Stem Cell Clinic

Comparison of fludarabine/melphalan (FluMel) with fludarabine … – Nature.com

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Ciurea SO, Kongtim P, Varma A, Rondon G, Chen J, Srour S, et al. Is there an optimal conditioning for older patients with AML receiving allogeneic hematopoietic cell transplantation? Blood. 2020;135:44952.

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Eapen M, Brazauskas R, Hemmer M, Perez WS, Steinert P, Horowitz MM, et al. Hematopoietic cell transplant for acute myeloid leukemia and myelodysplastic syndrome: conditioning regimen intensity. Blood Adv. 2018;2:2095103.

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Bertz H, Potthoff K, Finke J. Allogeneic stem-cell transplantation from related and unrelated donors in older patients with myeloid leukemia. J Clin Oncol. 2003;21:14804.

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Spyridonidis A, Bertz H, Ihorst G, Grllich C, Finke J. Hematopoietic cell transplantation from unrelated donors as an effective therapy for older patients (> or = 60 years) with active myeloid malignancies. Blood. 2005;105:41478.

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Marks R, Potthoff K, Hahn J, Ihorst G, Bertz H, Spyridonidis A, et al. Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies. Blood. 2008;112:41525.

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Passweg JR, Baldomero H, Chabannon C, Basak GW, de la Cmara R, Corbacioglu S, et al. Hematopoietic cell transplantation and cellular therapy survey of the EBMT: monitoring of activities and trends over 30 years. Bone Marrow Transplant. 2021;56:165164.

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Comparison of fludarabine/melphalan (FluMel) with fludarabine ... - Nature.com

NOT-AR-23-022: Request for Information on Themes for the NIAMS … – National Institutes of Health (.gov)

Request for Information on Themes for the NIAMS Strategic Plan for Fiscal Years 2025-2029

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) supports research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. NIAMS is updating its Strategic Plan to help guide the research, training, and information dissemination programs it supports between fiscal years 2025 through 2029. The new Plan will focus on cross-cutting thematic research opportunities that position the Institute to make a difference in the lives of all Americans.Because public input is a crucial step in this effort, the Institute issued a Request for Information (NOT-AR-22-023) and hosted a meeting attended by approximately 160 researchers, patient representatives, and staff from other Federal entities to gain insight into topics that could be included in the new Strategic Plan.

Through this Request for Information, NIAMS invites feedback from researchers in academia and industry, health care professionals, patient advocates and health advocacy organizations, scientific or professional organizations, Federal agencies, and other interested members of the public on the Institutes distillation of the input received to date. Professional societies and patient organizations are strongly encouraged to submit a single response that reflects the views of their entire membership.

Please provide your perspective on the following potential cross-cutting themes, examples, and bold aspirations. NIAMS is particularly interested in suggestions for additional or alternative:

Examples:

Bold Aspirations:

Examples:

Bold Aspiration:

Note: Efforts to identify and reduce health disparities and provide all Americans with equitable access to clinical and epidemiologic studies and healthcare should be considered for NIAMS-funded research projects whenever possible.

Examples:

Bold Aspirations:

Examples:

Bold Aspiration:

Note: Consistent with the note under Health disparities and health equity, studies of lifestyle factors and environmental exposures should include efforts to identify and reduce health disparities and provide all Americans with equitable access to clinical and epidemiologic studies and healthcare whenever possible.

Examples:

Bold Aspiration:

Note: Consistent with the note under Health disparities and health equity, clinical and epidemiologic research should include efforts to identify and reduce health disparities and provide all Americans with equitable access to clinical and epidemiologic studies and healthcare whenever possible.

Examples:

Bold Aspiration:

Examples:

Bold Aspiration:

Note: Training and workforce efforts are essential for the pursuit of all cross-cutting thematic research areas in the new NIAMS Strategic Plan.

Examples:

Bold Aspiration:

Examples:

Bold Aspirations:

Responses to this RFI must be submitted electronically at https://rfi.grants.nih.gov/?s=654a7bc81e7ccb6f7d03d792.

Responses must be received by Monday, January 1, 2024.

Responses to this RFI are voluntary. Do not include any proprietary, classified, confidential, trade secret, or sensitive information in your response. The responses will be reviewed by NIAMS staff, leadership, and Advisory Council members. Individual feedback will not be provided to any respondent. NIAMS will use the information submitted in response to this RFI at its discretion and will not provide comments to any respondents submission. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted.The Government reserves the right to use any submitted information on public NIH websites, in reports, in summaries of the state of the science, in any possible resultant solicitation(s), grant(s), or cooperative agreement(s), or in the development of future funding opportunity announcements.

