Unmet Need / Invention Novelty: Few kinases have been identified that phosphorylate eukaryotic initiation factor 2 alpha (eIF2α) and control translation in response to protein unfolding stress, a common cause of various neurodegenerative diseases. There is an unmet need to identify novel eIF2α kinase targets modulating translation and stress-responses as well as agents that target these novel kinases.
Technical Details: Researchers at Johns Hopkins have developed novel small molecule inhibitors of a newly-identified direct kinase of eIF2α. The kinase phosphorylates eIF2α in response to proteotoxic stress. The disclosed novel, small molecule inhibitors of the kinases were validated in proof-of-concept studies using human ALS patient samples and in vivo ALS mouse models, and demonstrated better efficacy than existing compounds for inhibition of the novel kinase target. Therefore, the present invention provides a promising new treatment regimen for various neurodegenerative diseases, including Alzheimer’s disease, Parkinson disease, Creutzfeldt–Jakob disease, Huntington’s disease, frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS).
Value Proposition:
- Identification of a novel eIF2α kinase target for modulating translation and stress-response
- Novel small molecule compounds for inhibition of novel eIF2α kinase
- Compounds demonstrate better kinase inhibition efficacy than existing compounds
- Applicable to a wide range of disease where eIF2α phosphorylation is implicated
Looking for Partners to: Develop & commercialize as a novel target and therapeutic for diseases where eIF2α phosphorylation is implicated
Stage of Development: Pre-clinical
Data Availability: in vitro and in vivo
