs.

And the contraceptive method with the highest rate of success in this direction, condoms, are only being used by seven per cent of women, although this is up one percentage point from six a year ago.

The new stats also reveal that when it comes to contraception, more women are looking at the most modern methods.

Those wanting a more permanent method can get a copper-emitting intrauterine device more commonly known as the coil which can last for up to 10 years, or a hormone-based intrauterine system, for up to five years.

The implant, which is put into the upper arm, lasts three years and is easier to remove than the coil. A contraceptive injection covers a shorter period, lasting eight to 13 weeks.

In Dorset, 22 per cent of women said they were using the coil or intrauterine system as their main method of contraception, while 27 per cent opted for the implant and eight per cent for the injection.

Across England, fewer people are getting contraception from their local sexual health clinic, dropping from 1.87 million in 2014-15 to 1.40 million in 2018-19.

President of the Faculty of Sexual and Reproductive Healthcare, Dr Asha Kasliwal, said the 25 per cent drop shows that women and girls appear to be finding it harder and harder to access essential contraceptive services.

This is evidenced in worsening indicators in womens reproductive health almost half of pregnancies in Britain are unplanned or ambivalent," she said. "Abortion rates for women over 30 have been steadily increasing for the last 10 years.

Across England, 311,000 women requested the pill at sexual and reproductive health services last year, down from 427,000 in 2014-15.

A total of 352,000 women now use long-acting reversible methods, up from 346,000 four years ago.

A spokesman for the Department of Health and Social Care said: We have a strong track record on sexual health with teenage pregnancies at an all-time low. Contraception is the best way to avoid unintended pregnancy and we are pleased to see uptake of long-acting reversible contraceptives has increased.

Prevention is at the heart of the NHS Long Term Plan, and comes alongside the 3 billion we are giving to councils to fund

Go here to see the original:
Women still prefer the pill to any other contraceptive - Bournemouth Echo

Boys with fragile X syndrome (FXS) who experience negative emotions such as anger and fear up to preschool age are more prone to develop anxiety, a new study suggests.

The study, Early negative affect in males and females with fragile X syndrome: implications for anxiety and autism, was published in the Journal of Neurodevelopmental Disorders and was conducted by University of South Carolina researchers.

FXS is the most common genetic cause of autism and intellectual disability. The prevalence ofautism spectrum disorder (ASD), an umbrella term for autistic behaviors, ranges from 5075% in males and reaches 25% of females with fragile X. Anxiety also is common, and is present in 86% of males and 77% of females with fragile X.

Early predictors of anxiety and ASD in fragile X are lacking. Also unknown is whether the prevalence of these comorbidities is different between males and females with fragile X.

Negative affect is a concept that includes fear, sadness, frustration, and difficulty regulating emotions, involving a generally negative way of experiencing the world. It is used in clinics as a predictor of anxiety and ASD for infants and toddlers.

Seeking to assess the prevalence of negative affect and whether its impact is different in boys and girls with fragile X, researchers followed a total of 185 children from the age of 6 months to 60 months (5 years), of whom 116 have fragile X (75% male) and 69 with typical development (79.7% male).

The study also intended to explore whether negative affect could predict anxiety and ASD in children with fragile X.

Negative affect was measured using the Rothbart Temperament Questionnaires, one of the most-used measures for this purpose in infancy and childhood. The questionnaires are answered by parents and include three different sets according to the childs age: the Infant Behavior Questionnaire-Revised for infants between 6 and 18 months; the Early Childhood Behavior Questionnaire for children between 1836 months; and the Childrens Behavior Questionnaire for children 3660 months.

The Spence Childrens Anxiety Scale for Parents (SCAS-P) was used to measure anxiety, and the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) was used to explore ASD. The SCAS-P score has an average of 50, and higher scores represent more anxiety symptoms. The ADOS-2 scoring system ranges from 1 to 10, and higher values reflect more severe ASD symptoms.

The Mullen Scales of Early Learning (MSEL) was used to measure development level, and spans motor and visual domains, as well as language skills.

The analysis revealed that negative affect increased from infancy through preschool in both controls and children with fragile X. However, the increases were steeper in children with fragile X, with lower levels than in the controls from 6 to 36 months of age, followed by increases to similar levels of controls from 36 months onward.

This atypical variation in fragile X, the scientists observed, was largely driven by sex, specifically males. After showing lower levels than girls during infancy, boys with fragile X showed steep increases across the toddler and preschool years. In contrast, girls showed a flatter trajectory throughout the study.

Male infants with FXS displayed lower negative affect than female infants with FXS at 6 months, equivalent levels at 12 months, and higher negative affect by 36 months, the investigators wrote.

The smaller increase in girls compared to boys may reflect their milder symptoms, the scientists said.

Of note, no gender differences were seen in the control group.

Increased negative affect predicted anxiety symptoms in boys, but not in girls. In turn, negative affect was not linked with ASD in fragile X, irrespective of gender.

Overall, these results suggest that temperamental negative affect can be an important early marker for anxiety in young children with FXS, the researchers wrote. Also, they provide opportunities for the pursuit of an important target for early detection and intervention.

These findings also show that including both males and females in FXS research can enhance our understanding of the unique vulnerabilities and needs of either sex, they added.

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.

Total Posts: 7

Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.

Read this article:
Study: Negative Emotions Increase Risk for Anxiety in Boys with - Fragile X News Today

Mathew Knowles, the father and former manager of singers Beyonc and Solange Knowles, revealed last week that he has been diagnosed with breast cancer.

>> Read more trending news

Knowles, a music executive, made the announcement during an interview onABCs Good Morning America.

Around 2,670 men are diagnosed with breast cancer each year and 500 of them die from the disease,according to the Centers for Disease Control and Prevention.

Knowles, 67, pointed out in the GMA interview that the key to a positive outcome with male breast cancer is, like other cancers, early detection and treatment.

He said he first realized something was wrong in July when he noticed a dot of blood on his shirt. He said he could not find out where the blood came from, but after a few days, he decided to check his breast and discovered some discharge from his nipple.

So, I squeezed my nipple and sure enough, a little discharge came out, bloody discharge,Knowles told The New York Times. I immediately called my doctor.

Knowles had a test done on the discharge, then a mammogram which revealed he had stage 1A breast cancer. He had a mastectomy just weeks after. During the mastectomy, Knowles also had three lymph nodes removed from under his arm to determine if the cancer had spread from the breast. It had not, Knowles was told.

Women are 10 times more likely to develop breast cancer than are men, but the rareness of the disease in men is a problem in early detection and treatment,according to the American Cancer Society.

Finding breast cancer early improves the chances that male breast cancer can be treated successfully. However, because breast cancer is so uncommon in men, there is unlikely to be any benefit in screening men in the general population for breast cancer with mammograms or other tests,the ACS said.

Here is a look at the signs and symptoms of male breast cancer, treatment options and who is more likely to get the disease.

How common is male breast cancer?

It is uncommon for men to develop breast cancer. Male breast cancer accounts for less than 1 percent of all cancer diagnoses. On average, 1 man in 833 will develop breast cancer over a lifetime.