This RFI is for information and planning purposes only and shall not be construed as a solicitation, grant, or cooperative agreement, or as an obligation on the part of the Federal Government, the NIH, or individual NIH Institutes and Centers to provide support for any ideas identified in response to it. The Government will not pay for the preparation of any information submitted or for the Governments use of such information. No basis for claims against the U.S. Government shall arise as a result of a response to this request for information or from the Governments use of such information.

We look forward to your input and hope that you will share this RFI document with your colleagues.

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NOT-AR-23-022: Request for Information on Themes for the NIAMS ... - National Institutes of Health (.gov)

Dr Hurwitz on Ongoing Investigations of the Use of CAR T-Cell … – OncLive

Michael Hurwitz, MD, PhD, associate professor, internal medicine (medical oncology), Yale School of Medicine, discusses the ongoing investigation into the use of CAR T-cell therapies in patients with solid tumors, such as kidney cancers.

Hurwitz begins by stating that considerations surrounding the use of CAR T-cell therapy in solid tumors, such as renal cell carcinoma (RCC), have been uncertain. The phase 1 COBALT-RCC trial (NCT04438083), which investigated CTX130 allogeneic CRISPR/Cas9engineered CAR T-cell therapy in patients with advanced clear cell RCC, is currently inactive. However, a new agent with similar attributes to the CAR T-cell product investigated in COBALT-RCC is under development and may improve upon the outcomes seen in COBALT-RCC, Hurwitz begins.

Another trial, the phase 1 TRAVERSE trial (NCT04696731), is ongoing at some sites, he explains. This trial involves off-the-shelf CAR T-cell therapy, Hurwitz explains. These modified CAR T cells are engineered to evade the recipient's immune response and eliminate the need for personalized CAR T-cell production, offering a faster turnaround that is crucial for individuals with advanced solid tumors, Hurwitz explains.Traditionally, introducing foreign T cells into the body triggers immune responses, which are addressed by removing human leukocyte antigens, so the body does not recognize the T cells as foreign. In these modified CAR T cells, the endogenous T-cell receptors are also removed, ensuring these cells do not perceive the body as foreign, he expands.

Along with the FDA approvals of CAR T cells for patients with hematologic malignancies, their application in solid tumors is evolving, Hurwitz emphasizes. Ongoing preclinical research aims to engineer safe, specific, and effective CAR T cells, he states.

These innovations with CAR T-cell therapy promise highly targeted, safe cancer treatments for patients with solid tumors, Hurwitz continues. Looking forward, the possibility of synergies between CAR T-cell therapy and other treatments looms, he notes. Although the timing of integrating CAR T-cell therapies into the solid tumor treatment armamentarium is uncertain, combining these products with other agents offers a glimpse into a future where cancer treatment is more effective and personalized.In essence, technological advances in cancer therapy are just beginning to unfold, Hurwitz adds. The future promises innovations and a convergence of technologies to reshape cancer treatment, ushering in an era of hope and healing, he concludes.

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Dr Hurwitz on Ongoing Investigations of the Use of CAR T-Cell ... - OncLive

Fish-like genetic program used to turn human retinal cells into neurons – EurekAlert

image:

Overall, our study provides a proof-of-principle that human glia can be reprogrammed to cells that are capable of making new neurons," said Thomas Reh, PhD, University of Washington, USA. "This opens up an entirely new way to repair the retina in people that have lost neurons to disease or trauma."

Credit: Thomas Reh, PhD

Loss of neurons in in the retina due to trauma or disease leads to vision impairment or blindness, a process which is irreversible in humans. Interestingly, some animals like fish have the built-in ability to regenerate retinal neurons by turning another retinal cell type called Muller glia into neurons. This conversion does not happen spontaneously in humans and other mammals, but new research by Thomas Reh, Juliette Wohlschlegel, and colleagues at the University of Washington, USA, published in the journalStem Cell Reports, shows that human Muller glia can be coaxed into changing identity in the laboratory, which could serve as a potential source of new neurons to treat vision loss.

"Overall, our study provides a proof-of-principle that human glia can be reprogrammed to cells that are capable of making new neurons,said Thomas Reh, PhD, University of Washington."This opens up an entirely new way to repair the retina in people that have lost neurons to disease or trauma."

