Project Grant R03NS150998

The National Institute of Neurological Disorders and Stroke, a component of the Department of Health and Human Services National Institutes of Health, awarded Emory University $156,500 on September 1, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853) to generate and characterize a novel conditional SPTLC1 mouse model investigating sphingolipid dysregulation in amyotrophic lateral sclerosis.

The project will develop the first conditional SPTLC1 deletion-exon-2 mouse model to enable precise dissection of SPTLC1 function in the central nervous system. SPTLC1 encodes the long-chain base subunit of serine palmitoyltransferase, which catalyzes the first and rate-limiting step in sphingolipid biosynthesis. Mutations in SPTLC1 have been linked to hereditary sensory and autonomic neuropathy type I and juvenile ALS; global SPTLC1 knockout mice are embryonically lethal, preventing study of its physiological role. The targeted exon 2 deletion produces a protein retaining partial localization and residual enzymatic activity, modeling the partial serine palmitoyltransferase dysfunction observed in human ALS disease. The project will reveal how disrupted sphingolipid homeostasis drives neurodegeneration and establish a foundational tool to study metabolic mechanisms underlying ALS.

Performance occurs in Atlanta, Georgia. The period of performance runs from September 1, 2026, through August 31, 2028. The award is classified as a Project Grant, an assistance type supporting extramural research.