Spinal Cord Regeneration

Spinal cord regeneration has long been the holy grail of neuroscience. Until recently, most scientists regarded efforts to regenerate the spinal cord to be a futile exercise, not only because they believed that spinal axons cannot grow, but also because they did not think axons would be able to reconnect with the correct neurons even if they could grow. Most spinal cord regeneration research focused on why central axons cannot grow. Three theories dominate the field. The first theory hypothesizes that the spinal cord expresses proteins that inhibit axon growth. The second theory posits that a glial scar forms at the injury site and prevents axon growth. The third theory postulates that ability of neurons to grow is genetically shut off after birth. These theories emphasize factors that prevent regeneration and have identified important therapeutic targets, such as Nogo antibodies, Nogo receptor blockers, chondroitinase, and drugs that increase cyclic adenosine monophosphate and activate Akt/mammalian target of rapamycin. Many data support each theory, but also suggest that multiple mechanisms prevent spinal cord regeneration. Several cell transplants have been reported to facilitate spinal cord regeneration, including fetal neural tissues, olfactory ensheathing glia, umbilical cord blood, and bone marrow mononuclear cells. Most of these cells are probably improving the environment of the spinal cord and providing growth factors to encourage regeneration. Most scientists believe that many factors modulate spinal axon growth, and combination therapies will be necessary to achieve functional regeneration of the spinal cord. Some therapies are being tested in clinical trials, including the myelin-associated growth inhibitor blockers such as Nogo antibody and the rho inhibitor Cethrin, bone marrow stromal cells, umbilical cord blood mononuclear cells, and lithium. Within this decade, we are likely to identify the first effective regenerative therapies for chronic spinal cord injury.