A long list of retinal dystrophies, including retinitis pigmentosa, Stargardt disease, Leber congenital amaurosis (LCA), achromatosopia, X-linked retinoschisis, Usher syndrome and choroideremia, can be traced to inherited changes in DNA. All of these conditions lead to progressive vision loss; some end in total blindness.
Until very recently, these wide-ranging disorders shared one thing in common: there were no available treatments for them.
Today, advances in gene therapy are finally yielding new options that may revolutionize the treatment of inherited retinal degenerations, giving retinal specialists new tools and patients and families new hope.
Retinal cells in inherited retinal disorders do not function normally due to a gene defect. In gene replacement therapy, a working copy of a gene is embedded in a virus that is injected into the vitreous or under the retina. The virus delivers the correct DNA to the affected retinal cells.
While the majority of gene therapy options are still in experimental trials to confirm their safety, efficacy, and dosing, the FDA has approved one gene therapy, Luxturna™ (voretigene neparvovec-rzyl) to correct a defect in the gene RPE65 that leads to Leber Congenital Amaurosis.
In fact, Luxturna™ is the only FDA-approved gene replacement therapy for any human disease linked to a genetic change. Kellogg is one of ten treatment centers in the country approved to offer the treatment, and Dr. Cagri Besirli, MD, PhD, anticipates that patients at Kellogg will receive injections soon.
Gene therapy is anything but simple; it takes an extraordinary team effort to get these treatments to the patients who need them. Kellogg is one of the few centers in the U.S. with the multidisciplinary expertise to offer this new generation of gene therapy clinical trials for other conditions.
Kellogg’s team of retinal specialists devoted to the diagnosis and management of patients with inherited retinal disorders includes Cagri Besirli, MD, PhD, Abigail Fahim, MD, PhD, and K. Thiran Jayasundera, MD, FACS. Dr. Besirli, a pediatric retinal surgeon, serves as principal investigator of several ongoing therapeutic trials. “Ultimately, we want these therapies to be available for our youngest patients,” he explains. “The sooner they receive treatment, the less vision loss they may have to endure.”
Dr. Jayasundera is the principal investigator on research that precedes clinical testing, called natural history studies (NH). “NH studies collect and analyze patient information to draw a clearer picture of how these disorders develop and progress,” he explains. “NH is especially important for designing clinical trials of new treatments for these diseases.”
Other critical members of the team include Kellogg electrophysiologists, led by Naheed Khan, PhD, whose work guides both diagnosis and treatment; genetic counselors Kari Branham, MS, CGC, and Dana Schlegel, MS, MPH, CGC, who help families navigate the complexities of their disease; Adrienne Chen, PhD; and the staff of the Kellogg Clinical Research Center (KCRC). Branham and Schlegel are two of only about 50 genetic counselors in the world dedicated solely to ophthalmology. Kellogg is also fortunate to work with Professor Robin Ali, of the University College of London, and his team on these efforts.
Kellogg is currently conducting gene therapy clinical trials and natural history studies for a range of inherited retinal conditions. Dr. Besirli is excited to be part of the group bringing gene therapy to patients at Kellogg. “For so long, we’ve struggled to help patients facing these blinding illnesses,” he says. “Gene therapy is still in its infancy, but there is reason for optimism. We have an FDA-approved treatment for one condition and numerous promising options for others. We have an outstanding retinal dystrophy team, and we have amazing patients. It’s a very exciting time.”