What are the symptoms?

The symptoms of male breast cancer are similar to the symptoms of female breast cancer. They include:

What risk factors increase a mans chance of developing breast cancer?

The risk factors that increase a mans chance of developing breast cancer are:

Who is likely to get breast cancer?

While men can be diagnosed with breast cancer at any age, breast cancer is very rare in men under the age of 35. Most breast cancers in men are found when they are between the ages of 60 and 70. A lump in the breast area at any age needs to be evaluated by a physician.

Black men are more likely to be diagnosed with breast cancer than are white men.

What happens when breast cancer is suspected?

Your doctor will ask you some questions about your medical and family history if you come to him or her with breast cancer symptoms. After that discussion and a breast examination, a combination of medical tests will likely be ordered.

Those tests include:

What is the treatment?

Treatment for breast cancer depends on the stage of the cancer or if the cancer has spread beyond the breast. Among treatment options are:

What is the prognosis?

The outcome of cancer treatment depends on many factors. If the cancer is detected early before it has had a chance to spread, the five-year survival rate is 100%. Almost half of all male breast cancers are diagnosed at this stage, according tocancer.net.

The five-year survival rate for men with stage II disease is 87%, for stage III disease is 75% and for stage IV disease, when the cancer is advanced and has spread to other parts of the body, 25%.

Support real journalism. Support local journalism. Subscribe to The Atlanta Journal-Constitution today. See offers.

Your subscription to the Atlanta Journal-Constitution funds in-depth reporting and investigations that keep you informed. Thank you for supporting real journalism.

The rest is here:
Mathew Knowles breast cancer: What are the symptoms, treatment for male breast cancer - Atlanta Journal Constitution

Cambridge, Massachusetts-based bluebird bio and Bagsvaerd, Denmark-based Novo Nordisk announced they have agreed to collaborate to develop next-generation genome editing therapies for genetic diseases, including hemophilia. The deal will last three years, with a top priority to develop a gene therapy for hemophilia A.

The partnership will leverage bluebirds mRNA-based megaTAL technology that is used to silence, editor or insert genetic components. Novo Nordisk has a hemophilia portfolio. The initial focus will be on correcting FVIII-clotting factor deficiency. No financial details were disclosed.

MegaTALs are a single-chain fusion enzyme. It combines the natural DNA cleaving processes of Homing Endonucleases (HEs) with the activity of transcription activator-like (TAL) effectors at the DNA binding region. These proteins are easily engineered to recognize specific DNA sequences.

We are pleased to announce our collaboration with bluebird whose demonstrated capabilities in gene therapy will enable the next-generation of innovative products to make a significant impact on patients lives, said Marcus Schindler, Novo Nordisks senior vice president for Global Drug Discovery.

He went on to say, This important research collaboration aimed at addressing genetic diseases at the DNA level reflects Novo Nordisks enduring commitment and dedication to inventing disease-modifying medicines that can truly change the lives of people living with hemophilia and other genetic diseases.

Novo Nordisk is better known for its strong presence in the diabetes market and for metabolic diseases. However, the company has been increasing its efforts in hemophilia, with its hemophilia A drug Esperoct receiving approval from both the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) this year.

Hemophilia A is found in about one in 5,000 people and hemophilia B in about one in 25,000 male births. It is estimated that more than 400,000 males have hemophilia A or B, which is severely underdiagnosed in developing countries. About 304,000 people are diagnosed with hemophilia A, the result of decreased or defective production of the blood clotting factor VIII. Hemophilia B is not as common, but affects about 136,000 people who have deficiencies in clotting factor IX.

Hemophilia patients often have bleeding into the joints, particularly knees and ankles, and can have uncontrolled bleeding from trauma, surgery, tooth extractions or other minor surgical treatments.

Bluebird bio is a pioneer of gene therapy. On June 3, the European Commission (EC) granted the company conditional marketing approval for its LentiGlobin gene therapy for transfusion-dependent beta-thalassemia (TDT) under the brand name Zynteglo. It was approved for patients 12 years or older with transfusion-dependent beta-thalassemia who did not have a 0/0 genotype and for patients where hematopoietic stem cell (HSC) transplantation wasnt appropriate, but a human leukocyte antigen (HLA)-matched related HSC donor isnt available.

The therapy came with a $1.8 million price tag in Europe, although it has offered a variety of pricing schemes, including a five-year payment plan with annual payments contingent on the therapys continued effectiveness, to offset criticism of the price.

Of the deal with Novo Nordisk, Philip Gregory, bluebirds chief scientific officer, stated, bluebird has made tremendous progress on enabling an in vivo gene editing platform based on our megaTAL technology, including important advances in high-quality mRNA production and purification. We believe this technology has the potential to create a highly differentiated approach to the treatment of many severe genetic diseases. Moreover, we are thrilled to be able to combine this new platform technology with Novo Nordisks deep expertise in hemophilia research and therapeutics. We believe this collaboration will move us toward our shared goal of recoding the treatment paradigm and substantially reduce the burden of disease for patients with factor VIII deficiency.

Original post:
Novo Nordisk and bluebird bio Enter 3-Year Gene Therapy Collaboration Pact - BioSpace

On Monday, October 28, Calcalist, Israeli food processing company Tnuva, and accounting firm KPMG will announce the winner of their annual food innovation competition for Israeli startups. Dozens of Israeli foodtech companies participated in the competition, and the 11 finalists will present their technology at Calcalits Food Tech 2019 conference, which will be held at Tel Aviv coworking space Labs.

DayTwo

Funding: $48 million

Investors: aMoon, Ofek Ventures, Johnson & Johnson, Seventure Partners, Israeli basketball player Omri Casspi

Funding: $100,000

Yoran Imaging

Funding: $1.5 million

Investors: private investors

Funding: $10.25 million

Investors: Fortissimo, Hazera 1939, Dan Danzinger, Roquette

Soos Technology

Founder: Yael Alter

Funding: $1.8 million

Investors: Takwin, Mikal, SIBF, Alon Gozlan

Verstill

Funding: $550,000

Investors: Alex Haruni, Termaips Technologies, F&F

Zero Egg

Funding: $1.05 million

Investors: The Kitchen, New Crop Capital

Zero Egg Ltd. develops and manufactures a plant-based liquid egg that tastes, looks, and functions like a real egg, the company says, and can be used as an egg substitute in any recipe, including to make omelets and mayonnaise. The companys egg substitute has no cholesterol.

TIPA Compostable Packaging

Funding: $49 million

Investors: Greensoil, Chestnut holdings, Horizons Ventures, Blue Horizon Ventures, Triodos Organic Growth Fund

AgrIOT

Funding: $1 million

Investors: private investors

Link:
Meet the 11 Finalists of Calcalist's Foodtech Innovation Competition - CTech

UCLA faculty from the humanities, arts and life sciences answered the question, What is knowledge? Tuesday at the second lecture of a 10-week series.

