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| Hemant Khanna, Ph.D., John Heckenlively, M.D., David Zacks, M.D., Ph.D., (standing) and Naheed Khan, Ph.D., Debra Thompson, Ph.D., (seated) are on the Michigan team studying retinitis pigmentosa. |
Consortium Seeks
Answers on RP
Is there more than one way to rescue a photoreceptor?
Scientists and physicians from three universities are teaming up to develop therapies for an inherited retinal degenerative eye disease. Funded by the Foundation Fighting Blindness (FFB), the project brings together the best minds from various disciplines and perspectives to collaborate on treatments for X-linked retinitis pigmentosa (XLRP). A patient with XLRP has generously underwritten the research. Together the team will explore a variety of therapeutic approaches, all intended to replace or rescue dying photoreceptors.
Of the seven team members, five are from the U-M Kellogg Eye Center. Collaboration is becoming an increasingly favored approach in research, says Debra A. Thompson, Ph.D., who will direct one section of the study. She points to recent results of a small study in which patients regained some vision after receiving gene therapy for a degenerative eye disease. “With this stunning success for patients with the RPE65 mutation, we now have evidence that similar approaches could work for a larger group of patients whose vision is compromised by other genetic mutations.”
Retinitis pigmentosa is a group of diseases that cause slow but progressive loss of vision usually over decades. The designation “X-linked” means that the mutation responsible for the disease is carried on the X chromosome. Simply stated, this disorder results in the loss of photoreceptors, the rods and cones responsible for vision. Scientists who make up the FFB Consortium will explore different strategies for restoring the function of photoreceptors and preventing their loss.
The project initially centers on a mouse model of XLRP identified by Kellogg’s John R. Heckenlively, M.D., in collaboration with the Jackson Laboratory. The model, known as rd9, has the same gene and type of mutations as seen in humans with XLRP.
Using this mouse model, Hemant Khanna, Ph.D., and David N. Zacks, M.D., Ph.D., will explore whether cell-replacement therapy is an effective strategy for restoring lost vision. They will transplant healthy photoreceptor rods into the retinas of the diseased mice, with the goal of achieving at least partial recovery of the rods’ ability to function. This builds on the work of Anand Swaroop, Ph.D., now a senior scientist at the National Eye Institute, whose work at Kellogg led to successful transplantation of rod precursor cells into blind mice in 2006. Dr. Swaroop, whose lab identified a key mutation in the RPGR gene, was the driving force behind the creation of the Consortium.
Taking another tack, researchers at the University of Pennsylvania and the University of Florida will seek to repair photoreceptor damage by delivering therapeutic or “healthy” forms of the RPGR gene into the retina. They will investigate strategies using modified viruses that act as vectors to carry a replacement copy of the affected gene. The replacement genetic material was constructed at Kellogg by Dr. Khanna’s laboratory.
While gene delivery using viral vectors has been successful in treating certain degenerative eye diseases, Kellogg’s Dr. Thompson observes that there are still lingering concerns about the safety of the approach. She is exploring alternate methods, involving the delivery into the eye of small molecules expected to rescue failing photoreceptor physiology affected by the RPGR mutation.
Dr. Heckenlively, who sees patients with a range of inherited retinal diseases, and whose project found over 100 mouse models of human eye disease, will evaluate the effectiveness of each approach. Dr. Heckenlively will review fundus photographs and ERG recordings to see how close each approach has come to the collective goal of rescuing photoreceptors.
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