Therapeutic Pipeline for Retinal Dystrophies

The Advanced Therapy Program is developing a multi-pronged approach to the development of new therapies for retinal degeneration. We are drawing on the expertise and leadership of researchers and physicians at the Kellogg Eye Center to achieve our aim of leveraging cutting-edge research and technology for the treatment of eye disease.

Gene therapy to treat inherited retinal dystrophy

Recent pioneering work by Robin Ali, Ph.D., a Visiting Professor at the Kellogg Eye Center from University College London Institute of Ophthalmology and Moorfields Eye Hospital, has demonstrated the promise of gene therapy for inherited retinal dystrophies. Defects in the RPE65 gene lead to a form of Leber congenital amaurosis (LCA), a severe, early-onset retinal degeneration that eventually results in blindness. In clinical trials, Dr. Ali and others have demonstrated improved vision in these patients following gene therapy. Dr. Ali is working with John Heckenlively, M.D., Debra Thompson, Ph.D., and others at the Kellogg Eye Center to build a gene therapy program to treat a number of retinal disorders. This includes pre-clinical studies in animal models, on through the initiation of clinical trials. Dr. Ali is working with Dr. Thompson to develop a gene therapy treatment for patients with a form of LCA caused by defects in the RDH12 gene. They are currently determining whether gene therapy is effective in a mouse model of this disease, which is an essential step before testing the therapy in patients. There are also plans to initiate other clinical trials, including a trial of a new improved gene therapy for LCA caused by defects in RPE65.

Stem cell therapy to treat retinal dystrophy

Once the cells in the retina die and are lost, they are not replaced since the cells in the retina do not regenerate. The aim of stem cell-based therapies is to restore visual function by replacing the missing cells. Robin Ali, Ph.D., has recently shown that embryonic stem cells can be used to generate photoreceptors that can then be successfully transplanted into adult mouse retinas. This provides the basis for pursuing a similar strategy using human stem cell-derived photoreceptors to replace cells that have been lost in patients. Sally Temple, Ph.D., and Jeffery Stern, M.D., Ph.D., have also recently shown that a subset of adult retinal pigment epithelial (RPE) cells can be induced to become RPE stem cells that can proliferate and re-differentiate, providing an accessible multipotent stem cell. Together with Rajesh Rao, M.D., who studies the role of epigenetics in re-programming stem cells, these scientists at the Kellogg Eye Center are developing a program for pre-clinical and clinical studies of stem cell-derived RPE and photoreceptor transplantation for the treatment of advanced retinal disease.

Retinal prosthesis implants to improve visual function

Thiran Jayasundera, M.D., and David Zacks, M.D., Ph.D., at the Kellogg Eye Center have performed the first four surgeries in the United States to implant the FDA approved Argus II Retinal Prosthesis (or “bionic eye”). The Kellogg Eye Center is one of 12 Centers of Excellence in the country to offer this artificial retina, which is intended for treatment of patients with late stage retinitis pigmentosa. Patients implanted with this retina have exhibited improved visual function, despite their disease having progressed to the point of having “bare light” or no light perception in both eyes.

Press Release:

Novel drugs for treating retinitis pigmentosa

  • Valproic acid for treating retinitis pigmentosa

    The Kellogg Eye Center, under the direction of John Heckenlively, M.D., and Thiran Jayasundera, M.D., is participating in a multi-center Phase II clinical trial to evaluate the efficacy of using valproic acid for treatment of autosomal dominant retinitis pigmentosa (RP). RP is a severe disease of the retina that begins with night blindness and tunnel vision and eventually leads to the loss of central vision and total blindness; there is currently no FDA-approved therapy that either significantly alters or reverses the progression of RP. Valproic acid has been approved by the FDA for the treatment of epilepsy, and is also a good candidate for treatment of RP.

    Information about the Trial of Oral Valproic Acid for Retinitis Pigmentosa (VPA):

  • Small molecule inhibitors of photoreceptor cell death

    Death of photoreceptor cells in the eye is a major cause of vision loss. The photoreceptors detect light and transmit signals to the brain, and degeneration of these cells occurs during numerous ocular disorders ranging from retinal dystrophies to retinal detachment. David Zacks, M.D., Ph.D., has recently identified a small molecule inhibitor that prevents photoreceptor cell death during retinal detachment, and is developing a therapeutic to reduce the vision loss that can occur following retinal detachment and reattachment surgery. This neuroprotective therapy could also benefit patients with many other forms of retinal degeneration where photoreceptors are lost, such as retinitis pigmentosa, diabetic retinopathy, and age-related macular degeneration.

Advanced diagnostic tools

Our leading-edge research employs advanced tools to evaluate visual function, and sophisticated genetic testing to diagnose patients and further characterize the genetic bases of inherited retinal dystrophies. Naheed Khan, Ph.D., at the Kellogg Eye Center uses retinal electrophysiology to study animal models of human eye disease to develop improved objective measures for visual function, and Kari Branham, M.S., C.G.C., provides genetic counseling for patients associated with multiple studies at the Kellogg Eye Center.

Diagnostic Visual Electrophysiology Service:

Last Modified: Monday, 18-Aug-2014 15:14:36 EDT