Tyler Burge, a professor in the Department of Philosophy, said he thinks knowledge exists in many forms including common sense, scientific knowledge and historical knowledge, and should not be considered as a single, unified concept.

I think its very important to be a pluralist about knowledge, Burge said, Im much more fascinated with differences in types of knowledge.

Burge was one of three panelists at the lecture, which was hosted by Victoria Marks, associate dean of academic affairs at the UCLA School of the Arts and Architecture.

This years 10 Questions series is one of the UCLA Centennial Campaigns events. It was sponsored by the Centennial Committee, the School of the Arts and Architecture and a grant from UCLAs Interdisciplinary and Cross Campus Affairs, Marks said in an email statement.

Burge said he thinks moral knowledge is often underrated as a form of knowledge. While morality can be considered subjective in some senses, there are certainly some indisputable moral truths like the unethical nature of torture and slavery, he added.

Shane Campbell-Staton, an assistant professor in the Department of Ecology & Evolutionary Biology, said knowledge is always an incremental building on an existing foundation rather than a genuine unique discovery, and illustrated this through his research with elephants.

Campbell-Staton found that a lack of tusks in elephants is an X chromosome-linked trait that causes death in males before birth, leading to the prediction that two out of three offspring born to tuskless female elephants are female offspring, which served as an incremental increase in knowledge about genetic inheritance.

Campbell-Staton added the Schrdingers cat thought experiment can help reveal the relationship between quantitative and abstract knowledge, as the abstract concept allows us to understand quantitative data. Schrdingers cat is a hypothetical experiment in which one would not know whether a cat placed in a box with poison released at a random point in time was dead or alive.

Sylvan Oswald, an assistant professor in the Department of Theater, read an excerpt of his piece about an insomniac searching for his estranged brother to illustrate the way that art does not fundamentally seek to produce knowledge, but can often generate knowledge as a byproduct.

Oswald added he wrote a play during college and felt a strong impulse that the male character be portrayed by a female actor. Oswald did not know at the time why he was so insistent on the detail, but later realized it was a manifestation of his own suppressed transgender identity.

Its a great example of how the subconscious can know more than the conscious, Oswald said.

Campbell-Staton added it is remarkable how much the unconscious can understand, referring to the way humans react to a roar in the woods.

There are aspects of our basal consciousness that are much older and much wiser (than other parts of our brain), Campbell-Staton said. If you heard a roar, youd probably be scared. You dont know why but youre doing it.

Aya McGlothlin, a recent UCLA graduate who attended the talk, said she liked the seminar-style structure of the event and how the panelists discussed the many different definitions of knowledge.

(The definitions) act as operant definitions, but they are all truth, McGlothlin said.

Paul McGlothlin, a UCLA alumnus who attended the talk, said he thinks the event changed his perspective on the concept of knowledge.

I think whenever anybody poses a really good question, it causes you to think differently, Paul McGlothlin said.

The next lecture in the series, What is justice? will take place Tuesday in Kaufman Hall.

Original post:
'10 Questions' series looks at moral truth and the creation of knowledge - Daily Bruin

I tell everybody I havent heard anything, Green says. I dont fantasize about anything like that. Im just trying to get healthy and go from there.

He also knows its a business: Im prepared for anything. A trades not going to change who I am. Im still going to play. Im still going to be A.J.

Greens in the last year of his deal and the Bengals have never hid from their desire to lock up one of their franchise greats one more time for a third contract that solidifies him as the Bengals all-time leading receiver and locker-room anchor for new head coach Zac Taylors culture.

The injury, coming on the heels of big toe surgery that wiped out the last half of last season, put the contract talks that were percolating during the summer on hold. Now the Bengals are focused on getting a win and Green is focused on getting back healthy. Everybody has to see where everybody is. What we do know is that a fire sale just isnt Bengals president Mike Browns style. A deal with one of his all-time greats is more like it.

It certainly is to Green. As he told Paul Dehner, Jr., of The Athletic last week, he wants to pull The Larry and stay in the same city for his entire career like Fitzgerald has spent his 17 season in Phoenix.

The trade rumors and the start have done nothing to shake him. He says if the contract is fair, hes all in. Whether they re-build or not. He says hes not looking to jump to a hot team.

Thats just not who I am. Im loyal to the person who gave me my shot, Green says. They took care of Larry. Hes a Cardinal. No matter how many times they rebuild, hes a Cardinal. Hes the only guy still there.

So amid the buzz, the contraption strapped to his foot on the training table, the contract, Green is as impassive and as intense as ever. Well see, he says of the future. Right now he just wants to get back and win games and get back in the AFC North race.

I want the team records. I want more Pro Bowls. I want all that, Green says, so when I leave there is going to be a standard. I still want the yardage, I still want thetouchdowns.

He says he also wants to do it for one team. Thats my legacy, he says. Green, 1,877 yards shy of passing Chad Johnson as the Bengals all-time leader, has had to scale back his career projections.

Before the last two injuries robbed him of at least 14 healthy games, he was thinking between 15-16,000 yards. With 8,907 yards, now hes thinking 13-14,000. He thinks that still gets him into the Hall of Fame. He plans on tacking on to those seven Pro Bowls and if he adds two or three he probably will get to Canton. Five more Pro Bowls would make him a no-brainer.

Its 5:30 p.m. More guys are leaving. The thing on his ankle is strapped to a machine humming with stimulation. It alternates between heat and cold, just like Greens frosty brew of passion. A pro's hour remaining.

Its nothing frustrating. Its just time. I just have to be patient, Green says. I cant rush it and not be the same guy and mess around and get hurt again. Ive got to make sure its right before I even step out there.

Go here to read the rest:
AJ Green Feeling A Return: I Think I'll Be The Same Guy - Bengals.com

Something like pineapple, I say. Lychee. Loads of tropical fruit.

Lutz nods, his fingers stained chartreuse with lupulin, a bright green fleck of hop cone stuck to his neatly trimmed mustache. He inhales again.

Maracuja, he says. He nods and smiles. And apricot. Thats Callista.

As in wine, Old World hops are known for their relative restraint and subtlety, versus the bombast of New World varietals. Think of the four, acclaimed noble hopsSaaz, Tettnanger, Spalt, and Hallertauer Mittelfrhthat have made Continental Lagers famous for centuries. But across Europe, hop breeders like Lutz are working to develop an array of exciting new cultivars that stray far from the refined, elegant aromas of tradition. In the place of gentle, cedary notes, these hops might throw off tons of maracuja (also known as passion fruit). Instead of orange blossoms, some of these new hops offer an entire forest of pine trees. Where you might expect delicate spice, you instead get a wacky fruit salad, filled with peaches, melons, and grapes.

While such unusual aromas are probably the most interesting aspects of new hop varieties for beer lovers, breeding programs like those of the Hop Research Center have goals far beyond mere aromaswhich makes a lot of sense when you remember that this institute was founded in 1926, long before the age of tropical-fruit IPAs.

On our walk through the Hop Research Centers greenhouses, laboratories and nurseries, the programs research director, Dr. Elisabeth Seigner, outlines its origins.

