Posts Tagged ‘space’

While ex vivo CD34-selected allogeneic hematopoietic stem cell transplants (HCTs) are promising treatments for patients with hematologic and myeloid malignancies, they can be limited by delayed immune recovery and increased risk of death not caused by relapse.

A late-breaking abstract presented at the 2024 Transplantation and Cellular Therapy Tandem Meetings investigated a new approach to allogeneic HCT. Investigators of the phase 2 PRAISE-IR study (NCT04872595) explored using a model-based approach to determine the optimal dose of antithymocyte globulin (ATG), which is used to prevent graft-vs-host disease after transplant. Previous studies suggested high ATG exposure might contribute to nonrelapse mortality.

According to Michael Scordo, MD, the model successfully achieved a low posttransplant ATG exposure, and immune reconstitution by day 100 was achieved in 69% of patients, meeting the studys primary end point. Further, the 2-year rates of nonrelapse mortality and relapse were 9% and 13%, respectively, and relapse-free survival and overall survival rates were high at 78% and 86%, respectively.

These findings suggest that using a model to determine the ATG dose for ex vivo CD34-selected allogeneic HCT can lead to improved immune reconstitution and excellent survival outcomes. This approach may help reduce nonrelapse mortality previously observed in other trials and improve the safety and effectiveness of this type of transplant.

In an interview with Targeted OncologyTM, Scordo, bone marrow transplant specialist and cellular therapist at Memorial Sloan Kettering Cancer Center in New York, New York, discussed the findings from this study and their implications for the allogeneic HCT treatment landscape.

Targeted Oncology: What was the rationale or inspiration for the study you presented at the Tandem Meetings?

Scordo: Ex vivo CD34-selected [allogeneic] transplant is one of the many methods of reducing graft-vs-host disease. It uses a myeloablative conditioning platform and integrates ATG, antithymocyte globulin, into that platform to help reduce the risk of rejection. This has been well studied over the years, but 1 of the downsides of this approach is the delayed immune recovery, particularly the T-cell immune recovery that occurs after [allogeneic] transplant with this approach. What we did based on a recent publication that we have from last year was we used a different dosing of ATG to ensure that the T-cell immune recovery after [allogeneic] transplant using ex vivo CD34 selection would be improved.

What are some of the unmet needs in this space?

There are many methods to reduce graft-vs-host disease after transplant CD34 selection. Many of the other methods including posttransplant cyclophosphamide [PTCy], which has now become a standard of care, are out there and should be used in the appropriate setting. In matched donor transplants, ex vivo CD34 selection is one of the methods of being able to use an ablative or intensive conditioning regimen with very low rates of particularly chronic graft-vs-host disease. We saw this as an opportunity to improve on this platform significantly, using a novel approach but a simple approach.

What were the goals of this study?

The primary end point of the study was the ability to improve the CD34 T-cell immune recovery by day 100 after transplant. This was a sort of a validated predictor in other studies. We had key secondary end points that included nonrelapse mortality, relapse rates, progression-free, and overall survival. With the primary end point, we exceeded that end point. With our trial, about 70% of our 56 patients achieved this appropriate immune recovery by day 100, which was significantly higher than our historical numbers had shown.

What were some of the other findings?

Aside from achieving the primary end point, we saw very low rates of nonrelapse mortality at 2 years, estimated at 8%, which is much lower than some of the previously published data using this platform in the last couple of years. [We also saw] low relapse rates [of] about 12% at 2 years and very favorable progression-free and overall survival, which was 80% and 87%, respectively, at 2 years.

What are some of the takeaways?

I look at this as a simple but novel approach to improving on a platform. We have existing platforms that work well, but we can improve them doing well. To community oncologists, I would say that for patients with myeloid malignancies, there are many different types of transplants that can be done safely and effectively. The appropriate choice of a platform really depends on many factors. We can improve on all these platforms individually, including PTCy. [For] ex vivo CD34 selection, I look at this as a method of just improving on what we have already shown to be an effective platform, being able to use dose-intensive chemotherapy or total body radiation to achieve maximal disease control but making the platform safe and tolerable.

Read this article:
New Allo-HCT Approach Boosts Immune Response, Survival - Targeted Oncology

Raiden Pham

Parents of children with rare diseases go to endless lengths to raise funds and awareness for research that might lead to a cure. Now, the story of 4-year-old Raiden Pham has been to the moon. He has an ultra-rare neurodegenerative disease known as UBA5 disorder that UMass Chan Medical School researchers are targeting.

The story of Raidens journey and its message of love, hope and strength is included on an indestructible digital time capsule of art, music, film and history, as part of the Lunaprise Moon Museum Mission, which was onboard the Odysseus spacecraft that landed on the moon Feb. 22.

When we think about gene therapy, or any kind of cure or treatment for these rare diseases, its always considered a moonshot, but thats not the case anymore in todays world, said Tommy Pham, Raidens father. Were willing to do whatever it takes to save my son and kids with UBA5 disorder and hopefully inspire the next generation of rare disease parents to go on this fight and have hope.

Since 2021, the Raiden Science Foundation, founded by Tommy and Linda Pham, of Beaverton, Oregon, on behalf of their son, has raised around $1 million of its $4 million goal, which supports research in UMass Chans Translational Institute for Molecular Therapeutics and other partner institutions.

