A gene therapy based on channelrhodopsin-2, from green algae, already has shown efficacy in restoring light sensitivity to animals that have lost photoreceptors. The product, RST-001, is RetroSense Therapeutics LLC's lead candidate in a pipeline targeted at certain types of retinal degeneration.

Degenerative retinal conditions like retinitis pigmentosa (RP) cause photoreceptors – known as rods and cones – to die. That loss eventually leads to blindness. In the case of RP, more than 100 different gene defects contribute to the condition, which at first blush would seem to make it a poor candidate for gene therapy.

However, Wayne State University researcher Zhuo-Hua Pan has shown that the algae protein channelrhodopsin-2 can confer light sensitivity on retinal cells. The therapy does not restore rods and cones. Rather, it bypasses them, creating new photoreceptors in the surviving secondary signal transmitting layer of the retina.

The gene is encapsulated in the AAV2 (adeno-associated virus 2) vector and administered by injection into the eye.

"The secondary signal layer begins to pull double duty, as it senses light signal coming in and sends it to the visual cortex," Sean Ainsworth, CEO of RetroSense, told BioWorld Today. "There's a pretty tremendous body of literature on the efficacy of this approach in animal studies."

That mode of therapy was pioneered with the use of retinal implants that used electrodes to signal those same cells. Ainsworth described the channelrhodopsin-2 therapy as a next generation of the same approach.

The treatment strategy could be used in dry age-related macular degeneration as well as RP. There are no approved treatments for either of those disorders.

When Ainsworth initially assessed the technology for Wayne State University, he had no intention of spinning it out and developing it himself. He was simply providing an evaluation of its potential for the technology transfer office. "It became increasingly exciting," Ainsworth said. "I began reaching out to some folks in industry, to build not just an advisory board but a management team, and to raise capital."

Ainsworth assembled a management team including Esperion Therapeutics co-founder Thomas Rea, and former Pfizer Inc. executive Edward McGuire. Those management team members brought extensive pharma experience, including numerous successful investigational new drug applications.

Angel investors from sources in Australia, California, Missouri and Michigan have provided "pre-seed" funding for the company sufficient to begin early operations.

The name of the company, RetroSense, refers to a return – "retro" – of the visual sense.

RetroSense already has "well-established" safety data on the AAV2 delivery system because the vector has been in use for 20 years, Ainsworth said. The firm is contracting with a University of Florida researcher to manufacture the gene and vector system.

The first batch of product has been manufactured, and RetroSense has begun preclinical testing, with results expected "in the next couple of months."

Its long-term funding plan is to pursue venture capital. Ainsworth said the company already has begun that process. "We're looking to raise several million to get us into the clinic. "We're hopeful that we're going to have an announcement in the near future."

There are no drugs or other gene therapy products in the competitive landscape for RP. Retinal implant devices and stem cell therapies eventually could become competitive, if they all succeed in clinical trials.

In July 2010, R-Tech Ueno Ltd., of Tokyo, completed a Phase II study testing UF-021 (Ocuseva) in RP to improve visual function in the central part of the ocular fundus. The primary endpoint was the change in mean retina sensitivity of the central 2 degrees of the ocular fundus measured with an MP-1 microperimeter.

Twenty-four weeks from the pre-treatment level, retina sensitivity increased significantly, and there was a statistically significant lower number of patients in the treatment groups who experienced aggravation compared to placebo. The main adverse event was temporary ocular irritation.

Grenable Technologies Ltd., of Dublin, Ireland, is developing a gene therapy for RP that combines an RNAi silencing therapy targeted at mutated rhodopsin and a modified gene encoding wild-type rhodopsin. The therapy is intended to be mutation-independent.

That program is preclinical stage, and Grenable recently raised $6.8 million in Series B financing to advance toward human clinical trials. (See BioWorld Today, Nov. 16, 2011.)

Wet AMD is a very crowded area of biotech development, and there is often confusion over the difference between wet and dry forms of AMD.

The distinction is that in wet AMD, there is neovascularization of the macula, destroying the photoreceptor layer and much of the structure surrounding that layer in the macula.

Dry AMD is caused by deposits of the protein drusen that destroy the photoreceptors, leaving the signal transmitting cells intact.