Cell-based Therapies for Hearing and Balance Disorders
Dr. Xue Zhong Liu was awarded an R01 research grant to develop human, inner-ear organoid platforms to study hearing and balance disorders.
The National Institutes of Health (NIH) awarded Xue Zhong Liu, M.D., Ph.D., the Leonard M. Miller Professor and vice chair of research in the Department of Otolaryngology-Head and Neck Surgery at the University of Miami Miller School of Medicine, a five-year, $4 million R01 research grant to develop human, inner-ear organoid platforms for human hearing and balance disorders, work that will be primarily conducted at Dr. Liu’s lab in the Miller School’s Interdisciplinary Stem Cell Institute (ISCI).
A Widespread Problem without a Cure
Congenital or acquired hearing loss affects approximately 30 million people in the United States alone. Genetic causes are common, with more than 200 genes causing hearing loss in humans. There is no cure.
“Today’s treatment for hearing loss is limited to cochlear implants or hearing aids, but there is no biological treatment for hearing loss,” said Dr. Liu, the Marian and Walter Hotchkiss Endowed Chair in Otolaryngology and professor of otolaryngology, human genetics, biochemistry and pediatrics at the Miller School. “There is an unmet need to develop alternative treatment options.”
The NIH grant will fund Miller School research to generate human, inner-ear organoids (hIEOs) from patient pluripotent stem cells (hiPSCs) as a model system to test inner-ear gene therapies. The study looks to introduce advanced genome editing strategies to silence dominant mutations or repair recessive mutations that cause dysfunction in human sensory hair cells.
The grant research aims to establish a new paradigm for personalized genetic models of hIEOs affected in hearing loss. Dr. Liu’s work will involve in vitro screening of available therapeutics and multi-omic identification of disease and biomarkers for treatment responses.
“Our aim is to lay the foundation for moving cell therapy approaches closer to clinical trials on humans with hearing loss,” said Dr. Liu.
After establishing a human ear tissue repository at the University of Miami Ear Institute, Dr. Liu’s team will use iPSCs to grow tiny, three-dimensional structures that resemble the inner ear. These organoids allow scientists to study organ development and offer new possibilities for replacing damaged tissue lost to hearing and balance disorders. Dr. Liu’s team has developed the organoids from patients with genetic hearing and balance issues, allowing the researchers to study the inner ear in early and late stages of development.
A Shift in Therapeutic Development
Although still experimental, Dr. Liu said stem cell-based therapies will be a major shift in therapeutic development within the next five to 10 years. Doctors in the United States will be able to prescribe stem-cell based therapies for a variety of health conditions and move away from treating disease by addressing single defects, according to Joshua Hare, M.D., Louis Lemberg Professor of Medicine in the Division of Cardiovascular Medicine and director of the ISCI at the Miller School.
“Recent breakthroughs in genetic screening, gene or cell-based therapeutics and gene editing for the inner ear can lead to novel therapies for multiple classes of hereditary hearing loss,” said Dr. Hare, who is also director of the Donald Soffer Endowed Program in Regenerative Medicine and chief science officer at the Miller School. “We are excited about this special NIH grant.”
“This cell therapy grant was awarded because the work is considered high impact and helps to meet an unmet patient need,” 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 genetic hearing loss clinic at the UM Ear Institute is a multidisciplinary program that provides diagnostic and molecular testing, genetic counseling and intervention options for patients who are dealing with various types of hearing loss.
Co-investigators of the grant include:
• Derek Dykxhoorn, Ph.D., research associate professor in the Dr. John T. Macdonald Foundation Department of Human Genetics
• Anthony Griswold, Ph.D., assistant professor in the John P. Hussman Institute for Human Genomics
• Ashutosh Agarwal, Ph.D., from the University of Miami Department of Biomedical Engineering
• Pei-Ciao Tang, Ph.D., and Denise Yan, Ph.D., both researchers in the Miller School’s Department of Otolaryngology.
Tags: Dr. Anthony Griswold, Dr. Ashutosh Agarwal, Dr. Denise Yan, Dr. Derek Dykxhoorn, Dr. Pei-Ciao Tang, Dr. Xue Zhong Liu, genetics, genome editing, hearing loss, otolaryngology, stem cell therapies, University of Miami Ear Institute