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Gene therapy of an immune signaling strategy may propose a mutation-independent approach to preserve vision in RP

Researchers in the Department of Genetics, Harvard Medical School, Boston, US, have published a study on a mutation-independent strategy for the treatment of cone cell photoreceptors in retinitis pigmentosa (RP). RP has an incidence of about 1 in 4,000 people worldwide and the cause of the disease can arise in over 80 different genes with many of these genes having multiple mutations. As a result, it is very unlikely to be able to build each treatment for each cause. To overcome this problem, reseachers in Harvard have developed a gene therapy study to use a small secreted protein treatment to rescue cone photoreceptors cells in the retina. While rod photoreceptor cells deteriorate over time and lead to cone cell death, the current rescue here appears to obtain long-term cone cell survival in RP animal models.  An AAV (adeno-associated virus) that incorporates a gene for a chemokine (fractalkine) has now shown to prolong cone cells in three different forms of RP and this study may provide a potential treatment for this disease, subject to clinical trials.


A chemokine is one type of a gene called “CX3CL1” and this codes for a 373-amino acid protein with a single transmembrane domain that can undergo proteolytic cleavage to release a soluble moiety, “sCX3CL1”. The research assessed three different types of RP including rd1, rd10 and Rho-/-. In the study, researchers had found that sCX3CL1 had a significantly increased number of cones remaining in the central retina (P < 0.0001) and this supported the idea that there was a potential therapeutic effect of sCX3CL1 in three RP models. In addition, ERGs for these studies have also had an improved cone-mediated visual function. In the report, the researches commented that, “while the mechanism by which AAV8-sCX3CL1 saves cones remains to be elucidated, our findings suggest that sCX3CL1 gene therapy could be beneficial for a wide range of patients with RP, and potentially for other patients with inflammatory processes that affect vision or other areas of the CNS.”


The multiple genes, and the various mutations in such genes, show that there is a significant challenge to develop new medical treatments. It appears that time, money and logistics are unlikely to be feasible to develop the requested number of medical interventions. However, cone cell rescue may provide an attractive option to maintain enough cells to allow useful vision. In a summary of the significance commented on the PNAS study (ref), the research paper stated: “Development of therapies that preserve cones and vision in patients with RP, particularly in a mutation-independent manner, would benefit from a greater understanding of the underlying pathological mechanisms”.