Integrated drug discovery platform for Inborn Error of Metabolism disorders

The technology is a drug discovery platform for inborn error of metabolism disorders. It’s a yeast-based system complimented by C. elegans models as a multicellular organism. The basis for this technology is the discovery of non-protein metabolite assemblies by the Gazit lab. This is the first achievement of an in vivo model of metabolite self-assembly. It enables for the first time a drug discovery platform for inborn errors of metabolism. It has the potential to unlock some low hanging fruits in this untapped field.
Potential applications
Finding lead compounds for inborn error of metabolism disorders, including orphan diseases. Existing indications include Tyrosinemia, Phenylketonuria, Homocystinuria and Glycine encephalopathy (non-ketotic hyperglycinemia), Maple Syrup Urine Disease (MSUD), and ADA-SCID.
Stage of Development
• Four validated compounds with IC50 as low as 1.6µM
• Established collaboration with the Hospital for Sick Kids and the Institute of Medical Science, University of Toronto.
• Established IEM yeast models for Tyrosinemia, Phenylketonuria, Homocystinuria and Glycine encephalopathy (non-ketotic hyperglycinemia). A Maple Syrup Urine Disease (MSUD) model is under construction.
• Established two C. elegans models as a multicellular organism, for Tyrosinemia and Phenylketonuria, An additional model for ADA-SCID is under construction.
Intellectual Property
Ramot filed a patent application titled: “Integrated drug discovery platform for Inborn Error of Metabolism disorders” in 2018. It is now at PCT stage.

References

Gazit, E. Metabolite amyloids: a new paradigm for inborn error of metabolism disorders. J. Inherit. Metab. Dis. 39, 483-488 (2016).

Laor, D. et al. Fibril formation and therapeutic targeting of amyloid-like structures in a yeast model of adenine accumulation. Nature Commun. 10, 62 (2019).

Rencus-Lazar, S., DeRowe, Y., Adsi, H., Gazit, E. & Laor, D. Yeast Models for the Study of Amyloid-Associated Disorders and Development of Future Therapy. Front. Mol. Biosci. 6, 15 (2019).