August 8, 2022
Delivering the protein EPS8 via gene therapy rescues malfunctioning inner ear hair cells that transduce sound
LA JOLLAScientists from the Salk Institute and the University of Sheffield co-led a study that shows promise for the development of gene therapies to repair hearing loss. In developed countries, roughly 80 percent of deafness cases that occur before a child learns to speak are due to genetic factors. One of these genetic components leads to the absence of the protein EPS8, which coincides with improper development of sensory hair cells in the inner ear. These cells normally have long hair-like structures, called stereocilia, that transduce sound into electrical signals that can be perceived by the brain. In the absence of EPS8, the stereocilia are too short to function, leading to deafness.
The teams findings, published in Molecular Therapy Methods & Clinical Development online on July 31, 2022, show that delivery of normal EPS8 can rescue stereocilia elongation and the function of auditory hair cells in the ears of mice affected by the loss of EPS8.
Our discovery shows that hair cell function can be restored in certain cells, says co-senior author Uri Manor, assistant research professor and director of the Waitt Advanced Biophotonics Core at Salk. I was born with severe to profound hearing loss and feel it would be a wonderful gift to be able to provide people with the option to have hearing.
The cochlea, a spiral tube structure in the inner ear, enables us to hear and distinguish different sound frequencies. Low-frequency regions of the cochlea have longer stereocilia while high-frequency regions have shorter stereocilia. When sound travels through the ear, fluid in the cochlea vibrates, causing the hair cell stereocilia to vibrate. These hair cells send signals to neurons, which pass on information about the sounds to the brain.
Manor previously discovered that the EPS8 protein is essential for normal hearing function because it regulates the length of hair cell stereocilia. Without EPS8, the hairs are very short. Concurrently, co-senior author Walter Marcotti, professor at the University of Sheffield, discovered that in the absence of EPS8 the hair cells also do not develop properly.
For this study, Manor and Marcotti joined forces to see if adding EPS8 to stereocilia hair cells could restore their function to ultimately improve hearing in mice. Using a virus to help deliver the protein to hair cells, the team introduced EPS8 into the inner ears of deaf mice who lacked EPS8. They then used detailed imaging to characterize and measure the hair cell stereocilia.
The team found that EPS8 increased the length of the stereocilia and restored hair cell function in low-frequency cells. They also found that after a certain age, the cells seemed to lose their ability to be rescued by this gene therapy.
EPS8 is a protein with many different functions, and we still have a lot more to uncover about it, says Manor. I am committed to continuing to study hearing loss and am optimistic that our work can help lead to gene therapies that restore hearing.
Future research will include looking at how well EPS8 gene therapy might work to restore hearing during different developmental stages, and whether it might be possible to lengthen the therapeutic window of opportunity.
Other authors on the study are Colbie Chinowsky, Tsung-Chang Sung and Yelena Dayn of Salk; Jing-Yi Jeng, Adam Carlton, Federico Ceriani and Stuart Johnson of the University of Sheffield; Richard Goodyear and Guy Richardson of the University of Sussex; and Steve Brown and Michael Bowl of the MRC Harwell Institute.
The research was supported by the Biotechnology and Biological Sciences Research Council (BB/S006257/1, BB/T016337/1), Waitt Foundation, Grohne Foundation, National Institutes of Health (CA014195, R21DC018237), National Science Foundation (NeuroNex Award 2014862), Chan-Zuckerberg Initiative (Imaging Scientist Award) and Dudley and Geoffrey Cox Charitable Trust.
DOI: 10.1016/j.omtm.2022.07.012
More here:
Discovery advances the potential of gene therapy to restore hearing loss - Salk Institute
- 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
- Sickle cell gene therapy first focus of Medicaid pay model - Modern Healthcare - February 2nd, 2024
- Beyond chemotherapy: Navigating the promise and perils of CAR-T therapy in pediatric cancer - BioPharma-Reporter.com - February 2nd, 2024
- Angiodema: Gene therapy blocks painful hereditary disorder - BBC - February 2nd, 2024
- FDA: Genome editing therapies may use accelerated approval pathway - Regulatory Focus - February 2nd, 2024
- CRISPR tech treats severe hereditary condition successfully - Interesting Engineering - February 2nd, 2024
- Gene Therapy Restores Hearing in Small Trial for Kids With Hereditary Deafness - Technology Networks - February 2nd, 2024
- Gene-based therapy may slow development of life-threatening heart condition - Medical Xpress - February 2nd, 2024
- Jaguar Gene Therapy Announces FDA Clearance of IND to Study JAG201 in a Genetic Form of Autism Spectrum ... - Business Wire - February 2nd, 2024
- Replacing the PKP2 gene prolongs survival in ARVC patients - Drug Target Review - February 2nd, 2024
- Cell and gene therapies top pharmaceutical industry trend to watch for 2024 - Pharmaceutical Technology - February 2nd, 2024
- Gene Therapy Restores Hearing in Children with Hereditary Deafness - The Hearing Review - February 2nd, 2024
- 2 Dutch among 10 "functionally cured" of hereditary swelling disease by new gene therapy - NL Times - February 2nd, 2024
- FDA publishes final industry guidance for CAR-T and gene therapies - PMLiVE - February 2nd, 2024
- Gene therapy cures hereditary deafness in two people - Advanced Science News - February 2nd, 2024
- Hearing Restored in Deaf Children in Gene Therapy Clinical Trial - Securities.io - February 2nd, 2024
- Vivet Therapeutics Receive 4.9 Million to Advance Development of Gene Therapy - European Pharmaceutical Manufacturer - February 2nd, 2024
- Adverum Biotechnologies will Host Webcast to Review LUNA Phase 2 Preliminary Efficacy and Safety Results on ... - GlobeNewswire - February 2nd, 2024
- Allogene parks Notch CARs, leaving one on the road - FierceBiotech - February 2nd, 2024
- Experimental gene therapy allows kids with inherited deafness to hear - The Associated Press - January 25th, 2024