Could gene therapy restore lost hearing?

Adult-onset hearing loss affects one-third of adults over the age of 60. As with hearing loss at any age, this form of progressive deafness can lead to social isolation, depression, decreased economic and educational success, and cognitive decline.

Each year, tens of thousands of adults with hearing loss obtain hearing aids, and thousands more undergo cochlear implantation. For most, the cause of their hearing loss remains undetermined, leaving providers with limited therapeutic options. The Penn Center for Adult-Onset Hearing Loss, the first of its kind in the United States, aims to change this by better understanding the genetics of the condition and developing treatment options for adult-onset hearing loss.

A collaborative initiative between Penn’s Departments of Otorhinolaryngology and Genetics, the center seeks to expand genetic testing for the underserved adult hearing loss population. Co-led by Douglas J. Epstein, PhD, and Tiffany Peng Hwa, MD, the center is dedicated to advancing the understanding and treatment of adult hearing loss. Despite significant progress in pediatric hearing loss, including the successful use of gene therapy at Children’s Hospital of Philadelphia to treat a rare pediatric form of hearing loss, adult-onset hearing loss remains less understood.

Launching a wide-reaching, collaborative effort to improve options for adults with hearing loss begins by better understanding the underlying genetics, which requires a wealth of genomic and clinical data. Penn Medicine’s electronic health record and BioBank—an integrated, centralized resource for consenting, collecting, processing, and storing DNA, plasma/serum, and tissue for human genetics and translational research—give the Center for Adult-Onset Hearing Loss an advantage in identifying patterns and genetic variants. Armed with the right resources, Penn’s team is uniquely positioned to gain critical insights into the origins of adult-onset hearing loss.

Few people undergo genetic testing for hearing loss even when a genetic cause is suspected from family history. For the 80 percent of people with hearing loss who are diagnosed after the second decade of life, this leaves an important question unasked.

Patients at Penn Medicine's Center for Adult-Onset Hearing Loss have the option of undergoing genetic testing to understand whether they have genetic variants associated with hearing loss.

For patients, this information may help clarify the diagnosis of a genetic syndrome and guide or adjust their medical care; provide information about prognosis; and inform family members about their own potential risk of developing hearing loss.

Through this process, the center may also be able to identify novel genetic variants associated with hearing loss, which could help in the diagnosis of future patients. This data will contribute to the creation of new genetic hearing loss treatments to prevent and potentially cure the condition.

Impact philanthropy

Philanthropic support has been integral to the early success of the Center for Adult-Onset Hearing Loss and is essential for its continued growth and sustainability, including the launch of initiatives that will accelerate its impact. This includes support from the Clara E. and John H. Ware, Jr. Foundation, which has provided over $1 million since the Center’s inception to support basic and clinical research, including early research to develop a gene therapy for an adult form of hearing loss. Most recently, the team’s work was bolstered by a new partnership with M. Kort Schnabel (a 1998 Penn alumnus) and Kathryn Schnabel, whose generous $1 million gift to establish the Schnabel Family Hearing Loss Research Fund has enabled the development and launch of the Hearing Loss Clinical Research Data Platform.

The establishment of the Hearing Loss Clinical Research Data Platform is a crucial next step in achieving the center’s mission of exploring the role of genetics in adult-onset hearing loss. As the team continues to gather data from a critical mass of individuals with hearing loss, the platform will serve as a centerpiece of the clinical program and meet a significant research need: a publicly available, searchable database that will accelerate research and enhance patient care, linking audiometric and demographic data from the electronic health record with genetic data in the Penn Medicine BioBank. This accessible database will enable researchers to analyze data, clinicians to better understand patients with genetic forms of hearing loss, patients to know more about the genetics underlying their conditions, and family members to better understand their genetic risk.

“We do not know enough about the genetic architecture of hearing loss in adults,” said Epstein, Center for Adult-Onset Hearing Loss co-director and vice chair and professor of Genetics. “This exciting new data platform will change that. Now, our talented and multidisciplinary team at Penn will be able to leverage a wealth of data to build a better understanding of the genetics of hearing loss. Even more, we can extend this valuable resource to scientists around the world, accelerating collaborative efforts and ultimately improving outcomes for patients. We are so grateful to the Schnabels for their support, which makes this possible.”

Hwa, also co-director of the center and an assistant professor of Otorhinolaryngology-Head and Neck Surgery, said, “The Hearing Loss Clinical Research Data Platform has the potential to change how we address adult-onset hearing loss. Thanks to the Schnabels’ gift, this robust and widely accessible database will foster new discoveries and collaboration, and the knowledge gained will help clinicians and patients make better treatment decisions.”

Kort Schnabel, who received his bachelor’s degree in economics from Penn, is CEO of Ares Capital Corporation. He is the grandson of the late Truman G. “Nipper” Schnabel Jr., MD, a renowned Penn physician who helped establish the first cardiac catheterization unit at the Hospital of the University of Pennsylvania and later served as acting director of Penn’s program in geriatric medicine and of the Institute on Aging. Kort’s great-grandfather and Nipper’s father, Truman Schnabel Sr., MD, was also a professor in the School of Medicine.

“Kathryn and I are thrilled to help advance hearing loss research and to help Penn remain at the forefront of this important field of study,” said Kort Schnabel. “Hearing loss is a debilitating but often misunderstood condition, and we hope researchers, caregivers, and patients will all benefit from Penn’s new data platform for many years to come.”

To learn more about the Center for Adult-Onset Hearing Loss, visit the Center website; to make an appointment, please call 215-662-2784 or email CAOHL@pennmedicine.upenn.edu.

To support the Center for Adult-Onset Hearing Loss, visit the Center’s giving page.