Gene editing for treatment of retinitis pigmentosa

This technology uses CRISPR-Cas9 gene editing to target prolyl hydroxylase (PHD2) to slow the progression of retinitis pigmentosa (RP).

Unmet Need: Effective treatment for retinitis pigmentosa

Retinitis pigmentosa (RP) is a group of genetic neurodegenerative eye diseases in which metabolic dysregulation in photoreceptors results in their degeneration, leading to vision impairment. Similar patterns of metabolic dysregulation can also be found in other neurodegenerative diseases, including age-related macular degeneration, Alzheimer’s Disease, and Parkinson’s Disease. There are currently no effective treatment options for most types of RP, as well as for these related neurodegenerative diseases. As such, there is a clear need for novel approaches for treating neurodegeneration.

The Technology: CRISPR reprogramming of metabolic regulation to treat retinitis pigmentosa

This technology describes the use of CRISPR gene editing to target metabolic dysregulation in retinitis pigmentosa (RP). Specifically, this technology uses an adeno-associated viral (AAV) vector to deliver CRISPR-Cas9 guide RNAs targeting the prolyl hydroxylase (PHD2) gene in the retina. Inhibiting this gene promotes the survival of rod and cone cells by reprogramming metabolic pathways dysregulated in RP. Through this reprogramming process, this technology slows the progression of RP disease without inducing cytotoxicity.

This technology has been validated in RP preclinical mouse models.

Applications:

• Pharmacological treatment for retinitis pigmentosa (RP)
• Treatment approach for other neurodegenerative diseases associated with metabolic dysregulation
• Research tools to investigate the role of metabolism in retinal degeneration

Advantages:

• Capable of treating multiple different forms of RP, regardless of specific genetic causes
• Removes the need for individualized treatments for different types of RP or for the need to identify/diagnose RP subtype in patients
• Reprogramming retinal metabolism can be useful in treating several other retinal diseases

Lead Inventor:

Stephen H. Tsang, M.D., Ph.D.

Patent Information:

Patent Pending

Related Publications:

• Nolan ND, Cui X, Robbings BM, Demirkol A, Pandey K, Wu WH, Hu HF, Jenny LA, Lin CS, Hass DT, Du J, Hurley JB, Tsang SH. “CRISPR editing of anti-anemia drug target rescues independent preclinical models of retinitis pigmentosa.” Cell Rep Med. 2024 Apr 16;5(4):101459.

Tech Ventures Reference:

• IR CU23293

• Licensing Contact: Kristin Neuman