Dr. Arthur Brown discusses his passion for spinal cord injury research, what his lab is currently working on and how he hopes to see his research impact spinal cord injury in the future. The body’s response to spinal cord injury includes processes that promote regeneration and processes that not only inhibit regeneration but actually increase damage. The balance of these pro– and anti-regenerative forces determines the final clinical result. At Robarts Research in Canada, they have three major areas of research focused on identifying and testing strategies to tip the balance of power away from damaging processes and towards productive healing. The research program includes anti-inflammatory strategies, cellular therapies and gene therapies designed to harness the good part of the body’s response to spinal cord injury while limiting the bad parts of this natural response to injury.
What role does inflammation play in spinal cord injury?
Mechanical injury to the spinal cord is followed by an inflammatory response that leads to a great deal of damage that gets worse with time. However, inflammation also triggers processes such as wound healing that are of significant benefit. Most of the damaging effects of inflammation are carried out by a subset of white blood cells called neutrophils. In collaboration with the Weaver and Dekaban laboratories they are investigating the use of a monoclonal antibody that blocks these cells from entering the injured cord. This experimental treatment has shown remarkable success in preclinical animal studies and is being further developed.
Can stem cell transplantation be used to improve outcomes from spinal cord injury?
The capacity for repair in the injured spinal cord is greatly impaired because the mature central nervous system, with rare exceptions, is unable to generate new neurons or to regenerate axonal connections. Cell transplantation has therefore emerged as a promising treatment for spinal cord injury. They have investigated the use of adult stem cells derived from bone marrow in a mouse model of spinal cord injury. They have found that these stem cells promote repair of the spinal cord by promoting the repair and rescue of damaged tissue and by altering the expression of scar genes to promote regeneration.
Regeneration in the nervous system is hindered by the expression of genes that block nerve growth. What regulates the activation of these inhibitory genes?
The absence of axonal regeneration after spinal cord injury has been attributed to nerve-repelling molecules in the damaged myelin and scar. These inhibitory molecules in the scar are produced by reactive astrocytes responding to the injury. However, astrocytes have also been shown to produce molecules that promote nerve growth. We have identified a master control gene that regulates the balance between the anti- and pro-regenerative genes activated after spinal cord injury. They are currently devising strategies to block this master control gene so as to maximize the expression of pro-regenerative genes and minimize the expression of anti-regenerative genes after spinal cord injury.
Dr. Arthur Brown, a scientist at Robarts Research Institute at Western, received $782,455 from CIHR to study a protein (SOX9) he has identified that may control and promote regeneration in the injured spinal cord and alter scar gene expression after spinal cord injury.