Federal Grant Award Summary

The University of Illinois received a $400,825 Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853), effective May 1, 2026 through April 30, 2027. The award supports basic research to elucidate the mechanisms of axonal degeneration in hereditary spastic paraplegia (HSP), specifically investigating the interplay between autophagy-lysosomal defects and mitochondrial dysfunction in patient-derived neurons. Research deliverables include mechanistic characterization of how mutations in SPG11 and ZFYVE26 genes impair spatacsin and spastizin proteins, leading to axonal pathology, utilizing induced pluripotent stem cell (iPSC)-based disease models.

The research comprises three primary aims: identifying the role of spatacsin and spastizin in axonal and autophagy-lysosomal defects of cortical projection neurons; determining the interplay between autophagy-lysosomal dysfunction and impaired mitochondrial dynamics; and establishing how these pathological processes disrupt cytoskeleton organization and axonal transport. The investigation directly supports NINDS's mission to reduce the burden of neurological disease by advancing fundamental understanding of HSP pathophysiology and identifying potential therapeutic targets for nerve degeneration rescue in this debilitating inherited disorder.