Researchers from Penn Medicine have developed a new targeted approach that modifies viral vectors and inhibits toxicities in the sensory neurons of dorsal root ganglia (DRG) that commonly occur following the use of gene therapy for neurological diseases.
This strategy will likely have several important research and clinical implications, as investigators in the field have worked tirelessly for years to develop safer and more effective gene therapies for neurological disorders. We believe that this new approach could improve safety in gene therapy universally, said lead author Juliette Hordeaux, DVM, Ph.D., senior director of Translational Research in Penns Gene Therapy Program, in a statement.
Many gene therapies use viral vectors, but these vectors can have adverse neurological effects. While these toxicities have not yet been observed in humans, nonhuman primate studies using adeno-associated viral (AAV) vectors to deliver corrected genes via the spinal cord fluid have shown issues of axonal degeneration in spinal cord and peripheral nerve tracts. In these studies, the cause of the issues led back to the DRG, comprising a cluster of neural cells found on the outside of the spinal cord that are responsible for delivering sensory messages.
In a recent paper published in Science Translational Medicine, Dr. Hordeaux and colleagues found a way of modifying these vectors so they ultimately avoid these dangerous side effects. They first found that the toxicities appear to come from overexpression of a transgene in cells in the DRG.
The researchers altered a transgene with a microRNA target that was designed to reduce transgene expression levels in the DRG. Ultimately, this modification eliminated over 80% of the transgene expression and resulted in drastic toxicity reduction in the studied primates
We believe it is a safe, straightforward way to ameliorate the safety of AAV therapy for the central nervous system, said Hordeaux about the studied modification. This approach could be used to design other gene therapy vectors to repress transgene expression in the cell types that are affected by the toxicity and not others, which is critical, because you need the expression everywhere else to effectively treat the disorder.
Senior author of the paper was gene transfer expert James M. Wilson, MD, Ph.D., professor of Medicine and Pediatrics in Penns Perelman School of Medicine. Dr. Wilson, who left Solid Biosciences two years ago. Dr. Wilson has been discussing the potential adverse neurological effects of AAV vectors for several years.
Drs. Hordeaux and Wilson injected vectors with and without a microRNA target miRNA183 in mice and primates in the new study. The administration of unaltered AAV vectors led to robust delivery of the gene into target tissue as well as toxicities in DRG neurons. These effects occurred without impacting transduction in elsewhere in the brain, according to histological analyses conducted up to 90 days later.
The authors of the study suggest the toxicity of DRGs likely occur in a gene therapy relying on high vector doses or direct vector delivery into the fluid of the spinal cord. We were concerned about the DRG pathology that was observed in most of our nonhuman primate studies, noted Wilson. This modified vector shows great promise to reduce DRG toxicity and should facilitate the development of safer AAV-based gene therapies for many central nervous system diseases.
Continue reading here:
New Targeted Approach Could Prevent Toxicities Associated with Neurological Gene Therapies - BioSpace
- Seeking a sickle cell cure: 12-year-old in DC is 1st patient in US to get new gene therapy - NBC Washington - May 24th, 2024
- Evotec makes 'strategic exit' from gene therapy as part of wider shake-up - Fierce Biotech - May 24th, 2024
- Eight Philadelphia biotech companies spearheading the industry - Labiotech.eu - May 24th, 2024
- Evotec shuts down gene therapy business in light of Q1 2024 loss - Pharmaceutical Technology - May 24th, 2024
- NHS investment critical to drive cell and gene therapy research - Clinical Trials Arena - May 24th, 2024
- Argentinian couple moves to US to allow their toddler to join gene therapy trial - The Guardian US - May 24th, 2024
