Small molecule activators for preventing vision loss in Best vitelliform macular dystrophy

This technology is a class of small molecule activators of the Bestrophin-1 chloride channel designed to restore retinal function and mitigate vision loss in Best vitelliform macular dystrophy (BVMD).

Unmet Need: Treatment for progressive blindness in Best vitelliform macular dystrophy

Best vitelliform macular dystrophy (BVMD) causes progressive vision loss due to BEST1 gene mutations. There are currently no approved therapies on the market to stall disease progression. Existing management options rely on symptom monitoring or experimental gene therapy interventions, which can be cost-prohibitive. There is a critical need for targeted therapies that restore the underlying loss of Best1 channel function to prevent irreversible blindness in patients with BVMD.

The Technology: Small molecule activators restoring Best1 function to prevent blindness

This technology is a treatment for Best vitelliform macular dystrophy (BVMD) that utilizes synthetic small molecules to bind and activate the Bestrophin-1 (Best1) chloride channel. By targeting specific structural domains of Best1, these compounds enhance the flow of chloride ions in retinal pigment epithelium (RPE) cells to effectively mitigate progressive vision loss in BVMD. These newly synthesized small molecules are analogs of para-aminobenzoic acid (PABA) and gamma-aminobutyric acid (GABA), optimized to improve binding affinity and activation efficiency compared to the parent molecules.

This technology has been tested in vitro using human cells (HEK293), showing elevated activation of Best1.

Applications:

• Therapeutic intervention for Best vitelliform macular dystrophy (BVMD)
• Treatment of other Bestrophin-1-related retinal degenerative disorders
• Intraocular pressure (IOP) regulation in ocular diseases
• Research tool for studying the Bestrophin channel

Advantages:

• First targeted therapy for BVMD
• Enhanced potency over natural small molecule activators
• Non-invasive administration potential
• Cost-effective and scalable drug development
• Broad applicability

Lead Inventor:

Tingting Yang, Ph.D.

Patent Information:

Patent Pending

Related Publications:

• Owji AP, Dong J, Kittredge A, Wang J, Zhang Y, Yang T. “Neurotransmitter-bound bestrophin channel structures reveal small molecule drug targeting sites for disease treatment.” Nat Commun. 2024 Dec 30;15(1):10766

Tech Ventures Reference:

• IR CU25176

• Licensing Contact: Joan Martinez