RetroSense Therapeutics LLC, a private company based in Ann Arbor, Michigan, has announced receipt of clearance from the FDA to initiate a first-in-human study of an optogenetic strategy for the treatment of retinitis pigmentosa (RP). The company aims to deliver a “channelrhodopsin 2” gene, originally isolated from a green alga and transfect the gene into cells of the inner retina. The experimental treatment will use adeno-associated viral (AAV) vectors as the delivery tool and the trial, to be launched this Autumn, is expected to recruit approximately 15 patients to the Phase I/II study.
The growing field of optogenetics aims to use light sensitive molecules from a variety of biological sources to boost or assist residual activity in a medically relevant context. One of the most regularly used light-activated molecules is the channelrhodopsin-2 light-gated cation channels, derived from the green alga, Chlamydomonas reinhardtii. However, other groups have engineered novel optogenetic proteins that are customised to natural light intensities exploited by the human retina. The current optogenetic tool from RetroSense Therapeutics, termed RST-001, received Orphan Drug designation from the FDA in late 2014 and, according to the company, is the first in class gene therapy application of optogenetic technology.
The new approach to retinal degenerative treatment was originally pioneered by Dr. Zhuo-Hua Pan at Wayne State University and Dr. Alex Dizhoor at Salus University. Research in animal models, highlighted on the company’s website, showed that a channelrhodopsin-2 (ChR2) gene delivered to the inner retinal neurons of the common marmoset, resulted in retinal gene expression of the transgene. In addition, the research demonstrated that the intravitreal AAV-2 delivered transcripts were capable of mediating light responses recordable by electrophysiological testing. Commenting on the milestone of completing an Investigation New Drug application with the FDA, Sean Ainsworth, CEO of RetroSense stated that, “the IND for RST-001 is an important milestone for the company. This brings us one step closer to realizing our ambition of improving vision in those individuals with currently incurable blindness. There is great promise for the clinical application of optogenetics and this first human clinical trial should provide key insights into the potential for this therapy to treat diseases affecting the eye or brain.” Dr. Zhuo-Hua Pan, additionally commented that, “my hope from early on was to see our work improve the lives of people with vision defects. It is great to see the approach moving imminently into human clinical studies.”