- Narayan Discusses Bladder Preservation and the Role of Gene Therapies in NMIBC - OncLive - May 24th, 2024
- Shaw Prize awarded to 2 scientists for work in SCD gene therapies - Sickle Cell Disease News - May 24th, 2024
- Local cell and gene therapy sector reeled in $7.6B in private investment capital in last five years - Philadelphia Business Journal - May 24th, 2024
- Are Mandatory Diversity Plans Working for Adoptive Cell Therapies? - Syneos Health - May 24th, 2024
- Flexibility of alternative trial designs crucial for cell and gene therapy research - Clinical Trials Arena - May 24th, 2024
- New viral carrier shows promise for brain-targeted gene therapies - Huntington's Disease News - May 24th, 2024
- Cell & Gene Therapy Outsourcing - Contract Pharma - May 24th, 2024
- Gene therapy repairs spinal discs to relieve back pain - New Atlas - May 24th, 2024
- From cell collection to commercial contracting: Advancements in cell & gene therapy manufacturing (Part II) - FiercePharma - May 24th, 2024
- Swedish neurologists warn ALS patients may have to self-pay for new gene therapy - EURACTIV - May 24th, 2024
- Otoferlin Gene Therapy: Positive Results for Genetic Deafness - RegMedNet - May 24th, 2024
- Cell Therapy Weekly: New FDA Approval for Breyanzi - RegMedNet - May 24th, 2024
- CAR T cell therapy for pediatric brain cancer warrants further study - Medical Xpress - May 24th, 2024
- Dosing paused in Pfizer DMD gene therapy trial after patient death - Muscular Dystrophy News - May 14th, 2024
- Astellas CEO Q&A (Part 1): There Is No Playbook on Cell and Gene Therapies - MedCity News - May 14th, 2024
- Bluebird: Cells collected from 1st sickle cell patient having... - Sickle Cell Disease News - May 14th, 2024
- Regeneron Gene Therapy Reaches New Heights In Restoring Hearing - Scrip - May 14th, 2024
- Young participant in Pfizer's DMD gene therapy trial dies - Fierce Biotech - May 14th, 2024
- Boy Dosed with Pfizer DMD Gene Therapy Dies a Year after Phase II Trial - Genetic Engineering & Biotechnology News - May 14th, 2024
- Gene therapy trials treat inherited blindness and deafness - DW (English) - May 14th, 2024
- Deaf girl is cured in world first gene therapy trial - The Independent - May 14th, 2024
- beyond-the-lab-cell-and-gene-therapy - Drug Target Review - May 14th, 2024
- Child who was born deaf can now hear whispers and parents clapping for first time thanks to 'mind-blowing' gene therapy - New York Post - May 14th, 2024
- White Paper: Navigating the regulatory path of CRISPR-based therapeutics 13 May 2024 - SelectScience - May 14th, 2024
- Krystal Biotech touts topical gene therapy uptake, plots overseas launches - FiercePharma - May 14th, 2024
- Pharming uproots angioedema gene therapy collab with Orchard - Fierce Biotech - May 14th, 2024
- Deaf toddler playing piano and dancing after world-first gene therapy - The Telegraph - May 14th, 2024
- New gene therapy allows deaf child to hear DW 05/09/2024 - DW (English) - May 14th, 2024
- Our Mission at Voyager Therapeutics: Define the Future of Neurogenetic Medicines - BioSpace - May 14th, 2024
- Gene therapy provision would make life-saving treatment more accessible and equitable - Star Tribune - May 14th, 2024
- British girl's hearing restored in pioneering gene therapy trial - Sky News - May 14th, 2024
- ASGCT24: Translational Research Powering Potentially Transformative Therapies - BioSpace - May 14th, 2024
- Advancing Delivery of AAV Vector-Based Gene Therapies Using Bispecific Antibodies (ASGCT 2024) - BioPharm International - May 14th, 2024
- Krystal Biotech Inc (KRYS) Reports Strong Q4 and Full Year 2023 Financial Results - Yahoo Finance - February 27th, 2024
- New sickle cell gene therapies are a breakthrough, but solving how to pay their high prices is a struggle - CNBC - February 27th, 2024
- 10 gene therapy companies you should know about - Labiotech.eu - February 27th, 2024
- Former Penn employee sues Gene Therapy Program director, alleging 'unethical and illegal conduct' - The Daily Pennsylvanian - February 27th, 2024
- Gene therapy can't cure deafness because it doesn't need to be cured - The Philadelphia Inquirer - February 27th, 2024
- Fetal surgery expert Tippi MacKenzie shifts to in-utero gene therapy - STAT - February 27th, 2024
