University of Pittsburgh investigators have discovered that treatment with specific, FDA-approved therapeutics were able to promote degradation of aggregated proteins in a C. elegans model of neurodegeneration. Treatment with one or more may be used to ameliorate the symptoms of neurodegenerative diseases marked by protein polymerization and aggregation.
Description
A number of neurodegenerative disorders are associated with the presence of protein aggregates. These diseases can also be characterized as disorders of protein polymerization or protein misfolding, which can lead to protein aggregation. Alzheimer’s disease is thought to be triggered by the accumulation of aggregated proteins and worsened by aging, and evidence suggests that autophagy of these proteins can ameliorate effects on neurons. Other disorders associated with increased protein aggregates include Huntington’s disease and Parkinson’s disease, which in particular is associated with the presence of “Lewy Bodies,” abnormal aggregations that develop inside nerve cells. By promoting autophagy-inducing pathways, the toxic effect of protein accumulation can be delayed, but the load of oligomers may be too great to avoid toxic accumulation entirely.
Applications
• Treating protein aggregation disorders
• Treating traumatic brain injury
Advantages
• Potential therapeutics are already FDA approved and often available in a generic form
• Side effects are minimal
Invention Readiness
Preclinical animal data available
IP Status
https://patents.google.com/patent/US9072772B2;
https://patents.google.com/patent/US9452171B2;
https://patents.google.com/patent/US9820990B2Related Publication(s)
Oh, Y. M., Lee, S. W., Kim, W. K., Chen, S., Church, V. A., Cates, K., Li, T., Zhang, B., Dolle, R. E., Dahiya, S., Pak, S. C., Silverman, G. A., Perlmutter, D. H., & Yoo, A. S. (2022). Age-related Huntington’s disease progression modeled in directly reprogrammed patient-derived striatal neurons highlights impaired autophagy. Nature Neuroscience, 25(11), 1420–1433. https://doi.org/10.1038/s41593-022-01185-4
Lee, S. W., Oh, Y. M., Victor, M. B., Yang, Y., Chen, S., Strunilin, I., Dahiya, S., Dolle, R. E., Pak, S. C., Silverman, G. A., Perlmutter, D. H., & Yoo, A. S. (2023). Longitudinal modeling of human neuronal aging reveals the contribution of the RCAN1–TFEB pathway to Huntington’s disease neurodegeneration. Nature Aging, 4(1), 95–109. https://doi.org/10.1038/s43587-023-00538-3
