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CMCC 3085

Novel pathway and treatments for pathological retinal angiogenesis

Inventors: Ye Sun, Lois Smith

Invention Types: Therapeutics

Research Areas: Ophthalmology

Keywords: Anti-angiogenesis, Small Molecule/Drug, Cell Signaling, Gene Therapy

For More Information Contact:  Yen, Alan

 

Invention Description:

Many eye diseases – including age-related macular degeneration (AMD) and macular telangiectasia – share secondary pathologies that cause vision loss. Specifically, pathological retinal angiogenesis causes vision loss because excessive vascularization blocks photoreception by cones and rods and activates immune cells where they are normally absent. The current standard of care for AMD, anti-VEGF treatment, is ineffective for many patients and does not address the immune inflammatory responses prevalent in many diseases states.

Dr. Smith’s group has identified c-Fos, a regulator of many inflammatory signals, as a key upstream target to treat the bimodal pathologies associated with retinal vascularization. In vivo experiments showed that inhibition of c-Fos, with small molecules or photoreceptor-specific AAV-mediated knockout, decreased induction of interleukin-6 (IL-6) and increased production of endogenous Suppressor of Cytokine Signaling-3 (SOCS3). This resulted in dual suppression of Signal Transducer and Activator of Transcription 3 (STAT3) and limited the production of VEGF-A, leading to a reduction in pathological neovascularization and rescuing visual function in a mouse model.

Targeting c-Fos is a novel way to potentially prevent vision loss secondary to pathological retinal angiogenesis and may have broad therapeutic value for other vascular disorders involving photoreceptor microenvironmental inflammation.

Applications:

• Regulation of retinal vascular proliferation to treat eye diseases, including AMD and macular telangiectasia
• Platform to find additional pathway targets investigation and drug discovery

Competitive Advantages:

• Bimodal treatment for many vascular diseases
• Small molecule and RNA knockout therapeutics
• Novel pathway of pathological retinal angiogenesis

Business Opportunity:

License, sponsored research, collaboration

Key Publications: Sun Y, Lin Z, Gong Y, et al. Inflammatory signals from photoreceptor modulate pathological retinal angiogenesis via c-Fos. J. Exp. Med. 2017 Jun 5;214(6)

IPStatus: Pat. Pend.