FirstString Research, Inc — Department of Health and Human Services SBIR Phase I: N

Description

PROJECT SUMMARY ABSTRACT FirstString Research has identified a novel peptide that shows therapeutic potential in the treatment of age related macular degeneration AMD This Phase I SBIR will assess both the feasibility and mechanism of action involved in the topical delivery of a synthetic connexin based peptide aCT for the treatment of AMD AMD is a retinal disease in patients who progressively lose their central vision through pathological and damaging conditions of the macula and the development of VEGF mediated choroidal neovascularization CNV Approved therapeutics that target VEGF are the therapeutic option of choice but are costly require chronic highly invasive intravitreal injections have safety concerns and are modestly effective An effective safe topical formulation for the treatment of AMD represents a significant and much needed innovation aCT is a small soluble peptide based on the C terminal sequence of connexin engineered to directly translocate into cells without the requirement of any potentially toxic compound for topical or intracellular drug delivery When applied topically on skin wounds aCT safely promotes healing reduces inflammation and scarring and promotes complex tissue regeneration aCT peptideandapos s unique properties in skin wound healing and tissue regeneration combined with evidence that the non vascular components of AMD correspond to a submacular wound healing or tissue repair response suggest therapeutic opportunity in the treatment of AMD Preliminary studies show that topical application of an aCT eyedrop formulation reduces CNV and stabilizes the barrier function of the retinal pigment epithelium RPE in mouse models mimicking the pathophysiology AMD The goal of this proposal is to evaluate the therapeutic potential and mechanism of action of the aCT peptide in an eye drop formulation as a novel minimally invasive therapy to prevent the progression of AMD and restore retinal function To accomplish this goal FirstString Research will Further delineate aCT andapos s therapeutic potential and mechanism of action in preserving RPE barrier function and inhibiting CNV using mouse models of AMD where aCT might reduce inflammation by reducing Cx hemichannel activity and stabilize tight junction integrity Experiments will include the investigation of potential synergy between aCT and anti VEGF therapeutics Identify the dose in which aCT can be delivered by eye drops to achieve efficacy in a rabbit model of CNV and examine potential side effects in uninjured eyes The completion of these aims will provide sufficient data to demonstrate therapeutic potential and mechanism of action of aCT in stabilizing the RPE network in order to support formulation optimization and further validation in additional large animal efficacy and PK toxicity studies in a Phase proposal PROJECT NARRATIVE Age related macular degeneration AMD affects approximately million people worldwide and is a leading cause of vision loss Current therapeutic options limit disease progression but require frequent invasive intravitreal injections and are associated with safety concerns The goal of this proposal is to initiate the clinical development of a topical eye drop containing a small regulatory peptide aCT that that stabilizes barrier function of epithelia and combats AMD pathophysiology Therapeutic development of aCT will offer an easier safer cheaper and effective therapeutic option for the ophthalmic management of AMD