- Therapeutic Solutions International Files Patent on Facilitating Effects of JadiCells on Gene Therapy Mediated Cell ... - Business Wire - February 27th, 2024
- CU Anschutz Set to Launch Gene Therapy Trials for Heart Disorder - University of Colorado Anschutz Medical Campus - February 27th, 2024
- ICH targets cell and gene therapies, real-world data as topics ripe for harmonization - Regulatory Focus - February 27th, 2024
- Encoded Therapeutics Announces UK CTA Approval for Dravet Syndrome Gene Therapy Candidate ETX101 - Business Wire - February 27th, 2024
- Voyager Therapeutics Announces Selection of Gene Therapy Development Candidate for Friedreich's Ataxia in ... - GlobeNewswire - February 27th, 2024
- Therapeutic Solutions International Files Patent on Facilitating Effects of JadiCells on Gene Therapy Mediated Cell ... - The Bakersfield Californian - February 27th, 2024
- Ring Therapeutics, a Flagship gene therapy startup, lays off 20% of staff - STAT - February 27th, 2024
- Ed Silverman on new gene therapies, biosimilars, coffee, and more - STAT - STAT - February 27th, 2024
- Combatting HIV using gene therapy - Drug Target Review - February 27th, 2024
- NCDHHS working with federal government on increasing access to sickle cell disease treatment - WECT - February 27th, 2024
- Cell Therapy Weekly: FDA Approves First Cell Therapy For Solid Tumors - RegMedNet - February 27th, 2024
- Rejuvenate Bio Announces Gene Therapy-Mediated Partial Reprogramming Extends Lifespan and Reverses Age ... - Business Wire - February 27th, 2024
- New sickle cell therapy uses gene editing at MUSC | Health | postandcourier.com - The Post and Courier - February 27th, 2024
- Long-term and real-world safety and efficacy of retroviral gene therapy for adenosine deaminase deficiency - Nature.com - February 18th, 2024
- Gene therapy, blood transfusions, stool monitoring: The Sydneysiders trying to escape death - Sydney Morning Herald - February 18th, 2024
- Not too late to repair: gene therapy improves advanced heart failure in animal model - Baylor College of Medicine | BCM - February 18th, 2024
- Direct Administration of CRISPR-Cas9: Tools for Cell and Gene Therapy - Forbes - February 18th, 2024
- Gene therapy's promise seen in its success for AADC deficiency - AADC News - February 18th, 2024
- First Patient Randomized in AskBio Phase II Gene Therapy Trial for Congestive Heart Failure Treatment - Diagnostic and Interventional Cardiology - February 18th, 2024
- FDA to review expanded use of Sarepta Duchenne gene therapy - Yahoo Finance - February 18th, 2024
- How gene therapy can help treat a rare blood disorder - KUTV 2News - February 18th, 2024
- CRISPR gene therapy Casgevy secures approval in Europe - Pharmaceutical Technology - February 18th, 2024
- FDA Updates for the Week of Feb. 12, 2024: New Approvals, an Extended Review and Goal Dates Set - Managed Healthcare Executive - February 18th, 2024
- First Patient Randomized in AskBio Phase II Gene Therapy Trial for Congestive Heart Failure - Business Wire - February 18th, 2024
- Lisa Jarvis: A cure for some kinds of hearing loss? Gene therapies are getting closer - St. Paul Pioneer Press - February 18th, 2024
- Spinal Muscular Atrophy Market: Navigating Therapeutic Advances towards USD 5.6 Billion by 2034, with a CAGR of ... - Yahoo Finance - February 18th, 2024
- Crispr Therapeutics' Gene Therapy Wins EU Approval - TipRanks.com - TipRanks - February 18th, 2024
- Revolutionizing Gene Therapy: A Novel Technique for In Vivo CAR T Cells - Medriva - February 18th, 2024
- How Stella Vnook is 'infusing innovation' into cell therapies with Likarda's technology - BioPharma-Reporter.com - February 18th, 2024
- Using cancer's 'superpower' to boost T-cell therapies in mice - FierceBiotech - February 18th, 2024
- Parkinson's Disease Patient Identification and Education Will Need to Improve When New Disease Modifying ... - Yahoo Finance - February 18th, 2024
- CRISPR (CRSP) to Report Q4 Earnings: What's in the Cards? - Yahoo Finance - February 18th, 2024
- Gene Therapy: A Ray of Hope for Heart Failure Treatment | Health News - Medriva - February 18th, 2024
- Gene therapy trials restore hearing to children born deaf - The Hill - February 2nd, 2024
- Early Trial Success for Inherited Deafness Gene-Therapy - RegMedNet - February 2nd, 2024