Federal Grant Award Summary

The National Institute of Neurological Disorders and Stroke (NINDS) awarded Massachusetts General Hospital $161,880 on May 1, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853) to investigate the TTYH3 protein and its relationship to CLN3 Batten disease. This one-year project grant, concluding April 30, 2027, supports research into a rare lysosomal disorder affecting approximately 1 in 100,000 children that causes progressive blindness, seizures, cognitive decline, and early mortality. The research team will develop critical investigative tools including TTYH3/TTYH3 knockout mouse models and human induced pluripotent stem (IPS) cell-based systems to study the protein's subcellular localization and test the hypothesis that TTYH3 functions as a novel lysosomal lipid transporter in the context of CLN3 disease.

The project directly responds to the National Institutes of Health Notice of Funding Opportunity PAR-25-122 targeting research on understudied proteins linked to rare diseases. By characterizing TTYH3 elevation in both neuronal and microglial cells—where proteomics studies identified 10- to 20-fold increases in diseased samples—the research addresses a gap in understanding the neuroimmune mechanisms underlying neurodegeneration in CLN3 disease. These research models and characterization data will provide the scientific community with essential resources for further investigations into disease pathophysiology and potential therapeutic interventions.