Federal Grant Award Summary

The National Institute of Neurological Disorders and Stroke (NINDS) awarded $484,000 in Project Grant funding to the Sloan-Kettering Institute for Cancer Research, effective May 1, 2026 through April 30, 2028, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853). The research focuses on characterizing and inhibiting the interactions of ADAM17 (a disintegrin and metalloproteinase 17), an alpha-secretase enzyme, with the neuronal-myelin signaling complex in the context of spinal cord injury. The project investigates how myelin-associated inhibitors trigger axonal growth inhibition through a receptor/co-receptor complex and examines ADAM17's specific role in cleaving P75 receptor when it is part of this signaling complex.

The research deliverables include detailed molecular characterization of the interactions between myelin-based ligands (myelin-associated glycoprotein, NOGO-A, and oligodendrocyte myelin glycoprotein) and the neuronal receptor complex, identification of P75's role in mediating and stabilizing these interactions, determination of how different myelin ligands activate the alpha-secretase ADAM17, and development of anti-ADAM17 monoclonal antibodies to inhibit P75 cleavage and reverse neurite outgrowth inhibition. The ultimate goal is to advance therapeutic strategies for promoting axonal regeneration following spinal cord injury by blocking the pathological signaling cascade that prevents nerve fiber regrowth.