In those days it was founded because the growers had great problems with downy mildew. All across Europe, downy mildew was a real problem with all the landrace hops, she explains. While treatments with copper hydroxide helped with the disease, the institute started crossbreeding the traditional hops of the region with wild varieties, which have a natural tolerance for downy mildew. Chemical protection was very effective, but even in those days, we started breeding research, she says.

Today, the breeding program for new cultivars is just one of the institutes five main areas of focus, which also include plant protection, organic hop production, hop analysis, and a hop production advisory service. (Put another way: the institute creates new hops, tests hop pesticides, figures out how to grow hops without any pesticides at all, studies the chemical components of hops, and consults with farmers on their hop farms, working right in the middle of Germanys largest hop-growing region.) Since its humble origins in the fight against mildew on traditional noble hops, the breeding program at Hll has grown into one of the largest in the world.

We are the institute with the highest number of crosses per year100 crosses per year, Seigner says. The next year 100,000 seedlings are raised in the greenhouse, and then they are raised in our kindergarten.

Read more:
To See Into the Future Inside the Old World's New Hop Breeding Programs - Michael Kiser

Deep beneath the oceans surface, warty pink octopuses creep along the seafloor. These members of the octopus species take variations in skin texture to a whole new level. Some have outrageous warts, while others appear nearly smooth-skinned. Scientists werent sure if these octopuses were even members of the same species, and they didnt know how to explain the differences in the animals looks. But in a new study, scientists cracked the case: the deeper in the ocean the octopuses live, the bumpier their skin and the smaller their bodies. DNA revealed even though the octopuses looked different, they were the same species.

If I had only two of these animals that looked very different, I would say, Well, theyre different species, for sure. But variation inside animal species can sometimes fool you, says Janet Voight, associate curator of zoology at the Field Museum, USA, and the lead author of the paper in the Bulletin of Marine Science. Thats why we need to look at multiple specimens of species to see, does that first reaction based on two specimens make sense?

To figure out if the smooth and warty octopuses were the same species, the scientists examined 50 specimens that were classified asGraneledone pacifica the Pacific warty octopus. Plunging deep into the ocean in ALVIN, a human-occupied submersible vehicle, Voight collected some of the octopuses from the Northeast Pacific Ocean. The team also studied specimens loaned from the University of Miami Marine Laboratory and the California Academy of Sciences. They looked at specimens from up and down the Pacific, from as far north as Washington State to as far south as Monterey, California, and from depths ranging from 3,660 feet to more than 9,000 feet below the oceans surface.

The researchers counted the number of warts in a line across each octopuss back and its head and the number of suckers on their arms. They found that the octopuses from deeper in the ocean looked different from their shallower counterparts. The deep-sea specimens were smaller, with fewer arm suckers, and, most noticeably, bumpier skin than those from shallower depths. The thing is, there werent two distinct groups; the animals appearances changed according to how deep they live. Comparing the octopuses DNA sequences revealed only minor differences, supporting the idea that they were all the same species, despite looking so different.

Sometimes when animals look different from each other, scientists can be tempted to jump the gun and declare them separate species especially in the deep sea, where very little is known about animal life and scientists often dont have many specimens to compare. But looking different doesnt necessarily mean that animals are members of different species; take chihuahuas and Great Danes, which are both the same species of Canis lupus familiaris.Dogs different appearances are due to selective breeding by humans, but in the case of the warty octopuses in this study, their different appearances seem to result from environmental influences, because their appearance changes depending on where the octopuses are from.

Scientists arent sure why the variations in skin texture occur with depth. But they do have a hunch about the size difference.

Voight thinks that these octopuses usually eat creatures from the sediment on the ocean floor, passing food from sucker to sucker and then crushing their prey like popcorn. Theres less food as you get deeper in the ocean. So these animals have to work harder to find food to eat. And that means at the end of their lives, theyll be smaller than animals who have more food. If youre a female whos going to lay eggs at the end of your life, maybe your eggs will be smaller says Voight. Smaller eggs mean smaller hatchlings.

Support for this hypothesis comes from the number of suckers on the males arm that transfers sperm packets to females. Earlier research by Voight found that male hatchlings have a full-formed arm with all its suckers in place. The researchers documented that the number of suckers on this arm was way smaller in males from greater depth, and Voight hypothesises it relates to egg size.

The octopus hatchlings in shallower water, only 3,660 feet, are bigger. Their eggs had more yolk. As the embryos grew, they developed farther inside the egg than the ones from 9,000 feet, who were developing in smaller eggs. They had less energy to fuel their growth before they left the egg, so they made fewer suckers, says Voight. Seeing these physical manifestations of octopuses food limitation provides a hint of how they might fare as climate change progresses and the octopuses food supply fluctuates.

Voight notes that this study, which shows that different-looking octopuses can still be the same genetic species, could help researchers down the line trying to identify life forms in the deep sea. Remotely operated vehicles collect video footage of the ocean floor, and it can be used to estimate the number of species present if we know what they look like. Thats why, Voight says, its so important to examine specimens in person and use characteristics you cant see on video to identify species boundaries.

Theres still just so much we dont know about the deep sea. We need to be able to understand the information thats becoming available from ROV footage. And we can only do it by knowing what the animals look like.

Visit link:
The deeper the octopus the wartier the skin - SciTech Europa

Mike Babcock addressed the media after practice on Wednesday, discussing the challenge ahead against Tampa Bay, William Nylanders impressive start to the season, Patrick Marleau signing in San Jose, the teams third line, and more.

How good of a hockey league is this that you go from St. Louis one night to what you are going to see tomorrow night and how you guys match up against this challenge?

Babcock: Itll be good. I really liked our St. Louis game. I thought we played well. I thought we did a ton of good things. Youve got to win in the end. Bottom line is thats what the good teams do they just hang around and hang around and find a way to win. We didnt, so weve got to take a lesson from that, but there were lots of good things in that game. Ive liked three of our four games. I didnt like our Montreal game. Now weve got to get ready for a good Tampa team. It should be a lot of fun. We usually have good games against Tampa.

Its early in the season, but do you see a hungrier player in William so far?

Babcock: Were talking about hunger? Like, he wasnt here. It was hard to be hungry. Hows that? When you get here and the league is going 900 and youre going 20, shes tough. I just think that Willy last game won a bunch of races and a bunch of battles. When he wins races and wins battles, he has the puck. Sometimes you have the puck because other guys get it to you, but if you want to have the puck all the time, you can count on your teammates a bit, but youve got to count on yourself. The more he goes to get it with his speed, his tenacity, his stick lifts and with his contact in those traffic areas, the more he is going to have the puck and the more dynamic hell be.

Are you going to keep Spezza and Petan in the lineup here?

Babcock: Whatever we did last game, thats what were doing this game.

What did you see that you are breaking the rotation?

Babcock: Theyve had two apiece. We gave everybody a real One of the reasons we play eight exhibition games the NHL guys are playing four is that it gives us a real fair chance to evaluate everyone else. Any way you look at it, guys have had quite a bit. Not only do we want to be right, we want to give the guys a fair chance. We think weve done that. That doesnt mean itll be the same next game, but that is what were doing.