Muller glia are supportive cells in the retina which help photoreceptors and other retinal neurons to function properly. In some species like fish and birds, Muller glia turn into immature retinal cells upon injury and subsequently generate new retinal neurons. By contrast, Muller glia in the mammalian retina react to injury with scar formation and inflammation without making new neurons. This difference in behavior is based on different genetic programs being activated in fish versus mammalian Muller glia after injury. Artificial activation of a fish-like genetic program can turn mouse Muller glia into retinal neurons according to prior research. However, up until now, it has not been known if the same strategy can be used to convert human Muller glia into neurons. To answer this question, the researchers genetically modified human Muller glia in the lab to switch on neurons-specific genetic programs, as it naturally happens in fish. Indeed, within a week, the genetically modified cells adopted a neuron-like characteristics resembling immature retinal neurons. These findings suggest that human Muller glia can be coaxed into neurons and may serve as a resource to generate new neurons in patients retinas in the future. Of note, Muller glia in this study were derived from immature Muller glia and it remains to be seen if similar approaches can transform adult human Muller glia into neurons, and to what efficiency.

Stem Cell Reports

ASCL1 induces neurogenesis in human Muller glia

30-Nov-2023

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Fish-like genetic program used to turn human retinal cells into neurons - EurekAlert

Sickle Cell Disease and Genetics: Understanding the Cause and… – Sickle Cell Disease News

This content is sponsored by bluebird bio, Inc. (bbb) and is intended for US patient/caregiver audiences 18 years of age and older only. Any other present or future content posted by a contributor, not expressly designated as bluebird bio, Inc.sponsored content, is not associated with bbb.

As a progressive, unpredictable disease, sickle cell is a genetic condition that affects everyone differently, which can make it difficult to understand. Simply learning more about how the body works can help explain the cause of sickle cell. And with a better understanding of how this disease works and how genetics are involved, you can make informed decisions with your doctor about how to navigate treatment.

As the name implies, sickle cell disease involves your cells. Each person has trillions of cells in their body, all working together to perform functions that keep us alive. Within each cell is DNA, the molecule that contains the genetic information for our cells, including genes. Genes provide the instructions for your cells. They help make the proteins that keep us healthy by powering muscles, attacking invading bacteria, or delivering oxygen throughout the body. Since each cell in your body relies on thousands of proteins to work properly in order for the cells to function correctly, your genes are the blueprint, or instruction manual, for your body. When theres a mutation (or change) in a gene, the instructions can cause a cell or protein to not function properly and potentially cause diseasesuch as sickle cell.

Check out the video to learn more about how genes and proteins impact the symptoms and complications of sickle cell.

There are many different types of cells, but with sickle cell disease its the red blood cells, the most common type of cell in your blood, that are affected. These cells are responsible for delivering oxygen throughout the body, which fuels your organs by giving them the energy they need to function. The protein within these cells that performs this function is called hemoglobin, which is made up of beta-globin proteins and alpha-globin proteins. In order for normal adult hemoglobin (HbA) to work properly, there must be a balance of functioning beta-globin and alpha-globin. The HBB gene provides the instructions for these proteins within hemoglobin, and a mutation in that specific gene affects the instructions, causing your body to produce an abnormal form of beta-globin, such as hemoglobin sickle (HbS), which results in a person having sickle cell disease or carrying the sickle cell trait.

Since sickle cell disease affects everyone differently, its important to develop a comprehensive care plan that works for you and your healthcare team. This plan should aim to monitor symptoms, address chronic complications, and manage your overall health. Its also important to build a healthcare team that includes specialists from different areas who can make your care plan work for you. This team should include your primary care doctor but can also include a hematologist (who specializes in diseases of the blood), a genetic counselor (who can help with family planning), and a community health worker (who may be able to assist you with education and day-to-day monitoring by working with local hospitals), among others.

Pain, fatigue, and other unpredictable symptoms of sickle cell can affect many different aspects of your life. The daily tasks of family life, work, and/or school, as well as future plans, can all be impacted by symptoms and complications, whether theyre sudden (acute) or ongoing (chronic). Knowing how to manage these symptoms and complications can help you or your loved ones better navigate sickle cell care.

Progress continues to be made in the treatment of sickle cell disease, but current options mainly help relieve symptoms and require lifelong use. These treatment options include oral medications and infusions, blood transfusions, and, for a limited number of patients, a hematopoietic stem cell transplant (which can lead to a cure; however, they are mostly limited to people who are under the age of 18 and have a matched-related donor available).

There are also developing therapies now being explored to address unmet needs in the management and treatment of sickle cell. One therapy approach being researched is gene therapy,* which is designed to treat sickle cell at the genetic level with the goal of changing the course of the disease.

