The Eyes Have It: A Unique Therapy for Ocular Disorders


By Staff Reports

(DGIwire) – We depend on our vision to complete everyday simple tasks. Unfortunately, there are many ocular disorders that can cause problems in both the front and the back of the eye that interfere with our vision and may prevent our ability to function. The cornea is the eye’s outermost layer, according to the National Eye Institute; it is the clear, dome­shaped surface that covers the front of the eye and plays an important role in clear vision. As you can imagine, the surface of the cornea is easily susceptible to injury and wounds and subsequent scarring. The retina is the light-sensitive layer of tissue at the back of the eyeball. In the case of advanced wet age-related macular degeneration, continued damage may cause scarring on the retina, which can contribute to vision loss.

In the quest to develop better treatments for both classes of ocular disorders, researchers have taken inspiration from a medical breakthrough known as RNA interference (RNAi), in which a particular “messenger RNA” can be destroyed before it is translated into a protein. Since the overexpression of certain proteins plays a role in many conditions, including those of the eye, the ability to inhibit gene expression with RNAi provides a potentially powerful tool to treat human disease.

“Many eye conditions may come to be treated by therapies developed as a result of better understanding of the RNAi mechanism,” says Dr. Geert Cauwenbergh, President and CEO of RXi Pharmaceuticals. “Our RNAi platform is dramatically improved with respect to cellular uptake as compared to the original RNAi compounds tested clinically, and as such has (significantly) improved potential to show positive results in clinical trials.”

RNAi is the foundation of RXi’s novel therapeutic self-delivering RNAi platform, called sd-rxRNA®. The first of the compounds created using this platform, RXI-109, is in development to target connective tissue growth factor (CTGF), a key regulator of fibrosis and scar formation in the eye and skin. The company believes the therapeutic reduction of CTGF could help reduce loss of vision associated with retinal scarring. To support moving RXI-109 forward into clinical studies to evaluate the potential to reduce the formation of retinal scars, work conducted in mouse and rabbit eye by intravitreal injection showed no overt toxicity following sd-rxRNA® treatment. Dose-dependent reduction of CTCF has also been demonstrated in vivo in the non-human primate retina and cornea.

In late 2015, RXi initiated a Phase 1/2 clinical trial, RXI-109-1501. This multidose, dose escalation study is evaluating treatment with RXI-109 in patients with subretinal scarring associated with advanced wet AMD. The primary objective is to evaluate the safety, tolerability and pharmacokinetics of single and multiple doses of RXI-109 when administered by intravitreal injection. Moving from the back to the front of the eye, the company has also successfully demonstrated the topical delivery of sd-rxRNA® to epithelial wounds on rabbit corneas. The topical administration of sd-rxRNA® in a gel formulation was found to result in cellular delivery to all layers of the corneal stroma within 24 hours of administration.

“Our work to date suggests that RXI-109 has potential as a therapeutic for retinal and corneal indications with a scarring component,” adds Dr. Cauwenbergh. “We are looking forward to additional results from our ongoing and future studies to learn more about what this sd-rxRNA® can do to alleviate the scarring potential associated with a variety of ocular conditions.”

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