Project Grant R61HL179715

The National Heart, Lung, and Blood Institute awarded Greenstone Biosciences, Inc. $625,968 on August 1, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to conduct small-molecule drug discovery for cardiac fibrosis associated with Duchenne muscular dystrophy using artificial intelligence, machine learning, and induced pluripotent stem cell-derived organoids.

The R61 phase will perform unbiased proteomics on DMD iPSC-derived cardiomyocytes and cardiac fibroblasts to identify drug targets and elucidate pathogenic crosstalk, utilize AI with molecular docking and molecular dynamics simulations to computationally screen large compound libraries against identified targets, apply generative AI to synthesize novel compounds from a chemical space of approximately 30 billion molecules, and conduct drug screening using a bioactive compound library including nutritional and dietary supplements on DMD iPSCs to identify candidates that prevent cardiac fibrosis. The R33 phase will synthesize and evaluate lead compounds to characterize physicochemical properties including lipophilicity, pKa, and solubility, and perform validation and replication studies to confirm safety and efficacy of drug candidates identified from the AI/ML discovery work.

The award addresses the absence of specific treatments for myocardial fibrosis and dilated cardiomyopathy in DMD patients, particularly the more than 25 percent unable to tolerate corticosteroids. Work is performed at Greenstone Biosciences in Palo Alto, California. Period of performance runs through May 31, 2028.