Taking the time to educate yourself on the genetics of sickle cell is an important step in managing sickle celland remember, youre not alone. Beyond your loved ones and care team, there is an entire sickle cell community, including advocacy organizations, who are here to help. For more information, visit SparkSickleCellChange.com, a website developed by bluebird bio, to stay proactive in sickle cell care and planning for the future.

*Gene therapies for sickle cell are investigational and not FDA approved. Safety and efficacy have not been established.

bluebird bio is a trademark of bluebird bio, Inc.

2023 bluebird bio, Inc. All rights reserved. SCD-US-00280 08/23

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Sickle Cell Disease and Genetics: Understanding the Cause and... - Sickle Cell Disease News

FDA Approves Nirogacestat for Patients With Desmoid Tumors – Targeted Oncology

The FDA has granted approval to nirogacestat for the treatment of adult patients with desmoid tumors.1

Findings from the phase 3 DeFi trial support this approval as in the study, nirogacestat reduced the risk of disease progression or death by 71% compared with placebo among patients with desmoid tumors (HR, 0.29; 95% CI, 0.15-0.55; P < .001).2

This study is the first positive study for a gamma secretase inhibitor in any indication, and it's the largest and the most rigorous and robust clinical trial ever done in desmoid tumor, said Bernd Kasper, MD, PhD, professor, Mannheim University Medical Center, in an interview with Targeted Oncology. Nirogacestat demonstrated rapid, sustained and statistically significant improvements in all primary and secondary endpoints with a manageable safety profile. So it is definitely a candidate for register for registration in this indication. And it will probably be the standard of care for decimo to most in need of systemic therapy.

Among those given nirogacestat (n = 70), the Kaplan-Meier-estimated median PFS was not estimated and patients treated with placebo (n = 72) had a median PFS of 15.1 months (95% CI, 8.4-not estimable). The likelihood of being event-free at 1 year was higher among patients treated with nirogacestat vs placebo, at 85% (95% CI, 73%-92%) and 53% (95% CI, 40%-64%), respectively.

Additionally, event-free survival rates at 2 years were 76% (95% CI, 61%-87%) with nirogacestat and 44% (95% CI, 32%-56%) with placebo, respectively. The confirmed ORR was 41% with nirogacestat vs 8% with placebo (P < .001), and the complete response rates were 7% and 0%, respectively.

The median time to confirm first response was 5.6 months and 11.1 for the investigative vs control arm, respectively, and the median best percent change in target tumor size was -27.1% (range, -100 to 37) vs 2.3% (range, -100 to 47).

Any-grade adverse events (AEs) were observed in 100% of patients in the nirogacestat arm compared with 96% in the placebo arm, with grade 3 or greater AEs observed in 55% vs 17% of patients in the nirogacestat vs placebo arms, respectively.

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FDA Approves Nirogacestat for Patients With Desmoid Tumors - Targeted Oncology

Gene-editing therapy by Vertex and CRISPR poised for FDA approval – The Boston Globe

Its kind of surreal, said Tornyenu, 22, who grew up in Bethlehem, Pa., and participated in a clinical trial at Childrens Hospital of Philadelphia. Im, like, wait, I dont have sickle cell anymore.

The life-changing drug, developed by Boston-based Vertex and its Swiss partner CRISPR Therapeutics, is expected to be approved by the Food and Drug Administration by Friday for people with severe cases of the disease. Called Casgevy, it would usher in a new era not only for those with sickle cell but also for medicine: The drug would be the first gene-editing therapy authorized by US regulators, and uses a tool called CRISPR.

The likely approval Casgevy was cleared by British regulators last month raises both the promise of cures for diseases as well as the ethical concerns that come with the power to manipulate the building blocks of human life. With an expected price tag in the seven figures, it also touches on issues of equity in medicine.

Sickle cell primarily afflicts people of African descent. Research on the disease languished for decades, which many experts blame on structural racism, particularly in funding.

For Tornyenu, Casgevy has meant an end to the searing pain crises that caused her to miss a week of classes every month as a high school senior. After getting the treatment, she took the spring semester off from Cornell to recover from the debilitating effects of chemotherapy that made room in her blood marrow for gene-edited cells.

But now she no longer dreads the arrival of cold weather, which would often induce excruciating pain in her hips and legs. A senior at Cornell, she has a job lined up as a consultant at PricewaterhouseCoopers in Boston after graduation.

Im very hopeful [Casgevy] will be approved, she said, because I dont know what I would have done otherwise.

The gene-editing method that became known as CRISPR was first reported in a landmark 2012 paper by American biochemist Jennifer Doudna of the University of California, Berkeley, and French microbiologist Emmanuelle Charpentier of the Max Planck Institute for Infection Biology. They would share the 2020 Nobel Prize in chemistry for their work on the tool.

