More Clinical Data Needed to Develop Novel Therapies for Hearing Loss – Genetic Engineering & Biotechnology News

Over 5% of the world’s population (430 million people) require rehabilitation to address their “disabling” hearing loss, according to the World Health Organization (WHO). The organization predicts that nearly 2.5 billion people worldwide (1 in 4 people) will be living with some degree of hearing loss by 2050, and that at least 700 million will require access to ear and hearing care and other rehabilitation services unless action is taken.

A range of factors may cause or contribute to hearing loss, including noise, diseases, medication, heredity, and aging. While one shared feature across all forms of hearing loss is the lack of approved therapeutic drugs, results from recent animal studies and human clinical trials are encouraging.

“We are working towards an IND submission for our lead product candidate in the first half of 2022,” says Manny Simons, PhD, founder, president, and CEO of Akouos. AK-OTOF, the company’s lead program, uses an adeno-associated viral (AAV) vector-based gene therapy to treat sensorineural hearing loss caused by mutations in the otoferlin gene. Otoferlin, a transmembrane protein, is involved in the calcium-mediated exocytosis of synaptic vesicles in inner hair cells in response to sound, a process that is indispensable for the transmission of electric signals to the brain.

A second Akouos program, AK-anti-VEGF, uses the same AAV vector to deliver a therapeutic protein to treat vestibular schwannoma, a benign tumor with complex etiology that affects about 200,000 people in the United States and Europe and causes significant patient morbidity.

Human clinical studies have reported that VEGF inhibitors can reduce the volume of vestibular schwannoma and hearing. However, one of their major limitations is potential toxicity after systemic administration.

Ear anatomy diagram. [jehsomwang/Getty Images]

“The inner ear is amenable to local delivery and constitutes an ideal site where next-generation genetic medicine modalities can be successful,” says Simons. The human cochlea contains approximately 5,000 inner hair cells, which are the receptors that directly send signals to the central nervous system. “This small target cell population compared to that of other organs allows genetic medicines to be administered at relatively low doses to potentially treat the entire organ and achieve a desired therapeutic effect,” he continues.

Preclinical studies

In preclinical studies, Akouos scientists demonstrated the feasibility of using doses several-fold lower than what is required in other organs, and recently presented data demonstrating tolerability of AK-anti-VEGF administration intracochlearly. The strategy generated robust protein expression levels.

Akouos’ most advanced product candidates leverage the same AAV vector that is delivered to the inner ear and can be adapted to specific products needed for various therapeutic interventions. “This highlights the broad applicability of our platform to address a broad range of inner ear conditions, including much more common disorders with a complex etiology,” says Simons.

A third strategy that …….

Source: https://www.genengnews.com/news/more-clinical-data-needed-to-improve-therapies-for-hearing-loss/