Federal Grant Award Summary

The National Institute of Neurological Disorders and Stroke (NINDS) awarded Massachusetts General Hospital a Project Grant of $642,454 on April 15, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program. The grant supports a five-year research initiative concluding February 28, 2031, to develop a novel combinatorial therapeutic approach for familial dysautonomia (FD), a rare neurodegenerative inherited disorder caused by mutations in the ELP1 (elongator acetyltransferase complex subunit 1) gene. The research combines two complementary strategies: a small molecule splicing modulator compound that rapidly rescues defective ELP1 gene splicing, and a permanent genome editing approach using base editing technology to correct the underlying FD mutation.

The project will generate in vivo proof-of-concept data demonstrating the efficacy and synergistic effects of this dual-treatment strategy in a humanized mouse model of FD. By leveraging the rapid systemic action of the splicing modulator with the durable, long-term correction provided by gene editing, the research aims to significantly attenuate systemic disease manifestations while potentially reducing compound dosing requirements and associated toxicity. This translational research effort addresses a critical medical need, as no treatments currently exist to halt the progressive neuronal loss characteristic of FD, which affects patients with diminished pain perception, blood pressure instability, proprioceptive ataxia, and progressive retinal degeneration.