Sickle cell was an obvious choice for scientists to tackle with CRISPR. It was the first human disorder understood on a molecular level, its underpinnings explained in a landmark 1949 paper written by the future two-time Nobel laureate Linus Pauling. Yet progress against the disease was slow for decades afterward.

Sickle cell affects hemoglobin, the oxygen-carrying protein in red blood cells. It causes the round, flexible blood cells to deform into a sickle shape and stick to vessel walls. That deprives tissues of oxygen, causing crushing pain that can often only be relieved with opioids and blood transfusions.

Sickle cell can also lead to strokes, damage organs, and cause early death. A 2019 study in JAMA Network Open estimated the life expectancy of adults with sickle cell in the US is 54 years, about 20 years shorter than the general population.

In a clinical trial, Casgevy demonstrated remarkable results. The medicine completely relieved 29 of 30 sickle cell patients of debilitating episodes of pain for at least one year among trial participants who were followed for at least 18 months, according to Vertex. The patients received a one-time intravenous infusion of edited stem cells that flipped a genetic switch to restore their blood cells ability to carry oxygen throughout their bodies.

This is what a potential cure looks like, said Dr. Stephan Grupp, chief of the Cellular Therapy and Transplant Section at Childrens Hospital of Philadelphia. He was the principal investigator at the trial site where Tornyenu got Casgevy and was paid by Vertex to help organize the study at locations across the US.

About 100,000 Americans, most of them Black or Hispanic, are believed to have sickle cell. The Vertex-CRISPR treatment was geared for those with severe and repeated pain crises, roughly 20,000 people in the US. As of 2021, almost 8 million people around the world live with sickle cell, according to the Institute for Health Metrics and Evaluation at the University of Washington in Seattle.

The FDA has approved four medicines for the disorder, but none has been remotely as effective as Casgevy, which is expected to cost more than $1 million for a one-time infusion in the US, according to experts. (No price has been announced in the United Kingdom.) Sickle cell can be cured with a bone-marrow transplant, but few patients have compatible donors.

Patients are already inquiring about Casgevy, said Dr. Sharl Azar, a hematologist at Massachusetts General Hospital and medical director of its Comprehensive Sickle Cell Disease Treatment Center. He said he is eager to see whether the FDA clears it, how broad the approval would be, and whether Medicare and Medicaid would cover it.

Theres a lot of unknowns that were looking forward to working out in the coming months, he said. But I think everyone, from patients to providers, recognizes that this is a big deal.

Rahman Oladigbolu, a 52-year-old Harvard-educated filmmaker in Brockton, is among local patients interested in Casgevy. He has had six joints his hips, shoulders, and knees surgically replaced since 2000 because of damage from sickle cell. He walks with a cane at times, often gets lightheaded, and takes opioids to relieve persistent pain.

When Oladigbolu was growing up in Nigeria, his grandmother would take him to traditional medicine men and medicine women who prescribed herbs and potions, some of which they rubbed into his aching limbs after cutting him with a razor blade. He moved to the US when he was 28 and currently takes a sickle cell drug called crizanlizumab, which reduces his pain but doesnt eliminate it.

Pursuing a cure has been like a side job all my life, said Oladigbolu, who receives treatment at Boston Medical Center.

CRISPR-based treatments will likely be approved for other disorders in the coming years, experts say, although its hard to predict for what and when. Researchers, including scientists at multiple biotech companies and hospitals in Massachusetts, are studying the potential of gene editing for a variety of diseases, from ALS to forms of cancer.

There will be other gene-editing therapies, certainly, but each disease is different, said Dr. Stuart Orkin, a researcher at Dana-Farber Cancer Institute and Boston Childrens Hospital who in 2008 helped identify the gene that Casgevy snips to treat sickle cell. For some diseases, its not clear what to edit. People will argue about whats the right target. Each one is a special case.

Gene editing has also raised ethical concerns. In 2018, a Chinese scientist, He Jiankui, was widely condemned when he announced that he used CRISPR to edit DNA in human embryos to try to make them immune to HIV. The experiment sparked fears that He had opened the door to creating so-called designer babies children whose genetic makeup is altered to produce desired traits.

Dr. George Q. Daley, dean of Harvard Medical School, was among those who said Hes experiment raised the specter of a Brave New World of eugenics. Casgevy, he said recently, is completely different. The modifications it makes to DNA only helps sickle cell patients and cannot be passed on to their children.

