Rats with spinal cord injuries have regained movement in their hindlimbs, as well as control of their bladder, with a newly developed drug that encourages nerve growth non-invasively. The findings were published in Nature last week.
Spinal cord injuries crush the axons of nerve cells, blocking the electrical signals between the brain and the body below the injury. According to previous studies, nerves don’t regrow across severed spinal cords because they’re repelled by inhibitory molecules released by the newly formed scar tissue. In normal, healthy tissue, these sugary proteins (called proteoglycans) are found in the matrix between cells, where they help maintain the structure of the nervous system. But after an injury, proteoglycans collect in scar tissue, and when they interact with a particular axon enzyme that’s found in axons (called PTP sigma), they form an impenetrable barrier (pictured below). This prevents nerve regrowth by producing a “sticky” trap that restricts the severed tips from journeying back to their proper synaptic connections.
By studying how the protein “glues” the tips of regenerating nerves to scar tissue, an international team led by Jerry Silver of Case Western Reserve University designed a molecular compound—called intracellular sigma peptide (ISP)—that basically sticks to that glue and allows nerves to regrow across the injured area. In addition to turning off the proteoglycan receptor, the team also added a molecular shuttle that sends ISP throughout the nervous system, including the scar-covered injury site.
The team tested various designs on neurons grown in petri dishes, and they found treatment with ISP freed axon growth. “It was amazing. The axons kept growing and growing,” Silver says in a National Institutes of Health statement.
Then over the course of seven weeks, the team gave daily ISP injections to 26 paralyzed rats suffering from severe spinal cord injuries. Eighty percent improved significantly: Their hindlimb paralysis disappeared or their coordination, balance, and urination improved. Some animals regained all of these functions while others got back one or two. “This recovery is unprecedented,” Silver says in a university release. “Each of the 21 animals got something back in terms of function. For any spinal cord-injured patient today, it would be considered extraordinary to regain even one of these functions.”
It’s a mystery why particular rats regained specific functions, though the answer may lie in the small amounts of nerve tracts that were spared in their spinal cords. One tract that responded well to ISP contains serotonergic fibers—which are responsible for releasing serotonin into the spinal cord, enhancing the function of the remaining nerve fiber tracts. Bleeding and inflammation damages these remaining tracts differentially, and their different serotonergic sprouting patterns might explain how different functions were regained. “Sprouting is a critical phenomenon,” Silver says. “Even if there are just a few intact fibers left after the injury, it could be one critical piece that brings back an important function.”
Images: Shutterstock.com (top), Silver lab, Case Western Reserve School of Medicine (middle)