Triosephosphate isomerase (TPI) deficiency is a rare, recessive metabolic disorder that causes hemolytic anemia, locomotor impairment, increased susceptibility to infection, progressive neurodegeneration, and muscle weakness that can affect lung and heart function. Anemia due to TPI deficiency begins in infancy, and individuals with this condition rarely survive past childhood. Research suggests that mutations resulting in reduced TPI protein stability underlie disease pathogenesis. Accelerated protein turnover is a common mechanism of disease pathogenesis, and very few good targets exist for stabilizing cytosolic proteins. Although TPI deficiency is a very rare disease- around 40 cases are documented in medical literature- a treatment for it could also work for countless other biomedically important diseases with similar disease pathogenesis.
Hrizo, S. L., Eicher, S. L., Myers, T. D., McGrath, I., Wodrich, A. P. K., Venkatesh, H., Manjooran, D., Swoger, S., Gagnon, K., Bruskin, M., Lebedev, M. V., Zheng, S., Vitantonio, A., Kim, S., Lamb, Z. J., Vogt, A., Ruzhnikov, M. R. Z., & Palladino, M. J. (2021). Identification of protein quality control regulators using a Drosophila model of TPI deficiency. Neurobiology of Disease, 152, 105299. https://doi.org/10.1016/j.nbd.2021.105299
Vogt, A., Eicher, S. L., Myers, T. D., Hrizo, S. L., Vollmer, L. L., Meyer, E. M., & Palladino, M. J. (2021). A High-Content Screening Assay for Small Molecules That Stabilize Mutant Triose Phosphate Isomerase (TPI) as Treatments for TPI Deficiency. SLAS Discovery, 26(8), 1029–1039. https://doi.org/10.1177/24725552211018198