BLD-2184

BLD-2184 is a **CNS-penetrant, small-molecule inhibitor of dimeric calpains** (calcium-activated cysteine proteases), developed by Blade Therapeutics as a potential neuroprotective therapy for **inherited neurodegenerative diseases caused by genetic expansion of polyglutamine repeats**—notably **Huntington's disease** and **spinocerebellar ataxia type 3 (SCA3, Machado-Joseph disease)**. The drug is being investigated for additional neurodegenerative diseases, including **Parkinson's disease, Lewy body dementia, and multiple system atrophy**. By inhibiting calpain activity in the CNS, BLD-2184 is aimed at reducing harmful protein aggregation and promoting autophagy to ameliorate neurodegeneration. It is an oral investigational new molecular entity and has not received regulatory approval. As of 2024, BLD-2184 remains in preclinical or IND-enabling stages, with an initial phase 1 study planned for healthy volunteers[1][2][3][5][7][9][10][13].