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Small molecule transthyretin ligands for the treatment of dry Age-related Macular Degeneration and orphan Stargardt Disease

总结

Age-related Macular Degeneration (AMD) is the leading cause of blindness in developing countries. AMD occurs in both dry (atrophic) and wet (exudative) forms, with dry AMD accounting for the majority of all AMD cases. However, there are currently no FDA-approved therapies for this disease. Dry AMD is caused by degeneration of photoreceptor cells in the central part of the retina, due to the buildup of cytotoxic lipofuscin bisretinoids, such as A2E, in the eye. This technology describes several small molecule inhibitors that disrupt the formation of A2E. These compounds could be used to treat dry AMD, as well as other degenerative eye diseases related to the buildup of lipofuscin bisretinoids, including orphan Stargardt disease and Best disease.

技术优势

Describes a library of transthyretin-specific compounds and their mechanism of action that decrease the amount of toxic lipofuscin buildup.Some molecules are already FDA approved for other indicationsPatent Information:Patent Pending (US 20150057320)Tech Ventures Reference: IR CU12294

技术应用

Therapeutic for ocular diseases caused by lipofuscin build-upTherapeutic for dry age-related macular degenerationTherapeutic for Stargardt diseaseTherapeutic for Stargardt-like macular dystrophyTherapeutic for Best diseaseResearch tool for characterization of the vision cycle

详细技术说明

None

*Abstract

None

*Inquiry

Ron KatzColumbia Technology VenturesTel: (212) 854-8444Email: TechTransfer@columbia.edu

*IR

cu12294

*Principal Investigation

*Publications

Petrukhin K. “New therapeutic targets in atrophic age-related macular degeneration.” Expert Opin Ther Targets. 2007 May;11(5):625-39.Dobri N, Qin Q, Kong J, Yamamoto K, Liu Z, Moiseyev G, Ma JX, Allikmets R, Sparrow JR, Petrukhin K. “A1120, a nonretinoid RBP4 antagonist, inhibits formation of cytotoxic bisretinoids in the animal model of enhanced retinal lipofuscinogenesis.” Invest Ophthalmol Vis Sci. 2013 Jan 7;54(1):85-95.Petrukhin K. “Pharmacological inhibition of lipofuscin accumulation in the retina as a therapeutic strategy for dry AMD treatment.” Drug Discov Today Ther Strateg. 2013;10(1):e11-e20.Cioffi CL, Dobri N, Freeman EE, Conlon MP, Chen P, Stafford DG, Schwarz DM, Golden KC, Zhu L, Kitchen DB, Barnes KD, Racz B, Qin Q, Michelotti E, Cywin CL, Martin WH, Pearson PG, Johnson G, Petrukhin K. “Design, synthesis, and evaluation of nonretinoid retinol binding protein 4 antagonists for the potential treatment of atrophic age-related macular degeneration and Stargardt disease.” J Med Chem. 2014 Sep 25;57(18):7731-57.Cioffi CL, Racz B, Freeman EE, Conlon MP, Chen P, Stafford DG, Schwarz DM, Zhu L, Kitchen DB, Barnes KD, Dobri N, Michelotti E2, Cywin CL, Martin WH, Pearson PG, Johnson G, Petrukhin K. “Bicyclic [3.3.0]-Octahydrocyclopenta[c]pyrrolo Antagonists of Retinol Binding Protein 4: Potential Treatment of Atrophic Age-Related Macular Degeneration and Stargardt Disease.”

国家/地区

美国