What was your reaction to the San Jose Sharks bringing back Patrick Marleau?

Babcock: Yeah, it was good. I texted him back and forth last night. Firstly, its what he wanted and it was what was best for his family. Thats what he wanted when the season was ended. Im glad it has all worked out for him. It probably took longer than he wanted, but he said his wife and kids were really happy. As we all know anybody who has a wife and kids thats a real important thing. Patty wants to keep playing past this year as well, so we wish him luck.

When he went unsigned in the summer, did you guys maybe want to try to bring him back?

Babcock: We were in no position if you remember what was going on through the summer to sign anybody. We never got into any of that. Obviously, he didnt want to play here. He wanted to play in San Jose, where his family is going back to. That took us out of that mix.

When you look back at his time here, what is kind of the big overarching takeaway from it?

Babcock: Well, John Tavares came here. Everyone can speculate on why guys come, but when youve got people to come from other organizations like Patty did, that starts it. And then you move on from there. To me, that was a big part of it.

I thought he really helped out our young guys. He gave us a real good pro an example of how to eat, how to workout, how to train, how to practice so we could get on the process of changing the culture.

As time goes on and you get more and more guys, and your own guys grow up, it is probably not as important, but it sure was off the start. When Tavares is looking for someone to phone to find out whether he should come here or not, and youve got Patrick Marleau to phone, its a pretty good guy to phone.

Is it passion that makes players so effective at the age of 40, going into a third decade at thispoint?

Babcock: Well, theyre genetic freaks, too. Lets not kid ourselves. You look around the world and the average 40-year-old isnt playing in the NHL. In saying that, youve got to love the game and your family has got to be committed to you loving the game. When youre a pro athlete, it is a lot about you. Theyve got to make that commitment with you. Obviously, theyve all decided this is a good thing for Patty. He is a good player.

The lineup against Tampa isnt necessarily the lineup goingforward, but are you looking forward to Rasmus building with one guy and building a partnership that works for you?

Babcock: I dont think that has anything to do with his play, to be honest with you. I think that he is getting to play with good players. I just think for him, the more minutes he earns, the better opportunity is for him. Get comfortable with the size of the players. There will be a lot to handle there tomorrow no different than the game against St. Louis. But its like anything. It comes on an as-earned basis.

Youve said that youve kind of tested him in a lot of ways. That third period against St. Louis, he played more than he has earlier in the season.

Babcock: Hak is running the backend. No different than Smitty did it, if the coach is comfortable, you get out there. If he is uncomfortable, you dont get out there. Its that simple. There is a confidence when theyre watching and they feel If you make good plays, you keep going out. If he starts getting nervous, you dont go out as much. Thats just how simple it is.

The chemistry on the Kerfoot line has that exceed expectations?

Babcock: No, I expected Kerf to be a real good player and Mikheyev to be a real good player. I think Mooresy has done a good job. We need them to be consistent every single night. That is what we are asking gout of them. I thought they did a real good job in the Montreal game. They werent quite as good in the St. Louis game, but the matchups were different, too.

Read more from the original source:
Mike Babcock on William Nylander's start to the season, the challenge vs. Tampa Bay, Patrick Marleau signing in San Jose & Rasmus Sandin's play -...

PARIS--(BUSINESS WIRE)--Regulatory News:

GenSight Biologics (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on discovering and developing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today reported positive proof of GS010 DNA transfer from one eye to the other eye following unilateral intravitreal injection of primates. In a non-clinical study to investigate the local biodistribution of GS010, tissue samples from the non-injected eye of monkeys that had been unilaterally injected with GS010 were found to contain GS010 DNA three months after injection, indicating the expression of the therapeutic gene in the contralateral eye

These results join a growing body of evidence suggesting the two eyes communicate not only in disease, but also in response to treatment, said David J. Calkins, PhD, ODay Professor, Vice Chair and Director for Research Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, United States. With the new understanding these results provide, we can move forward with more precise treatments.

Performed by CiToxLAB France, a leading CRO for preclinical research, the study was initiated by GenSight to investigate potential mechanisms behind the unexpected contralateral effect seen in two of GS010s Phase III trials, REVERSE and RESCUE. As previously reported, both trials, which this year completed the two-year follow-up of patients unilaterally injected with GS010, documented sustained bilateral improvements in LogMAR mean visual acuity. The contralateral effect did not conform to expectations for gene therapies administered to only one eye.

The CiToxLAB study uses a purpose-bred species of monkeys, which is favored by scientists and accepted by regulatory bodies due to physiological similarities with humans. For testing at three months, a control monkey was given an intravitreal injection of saline solution in its right eye and was not injected in its left eye. Three test monkeys were given an intravitreal injection of GS010 in their right eyes and not injected in their left eyes. The dosage of GS010 was calibrated to be the allometric equivalent of that used in the GS010 Phase III trials. Three months after the injection, tissues from the right and left eyes were sampled and tested using a qPCR test which had been validated in a dedicated prior study. The highly sensitive and accurate test contains a protocol that specifically targets a portion of the GS010 DNA and can detect the GS010 DNA matrix.

As expected, the qPCR test did not detect the GS010 DNA in any of the tissue samples from the control monkey unilaterally injected with saline solution. Also as expected, the test was able to detect, and in many cases, quantify the presence of GS010 DNA in tissue samples from GS010-injected right eye. Remarkably the qPCR test was also able to detect, and even quantify, viral DNA vector in the contralateral eye, which had received no injection.

Note: qPCR test used to detect GS010 DNA was validated in a dedicated study conducted prior to the monkey study. The graph depicts the number of monkeys whose tissues contained DNA that were within the sensitivity of the test to detect. In some cases, the levels were above the quantifiable threshold.

DNA was detected and quantified in the anterior segment, the retina, as well as the optic nerve of the non-injected contralateral eye. In addition, DNA was detected and quantified in the optic chiasm, suggesting that the anatomic route taken by the viral vector DNA from the treated eye to the non-treated eye was via the optic nerves and chiasm.

The identification of viral vector DNA in the contralateral uninjected eye is an important observation with broader relevance to the design of gene therapy trials for optic neuropathies, noted Dr. Patrick Yu-Wai-Man, Senior Lecturer and Honorary Consultant Ophthalmologist at the University of Cambridge, Moorfields Eye Hospital, and the UCL Institute of Ophthalmology, London, United Kingdom. Although the non-human primate study was not designed to determine the underlying mode of transfer, the presence of viral vector DNA in the optic chiasm and optic nerve of the contralateral uninjected eye points towards a possible diffusion pathway. Further experimental work will clarify these interesting findings.

We are excited about these scientifically significant results, commented Bernard Gilly, Co-founder and Chief Executive Officer of GenSight. Moreover, they vindicate the companys position that the unexpected bilateral improvements seen in the REVERSE and RESCUE trials have a solid scientific basis. The results help provide a compelling argument in support of GS010s marketing authorization application.

