REGENERATIVE AND DIAGNOSTIC STRATEGIES FOR NEURODEGENERATIVE DISEASES

We are utilizing rodent neural progenitor (NPCs) and human neural stem cells (hNSCs) as therapeutic interventions to promote anatomical and functional repair following spinal cord injury. We have shown that NPC/hNSCs grafted into sites of spinal cord injury: (1) integrate fully into the host spinal cord tissue, (2) differentiate into neurons and glia cells, (3) self-organize into organotypic domains, (4) send out axons over long distances throughout the spinal cord grey and white matter, neglecting the inhibitory white matter environment, (5) innervate host grey matter, thereby acting as functional synaptic relays to elicit functional recovery, and (6) have the ability to support regeneration of corticospinal axons. Recently, we published the regeneration transcriptome of the corticospinal neuron (Poplawski et al., nature 2020). Regeneration of this critical system for voluntary motor functions in humans is dependent on a transcriptomic reversal to a neurodevelopmental state. Our future goals are to finetune NPC/NSC grafts combined with gene therapy approaches to design interventions that promote functional recovery following spinal cord injury. In the second major line of research, we are developing new tools for biomarker discovery for neurodegenerative diseases utilizing extracellular vesicles as biomarker-carriers. Ultimately, we aim to synergize these two areas of research to co-develop therapies and biomarkers that can be utilized as a read out to gage the success of clinical trials.

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