On April 2, The Journal of Neuroscience published a study on the use of a single administration of a gene-therapy targeting scar tissue at the site of a spinal cord injury in rats. The gene therapy helped nerve cells survive, and improved function of the affected hind limbs over the course of weeks, raising the possibility that the therapy might be useful to treat humans with spinal cord injuries.
Spinal cord injury is one of the most intractable medical problems, affecting, as it does, the main conduit for sensory and motor information from the brain to the body and back. When the spinal cord is injured, scar tissue forms, inhibiting re-growth of the axonal processes that make up the nerve cord.
In previous studies in animal models, an enzyme called “chondroitinase ABC” (ChABC) has been applied to the point of the injury – this enzyme digests the proteins that form scars and promotes growth of injured spinal neurons. Unfortunately, however, the enzyme is delicate and quickly broken down, and thus has to be administered repeatedly. Since injecting anything into the spinal cord repeatedly is invasive and dangerous, scientists have begun to look at the prospect of changing spinal nerves genetically to put out their own ChABC. Because the therapeutic enzyme is by nature a protein, it is a fairly simple matter to create a gene that codes for production of the ChABC.
In the study reported on today, researchers at King’s College London led by Elizabeth Bradbury, PhD, introduced a gene for ChABC directly into the neurons of the spinal cord in injured rats. The treated spinal cord cells then produced and secreted large amounts of their own ChABC all over the site of the injury; the gene therapy also helped maintain the health of the injured spinal cord, improving hind limb function in the treated rats within 12 weeks to the point where they were able to negotiate a horizontal ladder. Additionally the ChABC gene therapy altered the response of inflammatory cells at the site of the injury. Under usual circumstances, after an injury, immune cells enter the spinal cord, causing irreparable tissue damage. However, the ChABC gene therapy diminished the number of the destructive immune cells and caused an increase in the presence of different immune cells (M2 macrophages) that reduce inflammation and enhance tissue repair. Other scientists hailed the findings, calling the evidence for successful gene therapy with chondroitinase “convincing,” and suggesting that the study could lead to testing similar therapies in people with spinal cord injuries.
Spinal cord injuries afflict primarily young adults between age 16 and 30; approximately 273,000 persons are estimated to be living with spinal cord injuries as of 2013. The annual incidence of spinal cord injury in the US (not including fatalities), is about 40 cases per million or nearly 12,000 new cases every year. According to a publication put out by the University of Alabama at Birmingham, the yearly costs associated with living expenses and health care and the estimated lifetime costs directly attributable to spinal cord injury are staggering, and vary with severity and age of injury. Incomplete motor function at any level costs approximately $340,787 for the first year, and $41,393 every year thereafter. Estimated lifetime cost for a person injured at age 25 is $1,547,858 or $1,092,521 if the injury happens at age 50. Even a moderate advance in the recovery of a person with spinal cord injury would be of great economic benefit. As the lead researcher of the current study pointed out, their ability to deliver the gene therapy to the site of injury that persists in large areas of the spinal cord and improves limb function in animal models will be “important” for translating the therapy into clinical research on humans.
By Laura Prendergast
University of Alabama, Birmingham