Poster #092
Directing Neuroprotective Neural Stem Cells to Dying Motor Neurons in ALS
Mentors: Evan Y. Snyder, MD, PhD and Kartik S. Sundaram, BA, BS
Abstract: Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease caused by progressive motor neuron death in the brain and spinal cord. Prior Snyder Lab work has shown human neural stem cells (hNSCs) intrinsically migrate to pathological regions in the SOD1G93A ALS mouse model and are neuroprotective. hNSC’s “pathotropism” is due, in part, to CXCR4 receptor activation on hNSCs. CXCR4 binds the inflammatory cytokine SDF1α. However, adding SDF1α to facilitate hNSC migration would create undesired toxicity. Our group created a synthetic CXCR4 agonist, SDV1a, engineered to possess the trophic aspects of SDF1α by maximizing its CXCR4 binding motif while truncating its signaling motif (eliminating inflammation). SDV1A promotes hNSC migration toward ALS pathology in-vitro and in-vivo without inflammation. To ascertain clinically-relevant SDV1a dosing and SDV1a fate, we’ve assessed its intra-hNSC internalization using live-cell imaging in-vitro, furthering our understanding of this novel cell-drug interaction which possesses much therapeutic potential.