This technology is a class of small molecule compounds that block TIA1-driven stress granule formation and the pathological protein aggregation underlying neurodegenerative diseases such as ALS, frontotemporal dementia, and Alzheimer’s disease.
\r\rNeurodegenerative diseases such as ALS, frontotemporal dementia, and Alzheimer’s disease remain without treatments that meaningfully slow their progression. Approved drugs, including riluzole and edaravone for ALS and cholinesterase inhibitors and anti-amyloid antibodies for Alzheimer’s, address symptoms or a single downstream target rather than the protein aggregation and RNA dysregulation that drive these disorders. Efforts to modulate this pathology by inhibiting upstream kinases reduce stress granule formation but lack specificity and carry significant toxicity. No available therapy directly targets the stress granule nucleators responsible for pathological protein aggregation.
\r\rThese compounds inhibit the self-multimerization of TIA1, a prion-related RNA-binding protein that nucleates stress granules during cellular stress. By preventing TIA1 multimerization, the compounds block stress granule assembly and stop the recruitment of aggregation-prone proteins implicated in neurodegenerative diseases into these structures. In some cases, these compounds can also accelerate the disassembly of aggregates that have already formed. Initially identified through a high-throughput screen, the series has been extended through the synthesis of novel chemical analogs with improved structure-activity profiles.
\r\rThe compounds have been validated in human and mouse cell lines and in human motor neurons.
\r\rPatent Pending
\r\rIR CU16219, CU26002
Licensing Contact: Jerry Kokoshka