Modern medicine can feel like a bit of magic

Lisa Jarvis, Tribune News Service

Every once in a while, modern medicine can feel like a bit of magic. Like when a vaccine is shown to eliminate cases of cervical cancer among young women or gene editing allows someone with sickle cell disease to live without constant pain. Or when an experimental gene therapy allows a deaf 11-year-old boy to hear. Aissam Dam is now able to hear sound for the first time in his young life. The treatment he received, developed by Eli Lilly & Co. subsidiary Akouos Inc., is aimed at fixing the underlying cause of his congenital deafness. As someone who has followed this field for many years, watching drug after drug for various types of hearing loss fail, reading about Dam’s experience gave me goosebumps. Finally, some momentum.

Until now, the options for addressing hearing loss have been limited to devices — a hearing aid can amplify sound for people whose ears can still detect and transmit it, whereas a cochlear implant bypasses damaged parts of the ear to stimulate the auditory nerve. The current advance can’t help the millions of people in the US experiencing some level of hearing loss — or even most of the people with common forms of congenital deafness. But the path to treatments suddenly looks clearer. “It’s very exciting,” says Nancy Young, who founded the Lurie Children’s Cochlear Implant program. “It’s the beginning of the future.” “Beginning” is an important word for families wondering if this treatment or another like it could someday be available to their children with congenital deafness. It’s very early days, and there are some caveats to consider.

The first is that Dam had a very rare form of congenital hearing loss. The gene therapy corrects a mutation that prevents cells in the ear from making a functional form of a protein called otoferlin, variants of which are found in just 1%-8% of infants born without the ability to hear. People with this form of hearing loss have all the right architecture in their ear. Their cochlea is fully formed and all the thousands of sensory cells that line it, called hair cells, are intact. Those hair cells just can’t send a signal to the brain. That differs from most other forms of genetic deafness, in which those hair cells die off, sometimes as early as in the womb. That’s a much harder problem to fix because we don’t make new hair cells — what we’re born with is all we’ve got. Damage to those cells is the main reason why hearing loss is so common as we age. (Let this serve as your reminder to turn down the volume on your headphones and carry earplugs to your next concert.) A gene therapy for more common forms of congenital hearing loss — or really most kinds of hearing loss — likely will need to coax the body into making new hair cells. That’s a tall order, and the one prominent attempt to do so, a gene therapy developed by Novartis and tested in adults, did not pan out.

But there’s also reason to think that what is being learned from efforts to treat otoferlin-mediated hearing loss could inform the development of more complex treatments. While the biology of each form of congenital hearing loss is unique, the way the therapies are delivered is a critical part of inventing other drugs, says Emmanuel Simons, chief executive officer of Akouos and senior vice president of gene therapy at Lilly. That might not sound like a big deal, but a chronic challenge for all gene therapies is delivering enough of the genetic material to the right cells. In Dam’s case, doctors at the Children’s Hospital of Philadelphia used a special procedure to drip a relatively modest dose of the therapy — a type of hollowed-out virus stuffed with many copies of the genetic fix — directly into his inner ear. That represents significant progress. Lilly isn’t the only one making progress, either. Researchers from the Eye & ENT Hospital of Fudan University and Shanghai-based Refreshgene Therapeutics said they’d developed a similar gene therapy that restored hearing in 5 of 6 children. The kids who enrolled in the small study, published recently in The Lancet, ranged from 1 to 6 years old. Four of them had a cochlear implant in one year.