Metabolite biomarkers for improved glaucoma risk prediction and treatment

This technology is an approach for improved glaucoma risk prediction and treatment that measures the levels of glycolysis-related metabolites.

Unmet Need: Glaucoma early detection and intervention method

Glaucoma is an incurable, neurodegenerative disease that is the leading cause of permanent blindness. With current tools, glaucoma is difficult to diagnose until serious visual impairment arises; therefore, early detection and intervention methods are needed. Polygenic risk scores are used to stratify individuals based on their risk of developing glaucoma. However, some individuals with the highest risk never develop the disease. Understanding the rationale behind this resilience in high-risk individuals and leveraging this knowledge to treat patients with the disease is necessary.

The Technology: Improved metabolite-based risk predictor and treatment for glaucoma

This technology is a metabolomics-based enhancement to polygenic risk scoring for glaucoma. It leverages elevated levels of glycolysis-related metabolites, which are associated with increased resilience in individuals genetically predisposed to the disease. By integrating these metabolite levels with traditional polygenic risk scores, the approach enables more refined risk prediction and helps identify individuals who may be more resistant to developing glaucoma. Additionally, the technology includes functional validation through dietary pyruvate supplementation in mice, demonstrating the potential of these metabolites to reduce glaucoma symptoms and serve as a therapeutic strategy.

This technology has been validated in a humanized mouse model.

Applications:

• Risk prediction for glaucoma
• Therapeutic strategy for glaucoma
• Predictor of glaucoma resilience in high-risk patients

Advantages:

• Improved glaucoma risk assessment
• Incorporates both environmental and genetic risk factors
• Identifies biomarkers associated with resilience
• Enables a potential therapeutic strategy for glaucoma

Lead Inventor:

Simon John, Ph.D.

Patent Information:

Patent Pending

Related Publications:

• Li K, Tolman N, Segrè AV, Stuart KV, Zeleznik OA, Vallabh NA, Hu K, Zebardast N, Hanyuda A, Raita Y, Montgomery C, Zhang C, Hysi PG, Do R, Khawaja AP, Wiggs JL, Kang JH, John SWM, Pasquale LR; UK Biobank Eye and Vision Consortium. “Pyruvate and related energetic metabolites modulate resilience against high genetic risk for glaucoma.” Elife. 2025 Apr 24; 14: RP105576.

• De Moraes CG, John SWM, Williams PA, Blumberg DM, Cioffi GA, Liebmann JM. “Nicotinamide and Pyruvate for Neuroenhancement in Open-Angle Glaucoma: A Phase 2 Randomized Clinical Trial.” JAMA Ophthalmol. 2022 Jan 1; 140(1): 11-18.

• Harder JM, Guymer C, Wood JPM, Daskalaki E, Chidlow G, Zhang C, Balasubramanian R, Cardozo BH, Foxworth NE, Deering KE, Ouellette TB, Montgomery C, Wheelock CE, Casson RJ, Williams PA, John SWM. “Disturbed glucose and pyruvate metabolism in glaucoma with neuroprotection by pyruvate or rapamycin.” Proc Natl Acad Sci U S A. 2020 Dec 29; 117(52): 33619-33627.

Tech Ventures Reference:

• IR CU25150

• Licensing Contact: Kristin Neuman