Gene Therapy for Spinal Cord Injury


    After a devastating spinal cord injury the most important thing a paralyzed person wants to gain back is control of their hands. It is not so much about recovery of the legs or the recovery of a walking gait. Wheel chairs and exoskeletons can already support that function. What patients really want is to return to independence. That fine motor control that allows your opposable thumbs to move, to dress yourself, to do up buttons, to pick up a knife and fork, to twist a door knob - that is what gives people hope for independence. To that end scientists working in the nerve regeneration field have sought for decades to help patients recover their hand function and forearm motion.

    Last week, a team from my alma mater, King's College London, published a report in Brain detailing the use of gene therapy to promote functional recovery of forehand motion in paralyzed rats. They reported that rats could recover the use of their forepaws to pick up sugar cubes after a contusion spinal injury. The spinal cord is made up of densely bundled nerves carrying messages from the brain to the rest of the body. Injuries to the spinal cord result in two principle barriers that prevent axon regeneration and recovery. First is the scar tissue that forms immediately after injury, made of chondroitin sulfate proteoglycans that wrap around the damaged area. Second is the inflammatory response that lasts from weeks to months and comes into play as part of the body's repair system. This gene therapy being tested is a new lentivirus that encodes chondroitin sulfate proteoglycans ABC (ChABC), an enzyme that digests the scar tissue. The lentivirus is regulated by an inducible vector system made up of two plasmid components: one is the doxycycline-inducible ChABC vector system, where upon addition of Doxycycline, ChABC can be activated. The second vector is the GARrTA transactivator vector which helps the ChABC vector system activate without causing a T-cell mediated immune response. The researchers in this report have named it dox-i-ChABC. and claim to see positive effects in rat models in as little as 2.5 weeks of applying the gene therapy. The report in Brain showed improvements in behavioral assessments of rat forepaw function as well as evidence of increased activity in the sensory and motorneuron tracts along the spinal cord after treatment.

    This group, led by Professor Elizabeth Bradbury, has for many years championed the use of ChABC as a way to stimuate damaged axons to re-grow. The latest iteration of delivering ChABC into the contused spinal cord in this two-vector lentivirus system is an exciting one. However, spinal cord injury and paralysis is not a disease that lends itself well to gene therapy. It is not a monogenic disorder. Axon growth requires a multiplicity of factors to be in place and a multi-pronged approach will be needed for human treatment. It will be interesting to see whether this gene therapy makes it to early clinical trials.