Treatments for spinal cord injury: is there hope in neurosteroids?
In this review, we describe the current therapeutic strategies to find a cure for paralysis. We use the example of DHEA, a neurosteroid normally produced in the developing neural tube, to raise the hypothesis that such a class of molecules, capable of modulating proliferation of committed neural precursors, could serve as an environmental cue in the adult injured spinal cord to promote re-population of CNS lesion with endogenous dormant precursor cells. Such mechanism may be a part of the natural response to heal the injured CNS and promote recovery of function, suggesting that neurosteroid-treatment could be a promising and novel therapeutic avenue for SCI. We will review pertinent biological activities of DHEA supporting this hypothesis, demonstrate that such activities, dependent on an intact sonic-hedgehog pathway, are responsible for the motor and bladder functional recovery observed after DHEA-treatment in the adult injured spinal cord. We will also raise the current limitations to further development of DHEA- or other neurosteroid-treatments as drug candidates, including the urgent need to further document DHEA long-term safety in CNS indications.
Compagnone
Nathalie A
NA
University of California San Francisco, Laboratory for Spinal Cord Development and Regeneration, Department of Neurological Surgery, CA, USA. icdd-meyreuil@orange.fr
D000818:Animals; D017690:Cell Transplantation; D002986:Clinical Trials as Topic; D006801:Humans; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism; D009416:Nerve Regeneration; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology; D013256:Steroids / Q000627:therapeutic use*
D013256:Steroids