Daleys bigger worry concerns access to Casgevy. While wealthy countries like the US have hospitals and doctors capable of preparing patients for the treatment and administering it, he said, millions of people with sickle cell in sub-Saharan Africa dont have those options.

This is a triumph of modern biomedicine, he said. The major ethical concerns now are issues of cost and equitable distribution.

Casgevy isnt the only gene-based medicine on the horizon for sickle cell. The Somerville biotech Bluebird Bio hopes the FDA approves a so-called gene therapy, lovo-cel, by Dec. 20. It also proved remarkably effective in clinical trials.

Unlike Casgevy, which cuts a gene, lovo-cel adds a modified gene into a patients DNA to enable blood cells to deliver oxygen. The FDA has approved at least eight gene therapies for mostly rare diseases since 2017.

Both Casgevy and lovo-cel are expected to be breathtakingly expensive. That has renewed questions about whether the health care system can afford such cutting-edge medicines.

Still, the Institute for Clinical and Economic Review, or ICER, an independent Boston-based drug-pricing watchdog, estimates that either drug could cost nearly $2 million and be worth it, given the cumulative costs of treating sickle cell over a lifetime and the benefits the new approaches would bring to patients and families.

Casgevy, which was called exa-cel in clinical trials, works by editing a patients bone marrow stem cells to make high levels of fetal hemoglobin the healthy, oxygen-carrying form of hemoglobin produced during fetal development that is replaced by adult hemoglobin soon after birth.

Unlike adult hemoglobin, fetal hemoglobin resists forming a crescent shape in sickle cell patients, and scientists have long searched for a way to restart it. The researchers behind Casgevy solved the problem by editing a gene called BCL11A, which regulates fetal hemoglobin.

The treatment involves multiple steps over several months. Patients must donate stem cells to be modified at a laboratory. Then donors have to undergo a grueling regimen of chemotherapy to make room in their bone marrow for the genetically altered cells. Finally, the patients get the cells back through a single infusion.

Dr. David Altshuler, Vertexs chief scientific officer, acknowledged that the gene-editing treatment is extremely complex and resource intensive. He said Vertex is researching the possibility of developing a pill that could do what Casgevy does without gene editing. (Vertexs business partner for Casgevy, CRISPR Therapeutics, is based in Zug, Switzerland, but has most of its workforce in Boston.)

FDA officials have raised concerns about the possibility that Casgevy could inadvertently change patients DNA beyond the targeted disease so-called off-target editing. Dr. Daniel E. Bauer, a staff physician at Dana-Farber Cancer Institute and Boston Childrens Hospital, told an FDA advisory panel on Oct. 31 that Casgevy contains hundreds of millions of edited cells and one could undoubtedly go off target and cause leukemia. But he described the risk as modest given the benefits of the treatment.

Altshuler said recently that there is no evidence to date of off-target editing, but it is important to be humble and to continue to follow patients. Vertex and CRISPR have pledged to follow trial participants for 15 years to make sure they stay healthy.

Tornyenu, the Cornell student, says she considers Casgevy a miracle and would celebrate Dec. 8 every year if the FDA approves the drug that day.

For lack of a better term, she said, its a big FU to sickle cell.

Jonathan Saltzman can be reached at jonathan.saltzman@globe.com.

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Gene-editing therapy by Vertex and CRISPR poised for FDA approval - The Boston Globe

Major Breakthrough: UofM Research Team 3D Prints Heart Valves – Mirage News

Credit: CHU Sainte-Justine

In a breakthrough in pediatric cardiac science, Canadian researchers have successfully produced a bio-ink that could someday be used to print functional, durable heart valves, offering hope for improving the prognosis of children with heart defects.

The discovery of a way to 3D print functional heart valves was made at the CHU Sainte-Justine Research Centre by Universit de Montral assistant medical professor Houman Savoji and his PhD student Arman Jafari.

The results of their research are published in the journal Advanced Functional Materials.

Tissue engineering can be used to create living tissues and organs by combining biomaterials with cells. Unlike mechanical heart valves, engineered biomimetic valves could develop and grow with the recipients. Such tissues and organs could someday be manufactured with a 3D printer, with the right bio-ink such as that developed by Savoji and his colleagues.

Houman Savoji and Arman Jafari

Credit: CHU Sainte-Justine

"My team has shown that an ink composed of polyvinyl alcohol, gelatin and k-carrageenan can be used to print heart valves that open and close correctly and has in-vitro and in-vivo biocompatibility and anti-thrombogenic properties," he explained. "They function well in a physiological environment like that of the human body, in both adult and children's sizes."

