Stanford Expands Gene Therapy Trial for Sickle Cell Disease

Until recently, allogeneic bone marrow transplant served as the only curative opportunity for those with sickle cell disease. Now, gene therapy offers a new potential. Pediatric hematologist Dr. Geetha Puthenveetil is leading the CRISPR-based effort at Rady Children's Health Orange County, and a patient is already seeing the benefits.

A new partnership with the NIH has established the Gene Therapy Immunology and Standards Laboratory, an initiative designed to standardize gene therapy research and accelerate the development of clinical trials and new treatments 👉 https://heyor.ca/wnX5Uc

University of Iowa research helped lay the foundation for a first-in-human UK gene therapy study targeting BBS10-related retinal degeneration. Three pediatric patients have been treated: https://lnkd.in/ep6wvbMD

reNEW researchers have shown that a gene therapy breakthrough can restore heart function in a severe form of inherited heart disease, an incredible advance for children and adults living with this condition. The team, led by Dr James McNamara during his time at the Murdoch Children's Research Institute (MCRI), and published in Nature Cardiovascular Research, delivered a healthy copy of the ALPK3 gene to lab-grown heart tissue and mouse models of genetic cardiomyopathy. The treatment restored heart function and reversed signs of disease. "By delivering a healthy copy of the ALPK3 gene, we were able to repair diseased heart cells and restore heart function. Remarkably, the therapy not only prevented disease in newborn models but also reversed it in adults," said Dr McNamara. "While further work is needed before this approach reaches patients, these findings provide an exciting foundation for the development of targeted treatments for a range of inherited heart conditions,” said reNEW Melbourne node director Professor Enzo Porrello. Read more: https://lnkd.in/gHSUTwkF

𝗦𝗶𝗰𝗸𝗹𝗲 𝗰𝗲𝗹𝗹 𝗱𝗶𝘀𝗲𝗮𝘀𝗲 𝗶𝘀 𝗻𝗼 𝗹𝗼𝗻𝗴𝗲𝗿 𝗼𝗻𝗹𝘆 𝗮𝗯𝗼𝘂𝘁 𝗺𝗮𝗻𝗮𝗴𝗶𝗻𝗴 𝗰𝗿𝗶𝘀𝗶𝘀. 𝗕𝘂𝘁 𝗶𝘀 𝘁𝗵𝗲 𝗲𝗻𝗱 𝗰𝗹𝗼𝘀𝗲? In recent years, gene-based therapies for sickle cell disease have moved from research discussion into clinical reality. These therapies are designed either to edit specific genetic pathways or add functional genetic material so that the patient’s blood-forming stem cells can produce healthier haemoglobin patterns. In 2023, the U.S. FDA approved two cell-based gene therapies for sickle cell disease: Casgevy, which uses CRISPR-based gene editing, and Lyfgenia, which uses a lentiviral vector approach. 𝗧𝗵𝗮𝘁 𝗶𝘀 𝗻𝗼𝘁 𝗮 𝘀𝗺𝗮𝗹𝗹 𝘀𝘁𝗲𝗽. That is hematology, molecular biology, and translational research meeting at the bedside. 𝗕𝘂𝘁 𝗵𝗲𝗿𝗲 𝗶𝘀 𝘁𝗵𝗲 𝗽𝗮𝗿𝘁 𝘄𝗲 𝗺𝘂𝘀𝘁 𝗻𝗼𝘁 𝗶𝗴𝗻𝗼𝗿𝗲: A scientific breakthrough is not the same thing as equal access. Gene therapy is complex. It requires specialized centres, careful patient selection, stem cell collection, conditioning chemotherapy, long-term follow-up, and significant cost. For many patients, especially in low- and middle-income countries where sickle cell disease is most common, access remains a major challenge. So yes, the science is exciting. But the public health question is just as important: How do we make sure that the people who need these therapies most are not the last to receive them? As a hematologist, blood physiologist, and translational researcher, who is invested in sickle cell studies, this is where I believe the future conversation must go. Not just: “Can science cure?” But also: “Can systems deliver?” Because a breakthrough that cannot reach patients is still an unfinished story. #SickleCellDisease #Hematology #GeneTherapy #CRISPR #TranslationalResearch #BloodPhysiology Sources: FDA approvals of Casgevy and Lyfgenia for sickle cell disease in 2023; American Society of Hematology updates on implementation and access; current reviews on gene therapy for sickle cell disease.

The document discusses a new gene therapy treatment developed by researchers at the Murdoch Children's Research Institute in Melbourne, Australia. The treatment aims to reverse a genetic form of heart disease called cardiomyopathy, which affects the heart's ability to pump blood effectively. The treatment involves replacing the faulty disease-causing gene called ALPK3 with a healthy copy, which has been shown to block disease development in young mouse models and restore heart function in adult patient samples. This research is seen as a major step towards a potential cure for genetic cases of cardiomyopathy, which affects around 30 million people worldwide. Current treatment options are limited to heart transplants, medication, and implantable devices, but this new gene therapy could provide an alternative treatment option that could reach thousands of Australian patients in the coming years. #GeneTherapy #Cardiomyopathy #ALPK3 #GeneticHeartDisease #PrecisionMedicine #MolecularMedicine #TranslationalMedicine #Cardiology #MedicalResearch

Red-blood-cell-inspired nanocarriers showed two useful delivery traits: they could evade immune cells and be engineered to target cancer cells. The platform also carried cargo ranging from genetic material and proteins to whole viruses used in gene therapy, and in mice the vesicles circulated to multiple organs with notable accumulation in the lungs.

Excited to share that our work is now published in Blood Immunology & Cellular Therapy: “Referral Variability and Provider Preparedness for Pediatric Sickle Cell Gene Therapy: A National Survey.” The approval of gene therapies for sickle cell disease has transformed what is possible, but having an effective therapy is only part of the equation. Patients must first be identified, counseled, and connected with centers capable of delivering these complex cellular therapies. In this national survey of 138 pediatric hematology/oncology physicians, we found important variation in how providers approach gene therapy referral and preparation: • Referral patterns differed across provider groups, particularly for patients with neurologic complications. • General pediatric hematologists/oncologists reported lower confidence in counseling about differences between gene therapy products. • Pre-referral practices—including HLA typing and α-globin testing—also varied substantially. For me, one of the most important messages from this work is that the pathway to gene therapy begins before a patient reaches the cellular therapy center. As these therapies become increasingly integrated into sickle cell care, closer collaboration between referring hematologists, SCD specialists, and transplant/cellular therapy programs and clearer pre-referral pathways, will be essential to help families receive timely, informed evaluation of all available curative options. I am grateful to my co-authors and collaborators who contributed to this work, and especially grateful to the physicians who participated in the survey and shared their perspectives. 📖 Read the open-access article: https://lnkd.in/gTi65_gD #SickleCellDisease #GeneTherapy #TexasChildrensHospital #StemCellTransplant #BMT #Hematology #PediatricHematology #BCM #GeneEditing #ImplementationScience

A first-in-human pilot trial in sickle cell disease streamlined a major step in gene therapy delivery. In 10 of 11 participants, enough stem cells were collected in a single session, compared with other approved approaches that can require up to five sessions. The genetically modified cells were then returned in an average of seven weeks, versus industry turnaround times that can take as long as six months or longer. No unexpected safety events or adverse effects related to the stem cell modification were reported.

A single injection delivering a healthy ALPK3 gene completely reversed cardiomyopathy in adult mice and restored normal beat strength and rhythm in heart tissue grown from patients’ cells. The preclinical results also suggest this approach might help some other inherited heart diseases, but further safety studies are still needed before human trials.