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Project

Human ApoE and its impact on plasticity and recovery after SCI

Funder: Craig H Neilsen Foundation

Funding period
USD 300 K
Funding amount
Abstract
According to the National Spinal Cord Injury (SCI) Statistical Center there are an estimated 282,000 people in the United States with a spinal cord injury alongside 17,000+ new cases each year. Associated costs to care for this debilitated population can exceed millions of dollars in addition to the emotional costs for those injured and their loved ones. There have been promising therapeutic approaches developed in pre-clinical animal models which promote synaptic plasticity leading to functional recovery. However, some of these interventions have failed to achieve complete translational success in the human population. What is not known is the reason for this failure. One potential factor is the varied genetic background of the human population which is not completely considered in these pre-clinical studies. Indeed, there might be a genetic predisposition or aversion towards plasticity, rehabilitation, and recovery after spinal cord injury that needs to be studied in order to fully realize the therapeutic application of promising experimental interventions. In this grant application, we propose to fill this gap in knowledge and examine genetic factors which can contribute to the success or failure of therapies targeting central nervous system plasticity and ultimately, functional restoration after SCI.One promising gene to investigate which might impact these important processes used for recovery is the apolipoprotein E (ApoE) gene. Identified as a key genetic marker in predicting the development of Alzheimer’s Disease, its role in influencing the outcomes following neurotrauma and treatment has been severely understudied. In the lone human study investigating the importance of ApoE after SCI, it was determined that carrying the ApoE4 variant allele led to longer time in rehabilitation compared to those who carried the ApoE2 or 3 alleles. Despite this longer time in rehabilitation, the patients with ApoE4 had limited functional recovery compared to the other groups. In this application we will test our central hypotheses that there are varying genetic dispositions towards plasticity and sprouting in the human population and that having the ApoE4 gene is a key limiting genetic determinant of these processes, as well as neurorestoration and recovery after SCI.As ApoE4 is prevalent in 20-24% of the human population, this is an important consideration. Having expertise in experimental spinal cord injury, plasticity, and regeneration, our research group is well positioned to build upon these initial findings and test our central hypotheses. Ultimately, by recognizing that there may be genetic barriers to recovery, we can develop personalized therapies to target these populations and couple them with emerging therapeutic approaches aimed at treating SCI. (CHN: SCIRTS chn:wdg)
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System

Categories
  • FOR (ANZSRC)

    1109 Neurosciences

  • RCDC

    Injury (total) Accidents/Adverse Effects

  • RCDC

    Injury - Trauma - (Head and Spine)

  • RCDC

    Regenerative Medicine

  • RCDC

    Neurosciences

  • RCDC

    Rehabilitation

  • RCDC

    Spinal Cord Injury

  • RCDC

    Genetics

  • RCDC

    Neurodegenerative

  • HRCS HC

    Neurological

  • HRCS RAC

    2.1 Biological and endogenous factors

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science