This compound also provides a structure (called a "scaffold") in which stem cells can potentially grow until they are replaced by a fully living tissue. Better still, in laboratory tests the valves generated fewer adverse effects than the mechanical or animal valves currently used in patients.

"These results suggest that our valves may be associated with a lower risk of complications than those currently used in transplants," said Jafari. "And since these are biomimetic artificial tissues, they can potentially grow with a transplanted child, limiting the need for repeat surgery."

Over the next few years, the scientists plan to pursue their research through in vivo trials, with the ultimate goal of seeing this technology one day be made available for use in a real-life, surgical setting.

Credit: CHU Sainte-Justine

Credit: CHU Sainte-Justine

Credit: CHU Sainte-Justine

"Formulation and evaluation of PVA/gelatin/carrageenan inks for 3D printing and development of tissue-engineered heart valves," by Aman Jafari et al, was published Oct. 10, 2023 in Advanced Functional Material. Funding was provided by the Fonds de recherche du Qubec - Sant, the Natural Sciences and Engineering Research Council of Canada, the TransMedTech Institute, the CHU Sainte-Justine Research Centre and Universit de Montral. The Savoji lab also benefits from equipment funded by CHU Sainte-Justine Foundation. Arman Jafari also received a doctoral scholarship from the FRQS and a bursary of excellence from Universit de Montral's Faculty of Medicine.

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Major Breakthrough: UofM Research Team 3D Prints Heart Valves - Mirage News

Science Talk – I survived cancer as a child and now I’m working to … – The Institute of Cancer Research

Image: Andrew Wicks in the lab at The Institute of Cancer Research. Credit: Andrew Wicks.

I still remember getting my diagnosis, even though it was all a bit of a whirlwind. Within a couple of days, Id gone from having a cough to having cancer. These things come at you fast!

At 12, I was very active and loved sports. That summer, I spent most of my time playing football or rugby, or doing athletics at school. I developed a persistent cough, but because I seemed so well otherwise, my family and I didnt think much of it. When the antibiotics the doctors had given me didnt work and I was sent to the local hospital for a chest X-ray, we assumed an infection was to blame.

Instead, the X-ray revealed a visible tumour the size of an orange in the lymph nodes around my lungs. Suspecting lymphoma, the doctors put me in an ambulance and sent me to Great Ormond Street Hospital, a childrens hospital in London. There, I had a bone marrow biopsy, which showed that I actually had acute lymphoblastic leukaemia (ALL).

ALL is a type of blood cancer that results from the bone marrow making too many immature white blood cells called lymphocytes. Many of the initial symptoms, including fatigue, frequent infections, and a fever, are nonspecific, but its important to start treatment immediately. Without treatment, the disease progresses very quickly and is fatal.

I didnt really digest the news at first. I was too numb, too shocked to be scared. I just went into autopilot and tried to adapt to the situation as it rapidly changed. However, I vividly remember my parents being scared and upset. They were devastated by my diagnosis.

Luckily, because leukaemia is the most common type of cancer in children, and ALL is the most common type of leukaemia at this age, doctors know how to treat it.

Image: Andrew aged 12, before receiving the ALL diagnosis. Credit: Andrew Wicks.

I started on high-dose chemotherapy, which was very intense. It made me feel nauseated and fatigued, and it weakened my immune system. For a year, long hospital stays and my low immunity meant that I was unable to go to school or anywhere else really. Most of the time, I felt too poorly to leave the house anyway. But I missed seeing my friends, having a social life and playing sports. My mum stopped working so that she could stay at home with me and take care of me, and my dad took a lot of time out from work so that he could be at my hospital visits.

My trips out were mainly to the hospital, which I visited at least once a week. I underwent procedures such as bone marrow biopsies and lumbar punctures, and I received chemotherapy as an outpatient there. Now, as an adult, I can reflect on how tough the treatment was, but at the time, I tried to keep a positive mindset, focusing on taking each day at a time and getting through it. To me, each treatment or hospital visit meant that I was taking a step closer to the finish.

Once I moved onto maintenance therapy, I was able to return to school, and my mum went back to work. The side effects of the treatment were more manageable, and my life started to feel a bit closer to normal. I was able to see my friends again and to go into town. But then, in the third year of my treatment, my ALL relapsed. I felt very dispirited because treatment had been going so well, but my doctors still had hope.

I needed to try a new form of treatment, so they recommended that I undergo a stem cell transplant. I had to have high-dose chemotherapy and radiotherapy to deplete my immune system before the transplant. Then I had to take immunosuppressive drugs to prevent my immune system from rejecting the donor cells and to prevent the donor cells from attacking healthy cells in my body.

