Identifying drugs to amplify neural recovery
Funded in: 2021, 2022, 2023
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Problem: The corticospinal system is the most refractory to spontaneous regeneration
Target: Combination of stem cell grafts plus intensive rehabilitation
Goal: Develop novel strategies to improve functional outcomes
Spinal cord injury (SCI) is a devastating disease where patients experience permanent functional impairment below the level of injury for the duration of their life. To date, rehabilitation is the most promising and widely applicable therapeutic intervention after SCI that shows beneficial outcomes in individuals that have some neurologic sparing at and below the level of injury. The corticospinal system is the primary motor projection in humans, but it is also the most refractory to spontaneous regeneration and requires external intervention, such as stem cell grafts for robust regeneration (Kadoya, Nature Medicine 2016). In this study, the neuroscientists hypothesize that the combination of stem cell grafts placed into the lesion cavity plus intensive rehabilitation will improve outcomes after SC
They will first identify the molecular changes that corticospinal neurons undergo from early to late stages of rehabilitation, termed the rehabilitation transcriptome. The researchers will compare this to animals that receive no rehabilitation and/or no stem cell grafts, to determine the full benefit of each therapeutic strategy.
Once they’ve identified which genes are active during rehabilitation and stem cell implants, a cloud-based infrastructure will help link this genetic code to pharmacological drugs that have similar genetic codes.
Once top drugs have been identified, these predicted pharmacological compounds would be tested in animal models of spinal cord injury to determine their therapeutic value. If successful, this work could develop novel strategies to improve functional outcomes after SCI and take a rapid path towards human intervention, as some of these drugs are already FDA approved.