GenSight is working with its panel of scientific experts to prepare the findings for submission to a peer-reviewed journal later this year.

Dr. Yu-Wai-Man will discuss these findings when he presents RESCUE results at the 2019 annual meeting of the American Academy of Ophthalmology in San Francisco, CA:

Session Date: Sunday, October 13Paper Session: OP04 Neuro-Ophthalmology Original PaperSession Time: 2:00 PM to 3:15 PMLocation: South 152Presenter: Patrick Yu-Wai-Man, FRCOphth MBBS PhDPresentation time: 3:00 p.m.

About GenSight Biologics

GenSight Biologics S.A. is a clinical-stage biopharma company focused on discovering and developing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders. GenSight Biologics pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence (MTS) and optogenetics, to help preserve or restore vision in patients suffering from blinding retinal diseases. GenSight Biologics lead product candidate, GS010, is in Phase III trials in Leber Hereditary Optic Neuropathy (LHON), a rare mitochondrial disease that leads to irreversible blindness in teens and young adults. Using its gene therapy-based approach, GenSight Biologics product candidates are designed to be administered in a single treatment to each eye by intravitreal injection to offer patients a sustainable functional visual recovery.

About GS010

GS010 targets Leber Hereditary Optic Neuropathy (LHON) by leveraging a mitochondrial targeting sequence (MTS) proprietary technology platform, arising from research conducted at the Institut de la Vision in Paris, which, when associated with the gene of interest, allows the platform to specifically address defects inside the mitochondria using an AAV vector (Adeno-Associated Virus). The gene of interest is transferred into the cell to be expressed and produces the functional protein, which will then be shuttled to the mitochondria through specific nucleotidic sequences in order to restore the missing or deficient mitochondrial function.

About Leber Hereditary Optic Neuropathy (LHON)

Leber Hereditary Optic Neuropathy (LHON) is a rare maternally inherited mitochondrial genetic disease, characterized by the degeneration of retinal ganglion cells that results in brutal and irreversible vision loss that can lead to legal blindness, and mainly affects adolescents and young adults. LHON is associated with painless, sudden loss of central vision in the 1st eye, with the 2nd eye sequentially impaired. It is a symmetric disease with poor functional visual recovery. 97% of patients have bilateral involvement at less than one year of onset of vision loss, and in 25% of cases, vision loss occurs in both eyes simultaneously. The estimated incidence of LHON is approximately 1,400 to 1,500 new patients who lose their sight every year in the United States and Europe.

About REVERSE and RESCUE

REVERSE and RESCUE are two separate randomized, double-masked, sham-controlled Phase III trials designed to evaluate the efficacy of a single intravitreal injection of GS010 (rAAV2/2-ND4) in subjects affected by LHON due to the G11778A mutation in the mitochondrial ND4 gene.

The primary endpoint will measure the difference in efficacy of GS010 in treated eyes compared to sham-treated eyes based on BestCorrected Visual Acuity (BCVA), as measured with the ETDRS at 48 weeks post-injection. The patients LogMAR (Logarithm of the Minimal Angle of Resolution) scores, which are derived from the number of letters patients read on the ETDRS chart, will be used for statistical purposes. Both trials have been adequately powered to evaluate a clinically relevant difference of at least 15 ETDRS letters between treated and untreated eyes adjusted to baseline.

The secondary endpoints will involve the application of the primary analysis to bestseeing eyes that received GS010 compared to those receiving sham, and to worseseeing eyes that received GS010 compared to those that received sham. Additionally, a categorical evaluation with a responder analysis will be evaluated, including the proportion of patients who maintain vision (< ETDRS 15L loss), the proportion of patients who gain 15 ETDRS letters from baseline and the proportion of patients with Snellen acuity of >20/200. Complementary vision metrics will include automated visual fields, optical coherence tomography, and color and contrast sensitivity, in addition to quality of life scales, biodissemination and the time course of immune response. Readouts for these endpoints are at 48, 72 and 96 weeks after injection.

The trials are conducted in parallel, in 37 subjects for REVERSE and 39 subjects for RESCUE, in 7 centers across the United States, the UK, France, Germany and Italy. Week 96 results were reported in 2019 for both trials, after which patients were transferred to a long-term follow-up study that will last for three years.

ClinicalTrials.gov Identifiers:REVERSE: NCT02652780RESCUE: NCT02652767

About REFLECT

REFLECT is a multi-center, randomized, double-masked, placebo-controlled study to evaluate the safety and efficacy of bilateral injections of GS010 in subjects with LHON due to the NADH dehydrogenase 4 (ND4) mutation.

The trial planned to enroll 90 patients with vision loss up to 1 year in duration and will be conducted in multiple centers in Europe and in the US.

In the active arm, GS010 will be administered as a single intravitreal injection to both eyes of each subject. In the placebo arm, GS010 will be administered as a single intravitreal injection to the first affected eye, while the fellow eye will receive a placebo injection.

The primary endpoint for the REFLECT trial is the BCVA reported in LogMAR at 1-Year post-treatment in the secondaffected/notyetaffected eye. The change from baseline in secondaffected/notyetaffected eyes receiving GS010 and placebo will be the primary response of interest. The secondary efficacy endpoints include: BCVA reported in LogMAR at 2-Years post-treatment in the secondaffected/notyetaffected eye compared to both placebo and the firstaffected eye receiving GS010, OCT and contrast sensitivity and quality of life scales. The first subject was treated in March 2018, and enrolment was completed in July 2019, ahead of schedule.

ClinicalTrials.gov Identifiers:REFLECT: NCT03293524

Excerpt from:
GenSight Biologics Reports Evidence of GS010 DNA Transfer to Contralateral Eye of Primates Unilaterally Injected With GS010 Gene Therapy - Business...

CAMBRIDGE, Mass.--(BUSINESS WIRE)--AVROBIO, Inc. (NASDAQ: AVRO) (the Company) today announced that the first patient has been dosed in the Companys AVR-RD-04 investigational gene therapy program for cystinosis, a devastating lysosomal storage disease, in an ongoing Phase 1/2 clinical trial sponsored by academic collaborators at the University of California San Diego. The gene therapy is derived from the patients own hematopoietic stem cells, which are genetically modified to produce functional cystinosin, a crucial protein that patients with cystinosis lack.

The trial will enroll up to six patients with cystinosis, a rare inherited disease caused by a defect in the gene that encodes for cystinosin. The cystinosin protein enables transport of the amino acid cystine out of lysosomes. When it is absent, cystine accumulates and crystalizes, causing progressive damage to the kidneys, liver, muscles, eyes and other organs and tissues. Cystinosis affects both children and adults; they face shortened life spans and often painful symptoms, including muscle wasting, difficulty breathing, blindness and kidney failure.

Cystinosis is a debilitating and progressive disease, and new treatment options are sorely needed. The current standard of care does not avert deterioration; at best, it can attenuate symptoms. Thats why gene therapy is particularly exciting: It has the potential to change the course of disease -- and the lives of patients -- by addressing the underlying cause of cystinosis, said Birgitte Volck, MD, PhD, President of Research and Development at AVROBIO. We believe we can engineer patients own stem cells so they sustainably produce the functional protein that is needed to prevent a toxic buildup of cystine and halt progression of the disease. We are so pleased that this investigational gene therapy is now in the clinic in collaboration with Dr. Stephanie Cherqui at UC San Diego.

