Using Somatic Cell Genome Editing to Investigate Treatments for Hearing Loss
Article Summary
- Xue Zhong Liu, M.D., Ph.D., is a principal investigator on a $16 million NIH somatic cell genome editing grant.
- The grant focuses on investigational new drug (IND)-enabling studies for platform clinical trials of genome editing in multiple diseases.
- The research explores using adeno-associated virus (AAV)-mediated editing to treat human autosomal dominant hearing loss.
The University of Miami Miller School of Medicine’s Xue Zhong Liu, M.D., Ph.D., the Leonard M. Miller Professor and vice chairman of research in the Department of Otolaryngology-Head and Neck Surgery, is one of the principal investigators on a $16 million National Institutes of Health (NIH) somatic cell genome editing grant.
The grant focuses on investigational new drug (IND)-enabling studies for platform clinical trials of genome editing in multiple diseases.
Speeding Up the Editing Therapy Regulatory Path
The research, which explores using adeno-associated virus (AAV)-mediated editing to treat human autosomal dominant hearing loss, follows up on an earlier study by Miller School investigators which showed mutations in both genes for human autosomal dominant deafness-41 (DFNA41) and deafness nonsyndromic autosomal dominant 2 (DFNA2) hearing loss in human and animal models.
Research teams will conduct an IND-enabling study to treat DFNA41 due to a mutation in the P2RX2 gene and DFNA2 due to a mutation in the KCNQ4 gene. The goal is to develop a single, streamlined regulatory process approved by the FDA using the same delivery vehicle, editor and delivery route, with two guide RNAs (gRNAs) to target two types of hearing loss.
The study may open the door to speeding up the development of clinical editing therapy for adult progressive hearing loss. The researchers hope to streamline the regulatory path for editing therapy for genetic hearing loss and initiate two clinical trials subsequently.
Progressive Hearing Loss
In DFNA41, hearing loss begins at high frequencies between ages 15 and 25 and gradually affects other frequencies. Initially mild or moderate, hearing loss progresses to severe or profound over time. Patients with DFNA41 are also highly susceptible to noise-induced hearing loss.
In DFNA2, hearing loss begins within the first two years of life, starting at high frequencies and then getting worse across other frequencies. Hearing loss also progresses from mild or moderate to severe or profound. Treatment typically involves hearing aids or cochlear implants, depending on severity.
“The ultimate goal is to be able to develop treatments for as many patients as possible,” said Dr. Liu, also the Marian and Walter Hotchkiss Endowed Chair in Otolaryngology. “Longer term, we believe similar approaches can be used to restore hearing loss caused by aging or other noise damage.”
“Dr. Liu and the collaborative team’s work is truly transformative, with pioneering preclinical discovery research at the UHealth Ear Institute leading to this IND-enabling study aimed at reversing common forms of human, genetic hearing loss,” said Fred Telischi M.D., M.E.E., FACS, the James R. Chandler Chairman of the Department of Otolaryngology-Head and Neck Surgery and professor of otolaryngology, neurological surgery and biomedical engineering at the Miller School.
The research will be a collaborative effort with scientists from five institutions, including the Miller School:
• Zheng-Yi Chen, DPhil, the grant principal investigator and an associate professor of otolaryngology–head and neck surgery at Harvard Medical School
• Roger Hajjar, M.D., the director of the MGB Gene and Cell Therapy Institute at Mass General Brigham
• Yilai Shu, M.D., Ph.D., professor and director of the Diagnosis and Treatment Center of Genetic Hearing Loss in Shanghai
• Ben Kleinstiver, Ph.D., an associate professor of pathology at Harvard Medical School
Tags: Department of Otolaryngology, Dr. Xue Zhong Liu, gene editing, hearing loss, otolaryngology