Natural product promotes repair of injured spinal cord

Abstract

The regenerative capacity of axons in the mammalian CNS is poor relative to other tissues in the body such as the skin or bone. In contrast, regeneration of injured axons in the peripheral nervous system is generally more robust, which has suggested that locally produced CNS-derived growth inhibitors prevent axonal regeneration. Semaphorin3A (Sema3A) is a key inhibitor of axonal regeneration and a small-molecule inhibitor of Sema3A (SM-216289, isolated as a natural product from fungal fermentation) has been shown to promote CNS repair in adult rats subjected to spinal cord transection. Treatment with SM-216289 caused increased regeneration of injured axons, Schwann cell-mediated myelination, enhanced angiogenesis and decreased apoptotic cell death. This study validates both Sema3A as a therapeutic target and suggests that optimisation of compounds based on this pharmacophore may have use in the treatment of spinal cord injury in man.

Keywords::

• functional axonal regeneration
• natural product
• semaphorin inhibitor
• spinal cord injury