Again, I had to be really careful to protect myself from infection while my immunity was low. I ended up taking some of my GCSE exams while in hospital for treatment because I was stubbornly determined not to let it disrupt the normality that had seemed so close. But it felt like a step backwards.

Thats why, when I had finally the long-desired appointment in which they told me that I was done with treatment and would only need to see the team again for checkups, my first feeling was just incredible relief. Were here, I remember thinking. Weve made it! It was such a happy moment for my family. My parents, two brothers and sister had all gone through it too. My diagnosis and treatment were tough for everyone.

Image: Andrew receiving stem cells in the hospital. Credit: Andrew Wicks.

The support and care I received from hospital staff and my family were incredible, and I cant express enough how much that helped me.

With hindsight, I was probably quite an annoying patient! Seeing lots of other people with cancer and hearing about many different treatments meant that I always had lots of questions. What is this drug? I would ask. How does it work? I took part in clinical trials during my treatment and, even as a young patient, I was intrigued by how research leads to new treatments.

Three years after completing treatment, I chose to study biology as an undergraduate. Learning about cancer in detail the different types of the disease and how it develops and progresses furthered my interest, and I went on to complete a Masters degree focused on cancer drug resistance. Wanting to get some research experience and learn even more about cancer, I joined The Institute of Cancer Research, London, as a Scientific Officer (technician) in Professor Chris Lords labin the Division of Breast Cancer Research.

I learned a lot during this time from my colleagues, who are among the leaders in their field. I knew that, given the expertise and breadth of knowledge in the team, there would be nowhere better for me to learn and undertake my own independent research project.

I am now in the fourth year of my PhD here at The Institute of Cancer Research (ICR). Supervised by Professor Lord and Professor Andrew Tutt, Head of the Division of Breast Cancer Research and Director of the Breast Cancer Now Toby Robins Research Centre at theICR, I am working on a project investigating PARP inhibitors. In particular, I am studying how tumour cells react and change when exposed to these agents, and how these changes might confer drug resistance. The long-term aim is being able to prevent or treat this resistant disease.

This years ICR Christmas fundraising appeal features the story of Tommy Edwards, a seven-year-old who is currently responding well to treatment for ALL, the same type of cancer I had.

Tommys parents, Jo and Chris Edwards, have set up a charity called Prevent ALL, which is funding work by the highly-honoured Professor Sir Mel Greaves, Founding Director of the ICRs Centre for Evolution and Cancer. Professor Greaves research shows that leukaemia, including ALL, may be preventable, and his team is working towards developing simple and safe interventions to stop the disease from developing.

All of us at the ICR are incredibly grateful for the support we receive from our amazing family charity partners like Prevent ALL. Without them, a lot of the work we do would not be possible.

Cancer is hard for everyone, including family members. In my experience, its important, where possible, to have moments where the focus on the disease is temporarily put to the side and you are just a family, as you were before the diagnosis. I hope that Tommy and his family have the opportunity to do just that this Christmas.

We are world-leaders in the study of cancer in children, teenagers and young adults and have made huge strides over the past decade in understanding the causes and improving treatments. With your support, we can make the hope of safer, kinder and more effective treatments a reality for these children. Help cure more children with cancer, more kindly.

Make a monthly donation today

Image: Tommy Edwards. Credit:ICR/John Angerson.

We still have much to learn about childhood cancer, but it is clearly not the same as adult cancer. Ideally, we should be treating it accordingly. We need treatments that are targeted to children and more appropriate for their needs.

Although the priority is, rightly, to provide treatments that are as effective as possible, in an ideal world, they would be much kinder too.

While I feel exceedingly fortunate that my treatment was successful, the debilitating side effects cost me at least a year of my childhood. Kinder treatments could allow children to go to school, see their friends and generally have a life outside of their illness. I believe that improving the quality of life for children with cancer is nothing short of essential.

At the ICR, Ive seen with my own eyes the strong connection between work in the labs and the resulting benefits for patients. The translational aspect of the ICRs work means that it has a direct impact on people. I find it very motivating to work at an institution that is so well-placed to change clinical practice for the better.

Although I dont work in the field of paediatric cancer, when I think back to my childhood, it makes me feel really positive about my career choice. Knowing that my current research might go on to help others who find themselves facing a cancer diagnosis means that I look forward to Monday mornings.

Im hopeful that, one day, outcomes can be improved for everyone living with cancer, and Im proud to be contributing to this mission. The important thing is that we keep going.

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Science Talk - I survived cancer as a child and now I'm working to ... - The Institute of Cancer Research