The single-arm trial will enroll four adults and a potential follow-on cohort of two adults or adolescents at least 14 years of age who are currently being treated with cysteamine, the standard of care for cystinosis. If started at an early age and taken on a strict dosing schedule, cysteamine can delay kidney failure. However, the treatment regimen is highly burdensome, with side effects that can be severe and unpleasant, and many patients find it difficult to adhere to this treatment regimen. Even if compliance is high, cysteamine therapy cannot prevent kidney failure or avert other complications.

For people with cystinosis, there are no healthy days. They must take dozens of pills a day, around the clock, just to stay alive. It is a relentless disease and we urgently need new treatments, said Nancy J. Stack, President of the Cystinosis Research Foundation, which supported development of the gene therapy with more than $5.4 million in grants to Dr. Cherquis lab at UC San Diego. We believe that we are now an important step closer to the potential cure that our community has been working toward for many years.

The trials primary endpoints are safety and tolerability, assessed for up to two years after treatment, as well as efficacy, as assessed by cystine levels in white blood cells. Secondary endpoints to assess efficacy include changes in cystine levels in the blood, intestinal mucosa and skin and cystine crystal counts in the eye and skin. Efficacy will also be evaluated through clinical tests of kidney function, vision, muscle strength, pulmonary function and neurological and psychometric function, as well as through assessments of participants quality of life after treatment. The trial is funded by grants to UC San Diego from the California Institute for Regenerative Medicine (CIRM) as well as the Cystinosis Research Foundation.

This investigational gene therapy starts with the patients own stem cells, which are genetically modified so that their daughter cells can produce and deliver functional cystinosin to cells throughout the body. With this approach we aim to prevent the abnormal accumulation of cystine that causes so many devastating complications, said Stephanie Cherqui, PhD, an Associate Professor of Pediatrics at UC San Diego School of Medicine, and consultant to AVROBIO. We have been working toward this trial for years and we are grateful for all the support that brought us to this moment.

About AVR-RD-04

AVR-RD-04 is a lentiviral-based gene therapy designed to potentially halt the progression of cystinosis with a single dose of the patients own hematopoietic stem cells. The stem cells are genetically modified so they can produce functional cystinosin with the aim of substantially reducing levels of cystine in cells throughout the patients body. Before the infusion of the cells, patients undergo personalized conditioning with busulfan to enable the cells to permanently engraft. The Phase 1/2 clinical trial is being conducted under the name CTNS-RD-04 by AVROBIOs academic collaborators at the University of California, San Diego.

About Cystinosis

Cystinosis is a rare, inherited lysosomal storage disorder characterized by the accumulation of cystine in all the cells of the body, resulting in serious and potentially fatal damage to multiple organs and tissues and the shortening of patients life spans. The kidneys and eyes are especially vulnerable; more than 90% of untreated patients require a kidney transplant before age 20. An estimated 1 in 170,000 people are diagnosed with cystinosis.

About AVROBIO, Inc.

AVROBIO, Inc. is a leading, Phase 2 gene therapy company focused on the development of its investigational gene therapy, AVR-RD-01, in Fabry disease, as well as additional gene therapy programs in other lysosomal storage disorders including Gaucher disease, cystinosis and Pompe disease. The Companys plato platform includes a proprietary vector system, automated cell manufacturing solution and a personalized conditioning regimen deploying state-of-the-art precision dosing. AVROBIO is headquartered in Cambridge, MA and has offices in Toronto, ON. For additional information, visit http://www.avrobio.com.

Forward-Looking Statements

This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as aims, anticipates, believes, could, estimates, expects, forecasts, goal, intends, may, plans, possible, potential, seeks, will and variations of these words or similar expressions that are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding the therapeutic potential of our product candidates, the design, commencement, enrollment and timing of ongoing or planned clinical trials, including the ongoing Phase 1/2 trial of the Companys AVR-RD-04 investigational gene therapy, the anticipated benefits of our gene therapy platform, the expected safety profile of our product candidates, timing and likelihood of success of our current or future product candidates, and the market opportunity for our product candidates. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early stage clinical trials may not be indicative of results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented.

Any forward-looking statements in this press release are based on AVROBIOs current expectations, estimates and projections about our industry as well as managements current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more of AVROBIOs product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators, the risk that AVROBIO may not realize the intended benefits of our gene therapy platform, including the features of our plato platform, the risk that our product candidates or procedures in connection with the administration thereof will not have the safety or efficacy profile that we anticipate, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving AVROBIOs product candidates, the risk that we will be unable to obtain and maintain regulatory approval for our product candidates, the risk that the size and growth potential of the market for our product candidates will not materialize as expected, risks associated with our dependence on third-party suppliers and manufacturers, risks regarding the accuracy of our estimates of expenses and future revenue, risks relating to our capital requirements and needs for additional financing, and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIOs actual results to differ materially and adversely from those contained in the forward-looking statements, see the section entitled Risk Factors in AVROBIOs most recent Quarterly Report on Form 10-Q, as well as discussions of potential risks, uncertainties and other important factors in AVROBIOs subsequent filings with the Securities and Exchange Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

Original post:
AVROBIO Announces First Patient Dosed in Phase 1/2 Trial of Gene Therapy for Cystinosis - Business Wire

NEW YORK, Oct. 10, 2019 (GLOBE NEWSWIRE) -- Mustang Bio, Inc. (Mustang) (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, today congratulated City of Hope, a world-renowned independent cancer research and treatment center, on its receipt of $4.1 million in grant awards for a clinical trial of MB-101 (IL13R2-specific CAR T) in combination with nivolumab (commercial name: Opdivo) and ipilimumab (commercial name: Yervoy) in patients with recurrent malignant glioma. The trial, which is now enrolling patients, is the first human study to combine IL13R2 CAR T cells with checkpoint inhibitors, as well as the first to locally deliver CAR T cells with combination treatment with systemic nivolumab treatment.

With nivolumab and ipilimumab products provided by Bristol-Myers Squibb, patients in the randomized Phase 1 trial will receive MB-101 dosed weekly combined with nivolumab, an anti-PD-1 antibody, dosed every other week. Patients on the experimental arm will additionally receive ipilimumab an anti-CTLA-4 antibody and nivolumab, each dosed once 14 days prior to the start of combination therapy with MB-101 plus nivolumab.

To launch the trial, the National Institutes of Health awarded $3.3 million over five years to Behnam Badie, M.D., City of Hopes Heritage Provider Network Professor in Gene Therapy and chief of its Division of Neurosurgery, and Christine Brown, Ph.D., City of Hopes Heritage Provider Network Professor in Immunotherapy and associate director of its T Cell Therapeutics Research Laboratory. Drs. Brown and Badie also received $800,000 from Gateway for Cancer Research.

