Federal Project Grant Award Summary

The National Institute of Neurological Disorders and Stroke (NINDS), under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853), awarded a Project Grant of $233,550 to the Regenerative Research Foundation effective June 1, 2026, through May 31, 2028. The award supports research modeling myotonic dystrophy Type 1 and Type 2 (DM1 and DM2) neuropathology using induced pluripotent stem cell (iPSC)-derived cortical organoids. The project will generate disease and control cortical organoids from DM1 lines (238–1,600 CTG repeats), DM2 lines (8.8–11.9 KB CCTG repeats), and healthy control lines using an optimized protocol that maintains physiological expression of relevant genes.

The deliverables include detailed characterization of repeat-expansion RNA toxicity mechanisms, including tracking of RNA-foci formation, splice defects, and tau aggregation over a 6-month period using long-read RNA sequencing and quantitative neuropathology. The research will investigate whether hyperphosphorylated CELF2 (ELAV-like family 2) drives glutamatergic mis-splicing and excitotoxicity to elucidate convergent and divergent mechanisms of cortical dysfunction in DM1 and DM2. These findings are intended to enable the development of central nervous system-directed therapies for myotonic dystrophy by identifying molecular drivers of cognitive and behavioral deficits associated with these repeat-expansion disorders.