Compound shows 'extraordinary' promise in restoring muscle function after spinal cord injury

Scientists have developed a new chemical compound that they say shows extraordinary promise in restoring muscle function in spinal cord injury patients.

The study, partly funded by the National Institutes of Health (NIH) and published in the journal Nature, used the compound intracellular sigma peptide (ISP), which was developed by Case Western Reserve scientists. It was used in 26 rats with severe spinal cord injury, and researchers recorded that the compound allowed paralyzed muscles to activate in more than 80 percent of subjects tested.

The team found that after seven weeks of daily injections, 21 of the rats regained the ability to urinate, move or both. Researchers noted the peptide allowed for nerve fibers to overcome scarring that normally blocked their regrowth, according to a news release.

“This recovery is unprecedented,” Jerry Silver, senior study author and Case Western Reserve University School of Medicine professor of neurosciences said in the news 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, especially bladder function,” he said.

When a spinal cord injury occurs, proteoglycans -- key components that play an important role in maintaining the structure of the nervous system – collect in the scar tissue at the injury site and in the perineuronal net.

Following the injury, proteoglycans become overly abundant in scar tissue and the impenetrable nets around synapses through the brain and spinal cord, which prevents regeneration, according to the news release.
The injury prevents the nerve fiber tips from traveling to the proper synaptic connections, which is what transmits information through electrical impulses to nerve cells that enable a person or animal to control bodily functions.

The scientists aimed for the ISP peptide to turn off the proteoglycan’s switch, and added a trans-activator of transcription to send the ISP through the nervous system and across cell membranes. The ISP penetrates the membranes of cells, including the scar tissue-covered injury site, according to the news release.

“There are currently no drug therapies available that improve the very limited natural recovery from spinal cord injuries that patients experience,” Lyn Jakeman, program director at NIH’s National Institute of Neurological Disorders and Stroke, said in the news release. “This is a great step toward identifying a novel agent for helping people recover.”

The team’s goal is to progress the ISP treatment forward so it can be used as a therapy following spinal cord injury. They are also exploring the possibility of using the compound to treat other disorders.

“ISP additionally has treatment potential for diseases where the body produces destructive scarring such as heart attack peripheral nerve injury and multiple sclerosis (MS),” Silver said.