Our hope is that by combining two powerful immunotherapies CAR T cell therapy and checkpoint inhibitors we can find additional treatments for patients with malignant glioma, who currently have few options, said Brown. In addition, this trial will allow us to conduct liquid biopsies of the cerebrospinal fluid throughout the treatment time to query the central nervous system, furthering our understanding of how checkpoint inhibitors alter the function and persistence of CAR T cells, as well as how they potentially promote endogenous immune responses in the brain.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang, said, We congratulate City of Hope on these prestigious grants, which recognize the extraordinary work of Drs. Badie and Brown in advancing MB-101, which has demonstrated compelling potential to treat glioblastoma multiforme. We are excited to learn more about MB-101s therapeutic potential for patients with recurrent malignant gliomas.

Mustang is the exclusive licensee of City of Hope patents covering its IL13R2-specific CAR T cell therapy.

Additional information about the trial can be found onwww.clinicaltrials.govusing the identifier NCT04003649.

About Mustang BioMustang Bio, Inc. (Mustang) is a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases. Mustang aims to acquire rights to these technologies by licensing or otherwise acquiring an ownership interest, to fund research and development, and to outlicense or bring the technologies to market. Mustang has partnered with top medical institutions to advance the development of CAR T and CRISPR/Cas9-enhanced CAR T therapies across multiple cancers, as well as a lentiviral gene therapy for XSCID. Mustang is registered under the Securities Exchange Act of 1934, as amended, and files periodic reports with the U.S. Securities and Exchange Commission. Mustang was founded by Fortress Biotech, Inc. (NASDAQ: FBIO). For more information, visit http://www.mustangbio.com.

ForwardLooking Statements This press release may contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. Such statements include, but are not limited to, any statements relating to our growth strategy and product development programs and any other statements that are not historical facts. Forward-looking statements are based on managements current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to our growth strategy; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; risks relating to the timing of starting and completing clinical trials; uncertainties relating to preclinical and clinical testing; our dependence on third-party suppliers; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in our SEC filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law.

Company Contact:Jaclyn Jaffe and William BegienMustang Bio, Inc.(781) 652-4500ir@mustangbio.com

Investor Relations Contact:Daniel FerryLifeSci Advisors, LLC(617) 535-7746daniel@lifesciadvisors.com

Media Relations Contact:Tony Plohoros6 Degrees(908) 940-0135tplohoros@6degreespr.com

Read the original:
Mustang Bio Announces City of Hope Receives $4.1 Million in Grant Awards for Recently Opened First-of-Its-Kind Clinical Trial for Patients with...

Visit the News Hub

Mouse study shows immune cells drive brain damage

A neuron containing tangles of tau protein is surrounded by immune cells known as microglia in this computer-generated image. A study from Washington University School of Medicine in St. Louis has found that microglia drive neurodegeneration in diseases, including Alzheimer's disease, that are linked to tau protein. Targeting microglia may help treat such diseases.

Messy tangles of a protein called tau can be found in the brains of people with Alzheimers disease and some other neurodegenerative diseases. In Alzheimers, the tangles coalesce just before tissue damage becomes visible in brain scans and people start to become forgetful and confused.

Now, a new study has found that brain immune cells called microglia which are activated as tau tangles accumulate form the crucial link between protein clumping and brain damage. The research, published Oct. 10 inthe Journal of Experimental Medicine, shows that eliminating such cells sharply reduces tau-linked brain damage in the mice and suggests that suppressing such cells might prevent or delay the onset of dementia in people.

Right now many people are trying to develop new therapies for Alzheimers disease, because the ones we have are simply not effective, said senior authorDavid Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of theDepartment of Neurology. If we could find a drug that specifically deactivates the microglia just at the beginning of the neurodegeneration phase of the disease, it would absolutely be worth evaluating in people.

Under ordinary circumstances, tau contributes to the normal, healthy functioning of brain neurons. In some people, though, it collects into toxic tangles that are a hallmark of neurodegenerative diseases such as Alzheimers and chronic traumatic encephalopathy, a progressive brain disease often diagnosed in football players and boxers who have sustained repeated blows to the head. Holtzman and colleagues previously had shown that microglia limit the development of a harmful form of tau. But the researchers also suspected that microglial cells could be a double-edged sword. Later in the course of the disease, once the tau tangles have formed, the cells attempts to attack the tangles might harm nearby neurons and contribute to neurodegeneration.

To understand the role of microglial cells in tau-driven neurodegeneration, Holtzman, first author and postdoctoral researcher Yang Shi, PhD, and colleagues studied genetically modified mice that carry a mutant form of human tau that easily clumps together. Typically, such mice start developing tau tangles at around 6 months of age and exhibiting signs of neurological damage by 9 months.

Then, the researchers turned their attention to the gene APOE. Everyone carries some version of APOE, but people who carry the APOE4 variant have up to 12 times the risk of developing Alzheimers disease compared with those who carry lower-risk variants. The researchers genetically modified the mice to carry the human APOE4 variant or no APOE gene. Holtzman, Shi and colleagues previously had shown that APOE4 amplifies the toxic effects of tau on neurons.

For three months, starting when the mice were 6 months of age, the researchers fed some mice a compound to deplete microglia in their brains. Other mice were given a placebo for comparison.

The brains of mice with tau tangles and the high-risk genetic variant were severely shrunken and damaged by 9 months of age as long as microglia were also present. If microglia had been eliminated by the compound, the mices brains looked essentially normal and healthy with less evidence of harmful forms of tau despite the presence of the risky form of APOE.

Further, mice with microglia and mutant human tau but no APOE also had minimal brain damage and fewer signs of damaging tau tangles. Additional experiments showed that microglia need APOE to become activated. Microglia that have not been activated do not destroy brain tissue or promote the development of harmful forms of tau, the researchers said.

Microglia drive neurodegeneration, probably through inflammation-induced neuronal death, Shi said. But even if thats the case, if you dont have microglia, or you have microglia but they cant be activated, harmful forms of tau do not progress to an advanced stage, and you dont get neurological damage.

The findings indicate that microglia are the linchpin of the neurodegenerative process and an appealing target of efforts to prevent cognitive decline in Alzheimers disease, chronic traumatic encephalopathy and other neurodegenerative diseases. The compound Holtzman and Shi used in this study has side effects that make it a poor option for drug development, but it could point the way to other compounds more narrowly tailored to microglia.

If you could target microglia in some specific way and prevent them from causing damage, I think that would be a really important, strategic, novel way to develop a treatment, Holtzman said.

Shi Y, Manis M, Long J, Wang K, Sullivan PM, Remolina J, Hoyle R, Holtzman DM. Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model. Journal of Experimental Medicine.Oct. 10, 2019. DOI: 10.1084/jem.20190980

This study is supported by the National Institutes of Health (NIH), grant numbers NS090934 and AG047644; JPB Foundation; and the Cure Alzheimers Fund.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

Read more from the original source:
Targeting immune cells may be potential therapy for Alzheimer's - Washington University School of Medicine in St. Louis