Regulation of cholesterol efflux for treating macular degeneration

This technology is a method to treat and prevent blindness due to macular degeneration by regulating cholesterol efflux by preventing drusen formation.

Unmet Need: Effective treatment and cure for macular degeneration

Macular degeneration (MD) is the leading cause of blindness worldwide. However, there is currently no cure and treatment options are limited to symptom alleviation. MD is characterized by lipid droplets, or drusen accumulation in the retinal pigment epithelium (RPE). Despite extensive research, the pathogenesis of drusen formation remains unclear. Although drusen are associated with normal aging, they can be associated with age-related MD depending on their size, number, location, and type. As such, targeting the mechanism of drusen formation may elucidate the development of effective treatments against MD and other types of retinal neurodegenerative diseases.

The Technology: Cholesterol-regulating enzyme and pathway for treating macular degeneration

This technology is a non-gene-specific therapy for retinal pigment epithelium (RPE) dysfunction in MD patients that uses adeno-associated viral (AAV) vectors to promote the expression or activity of carboxylesterase 1 (CES1) in RPE cells. The technology encompasses both direct overexpression of CES1 using gene therapy techniques as well as indirect up-regulation of CES1 activity via treatment with epidermal growth factor (EGF) or other epidermal growth factor receptor (EGFR) signaling pathway agonists. Promotion of CES1 activity in RPE cells via CES1 overexpression or EGFR inhibition has the potential to reverse, prevent, or slow vision loss from patients suffering from MD and related neurological disorders with RPE dysfunction.

This technology has been validated with human iPSCs, donor RPE cells, and human iPSC-derived retinal organoids.

Applications:

• Treatment and preventative for macular degeneration (MD), and Doyne Honeycomb Retinal Dystrophy (DHRD)
• Treatment for other types of retinal neurodegenerative diseases
• Research tool for studying retinal pigment epithelium (RPE) function
• Platform for drug screening
• Research tool for regulation of cholesterol efflux in retinal pigment epithelium cells
• Research tool for studying the expression and activity of carboxylesterase 1 (CES1) and EGFR signaling

Advantages:

• Specifically targets mechanistic pathways that cause drusen formation
• Enables potential delay of onset, treatment, prevention, or treatment of MD
• Broadly applicable therapeutic for multiple forms of MD and RPE dysfunction
• Demonstrates relationship between cholesterol efflux, lipid accumulation, and RPE dysfunction

Lead Inventor:

Stephen H. Tsang, M.D.

Patent Information:

Patent Pending (US20240050590)

Related Publications:

• Tsai YT, Li Y, Ryu J, Su PY, Cheng CH, Wu WH, Li YS, Quinn PMJ, Leong KW, Tsang SH. “Impaired cholesterol efflux in retinal pigment epithelium of individuals with juvenile macular degeneration.” Am J Hum Genet. 2021 May 6; 108(5): 903-918

Tech Ventures Reference:

• IR CU21299

• Licensing Contact: Kristin Neuman