Atsena Unveils Gene Therapy for Retinal Eye Disease with Promising Profile

Eye Research

On Monday, Atsena Therapeutics announced the early development of a novel spreading capsid as part of its initiative to develop a gene therapy treatment for X-linked retinoschisis. While it has yet to reach clinical trials, preclinical results with the company’s specially-tailored adeno-associated virus have been fortuitously auspicious.

Retinoschisis is a retinal disorder wherein the retina splits into two layers: an inner layer of receptor cells, and an outer layer of associated support cells. If formed near the center of the visual field, these splits create cysts that damage surrounding nerve cells. It is also possible for this condition to develop into full-blown retinal detachment.

Many forms of retinoschisis are simply degenerative, but X-linked retinoschisis (XLRS) is genetic and identified in about one in every 5,000 to 25,000 juvenile males around the time they reach grade school. Additionally, while the development of total blindness is rare, there are essentially no treatments for this condition.

The only current treatment options available are, one: glasses, which cannot correct or repair vision loss due to nerve damage, and two: surgery, which risks causing increased detachment. Furthermore, intravitreal vector treatments like this one usually risk inflammation immune responses that can cause more damage to nerves.

However, Atsena’s novel spreading capsid introduces a gene therapy program potentially capable of re-introducing an unmutated copy of the RS1 gene into retinal cells. Using AAV.SPR, Atsena’s own adeno-associated virus model, florescent-tagged copies of the RS1 gene were injected into the central retina of macaques.

The expression of RS1 was then found in other retinal regions, including the fovea, where vision is the clearest. This suggests that the capsid was successful in spreading copies of the RS1 gene laterally via transduction, even to areas of the retina not affected by retinoschisis. Ideally, this would mean that these areas could be resilient against, and possibly even immune, to future retinoschisis.

Further study in mouse models showed that the subretinal delivery of RS1 using AAV.SPR could not only restore the retinal structure from its schisms, but also induce a long-term phenotypic rescue of at least six months after administration of the treatment.

Whereas the transduction of prior intravitreal treatments has been inefficient and often risks an inflammatory immune response that can cause even more damage to nearby nerves, Atsena’s unique vector does not appear to cause inflammation and possesses an unforeseen efficacy in spreading a functional RS1 gene throughout the retina.

“Our novel spreading capsids may be the key to overcoming the challenges associated with intravitreally delivered AAVs in the treatment of XLRS, such as inefficient photoreceptor transduction and inflammation,” said Atsena Chief Scientific Officer Linda B. Couto, Ph.D. in a statement.

While clinical trials are not yet underway, Atsena has already met with the U.S. Food and Drug Administration to discuss the development program in an effort to begin advancing in that direction.

In the meantime, Atsena is also pursuing gene therapy treatments for other inheritable eye diseases, including Usher Syndrome 1B and Leber Congenital Amaurosis 1, the latter of which currently has an experimental treatment undergoing Phase I/II clinical trials.

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