With promising early results, cell and gene therapies are making headway against both rare and common ocular and auditory diseases.
Eyes and ears. Two of our most critical sensory organs yet usually taken for granted—until something goes wrong. But while largely ignored by busy individuals and most insurance plans, biopharma R&D—specifically cell and gene therapy—is paying attention.
Let’s start with hearing. The human ear is made up of three different parts: the outer ear, middle ear and inner ear—a complex structure offering many opportunities for something to go wrong.
Hearing Loss Breakthroughs
This spring, Regeneron made headlines when it announced that the investigational gene therapy DB-OTO improved hearing in two young children with “profound genetic deafness” since birth, with one patient returning to normal hearing levels within six months of treatment. In this case, the children’s hearing loss was due to a deficiency in otoferlin, a protein expressed in the hair cells of the inner ear. Regeneron’s gene therapy delivers a functioning copy of the gene to the inner ear, stimulating otoferlin production.
Eli Lilly subsidiary Akouos and Fudan University in Shanghai and Mass Eye and Ear have also enjoyed early success with otoferlin gene therapies. Of course, these therapies will only help the 1% to 8% of patients afflicted by this particular genetic mutation. However, according to the American Hearing Research Foundation, about 75% of congenital deafness has a genetic cause, indicating the potential for more gene therapies.
Although I can hear perfectly well, hearing loss is a condition with which I am quite familiar. My grandfather was born deaf. He never knew the cause but, today, he could have had his DNA tested and had the hope of a treatment on the horizon.
Ocular CGT Advances
On the ocular side, cell and gene therapies are making progress against more common diseases like wet age-related macular degeneration (AMD), a leading cause of blindness, as well as dry eye syndrome (DED)—and here my interest is even more personal. Four years ago, I began to experience a scratchy, gritty sensation in my eyes. This quickly graduated to a burning, sandpaper-dry condition that makes everyday tasks—like driving a car or staring at a computer screen—challenging. I’m far from the only one dealing with these issues. I’ve commiserated with at least two colleagues, which isn’t surprising as DED affects around one in 11 people worldwide, according to the NIH.
After exhausting the first tier of treatments—such as prescription eye drops, omega-3 fatty acids, intense pulsed light therapy and scleral contact lenses—I learned about a cellular therapy called amniotic membrane treatment. Extracted from the innermost layer of the human placenta, amniotic membrane is full of neurotrophic factors such as nerve growth factor, collagen and basal epithelial cells. It also contains unique anti-inflammatory, anti-fibrotic and pro-healing properties that can help ease conditions like DED, corneal neuropathic pain, graft versus host disease and post-corneal transplants, according to an article published in Ocular Surface.
A 2018 study found that 74 of 84 patients enjoyed an improved ocular surface and a “notable” reduction in symptom severity after just over a week of treatment with amniotic membrane. As with many therapies, it doesn’t always work the first time; 10% of eyes in this study required repeated treatment, and I personally am on my second round. Interestingly, this study breaks the data down by individual eyes, as patients did not always have the same response in both eyes. I have so far experienced slightly better results in my right eye from this second round of treatment.
Companies are also making progress on the gene therapy side, specifically for wet AMD. REGENXBIO and AbbVie, Adverum and 4D Molecular Therapeutics have all seen positive results from their investigative gene therapies for this condition, which affects around 1.5 million people in the U.S. alone—a far bigger patient population than current rare disease gene therapies target.
The mechanism for these wet AMD treatments is also different from traditional gene therapies, which work by repairing or replacing a faulty disease-causing gene. For wet AMD, investigational gene therapies deliver the coding sequence for the therapeutic molecule to the eye, which serves as a biofactory to produce the medicine. This could ease the treatment burden of the multiple injections currently required to treat the disease.
Several other companies, including AbbVie and Capsida Biotherapeutics, Kriya Therapeutics and SpliceBio, are developing gene therapies to treat thyroid eye disease, inherited retinal disease and more.
Having been treated with one of these therapies, I can also attest to the fact that they are not cheap. But progress is being made. While gene therapies for rare diseases that correct or replace a faulty gene can carry a multi-million-dollar price tag, experts say the cost of the wet AMD treatments currently in development will be much lower. There is definitely a ray of light and a joyful noise on the horizon.