The research on UBA5 is led by Toloo Taghian, PhD, instructor in radiology in the lab of Heather Gray-Edwards, DVM, PhD, assistant professor of radiology in the Horae Gene Therapy Center.

Dr. Taghian has identified the top two viral vector constructs for UBA5 expression in-vivo, which show great promise in successfully delivering UBA5 gene therapy to the targeted cells. Taghian and her team are now testing their efficacy in correcting the protein malfunction and treating the underlying cause of this disease and will soon initiate toxicology studies to assess their safety.

Working with Raiden Science Foundation to develop a gene therapy for UBA5 has been an impactful journey, said Taghian. The dedication of the Pham family in supporting UBA5 research allows the UMass Chan team to work toward unpacking the basic science underlying this ultra-rare disease in parallel with our gene therapy development program.

How Raidens story got to the moon was a journey of persistent efforts to raise awareness and support by the Phams. In October 2022, Raiden Science Foundation held a gaming charity stream, Kombat4Rare, based on the Mortal Kombat franchise. One of the main characters in Mortal Kombat is Raiden, named after the God of Thunder in Japanese mythology.

The response from the gaming and entertainment community was enthusiastic, and a few months later Tommy Pham was invited to be featured at a charity event in Marina del Rey, California. Dallas Santana, founder of Space Blue, the exclusive curator of the Lunaprise Museum, was touched by Tommys message and told him Raidens story should be included on the Lunaprise Moon Museum to inspire people on Earth.

Noting that it has been more than 50 years since the last American space capsule landed on the moon, Tommy said, We dont have to wait another 50 years for gene therapy. It could be done now in the coming years. We need to figure out a way with all the right stakeholders to unlock gene therapy for so many other kids suffering different rare diseases, not just us.

Donations to support UBA5 gene therapy at UMass Chan can be made here.

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Story of boy with ultra-rare UBA5 disorder being studied at UMass Chan goes to the moon - UMass Medical School

The environment was something of a shift for Drake, who had spent the previous seven years as the medical response director of the Alcor Life Extension Foundation. Though it was the longtime leader in cryonics, Alcor was still a small nonprofit. It had been freezing the bodies and brains of its members, with the idea of one day bringing them back to life, since 1976.

The foundation, and cryonics in general, had long survived outside of mainstream acceptance. Typically shunned by the scientific community, cryonics is best known for its appearance in sci-fi films like 2001: A Space Odyssey. But its adherents have held on to a dream that at some point in the future, advances in medicine will allow for resuscitation and additional years on Earth. Over decades, small, tantalizing developments in related technology, as well as high-profile frozen test subjects like Ted Williams, have kept the hope alive. Today, nearly 200 dead patients are frozen in Alcors cryogenic chambers at temperatures of 196 C, including a handful of celebrities, who have paid tens of thousands of dollars for the goal of possible revival and ultimately reintegration into society.

But its the recent involvement of Yinfeng that signals something of a new era for cryonics. With impressive financial resources, government support, and scientific staff, its one of a handful of new labs focused on expanding the consumer appeal of cryonics and trying anew to bring credibility to the long-disputed theory of human reanimation. Just a year after Drake came on board as research director of the Shandong Yinfeng Life Science Research Institute, the subsidiary of the Yinfeng Biological Group overseeing the cryonics program, the institute performed its first cryopreservation. Its storage vats now hold about a dozen clients who are paying upwards of $200,000 to preserve the whole body.

Still, the field remains rooted in faith rather than any real evidence that it works. Its a hopeless aspiration that reveals an appalling ignorance of biology, says Clive Coen, a neuroscientist and professor at Kings College London.

Even if one day you could perfectly thaw a frozen human body, you would still just have a warm dead body on your hands.

The cryonics process typically goes something like this: Upon a persons death, a response team begins the process of cooling the corpse to a low temperature and performs cardiopulmonary support to sustain blood flow to the brain and organs. Then the body is moved to a cryonics facility, where an organ preservation solution is pumped through the veins before the body is submerged in liquid nitrogen. This process should commence within one hour of deaththe longer the wait, the greater the damage to the bodys cells. Then, once the frozen cadaver is ensconced in the cryogenic chamber, the hope of the dead begins.

Since its beginnings in the late 1960s, the field has attracted opprobrium from the scientific community, particularly its more respectable cousin cryobiologythe study of how freezing and low temperatures affect living organisms and biological materials. The Society for Cryobiology even banned its members from involvement in cryonics in the 1980s, with a former society president lambasting the field as closer to fraud than either faith or science.

In recent years, though, it has grabbed the attention of the libertarian techno-optimist crowd, mostly tech moguls dreaming of their own immortality. And a number of new startups are expanding the playing field. Tomorrow Biostasis in Berlin became the first cryonics company in Western Europe in 2019, for example, and in early 2022, Southern Cryonics opened a facility in Australia.

More researchers are open to longer-term, futuristic topics than there might have been 20 years ago or so, says Tomorrow Biostasis founder Emil Kendziorra.

Here is the original post:
Why the sci-fi dream of cryonics never died - MIT Technology Review