“Extraordinary promise” has been shown in a new chemical compound, claim researchers, who report that it activated paralyzed muscles in more than 80% of animals in trials.
An international team of scientists were involved in the research, during which 21 of 26 animals with spinal cord injuries regained the ability to urinate or move, or both, following treatment with intracellular sigma peptide (ISP).
Lyn Jakeman, PhD, a program director at the National Institute of Neurological Disorders and Stroke in Bethesda, MD, explains that there are currently no drug therapies available “that improve the very limited recovery from spinal cord injuries that patients experience.”
As such, Jakeman says the new treatment is “a great step toward identifying a novel agent for helping people recover.”
The results of the study are published in the journal Nature.
Lead author Jerry Silver, PhD, Case Western Reserve University School of Medicine professor of Neurosciences, explains the findings:
“This recovery is unprecedented. 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. ISP additionally has treatment potential for diseases where the body produces destructive scarring such as heart attack, peripheral nerve injury and multiple sclerosis (MS).”
Proteoglycans – key molecules that maintain the structure of the central nervous system (CNS) – gather in scar tissue at the site of any injury to the CNS. Though important and beneficial in healthy tissue, proteoglycans become overabundant in scar tissue and around synapses and the spinal cord.
This overabundance results in sticky barriers that prevent the electrical impulses being transmitted to nerve cells that would ordinarily allow bodily functions to be controlled.
The ISP peptide was designed to switch off proteoglycan receptors in neurons. A “shuttle” – called TAT, or trans-activator of transcription – was also developed that would allow ISP to travel across membranes and throughout the CNS.
This ability to cross membranes means that ISP can easily pass through the scar tissue of injury sites. It also allows the compound to be delivered systematically rather than through a direct spinal cord injection.
The compound was trialled on 26 rats with severe spinal cord injuries, all of whom were assessed of their abilities to walk, balance and urinate. Although some rats regained all of these functions, some of them only regained one or two. Overall, 21 of the 26 rats regained some – if not all – function.
Although the researchers do not know why some of the rats recovered completely and others did not – “That is one of the big remaining questions,” says Silver – they think a clue may be found in the nerve tracts of the rats’ spinal cords.
Each rat had different damage to their spinal cord tracts. However, one spinal cord tract in particular – which contains serotonergic fibers that release serotonin into the spinal cord – was shown to respond strongly to ISP.
Because both the levels of damage and the sprouting patterns of serotonergic fibers were different in each rat, factors affecting this tract may account for the variations in regained behaviors. Silver explains:
“Sprouting is a critical phenomenon. 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.”
The team will continue to investigate. “Our goal is to progress this treatment forward for use as a therapeutic following spinal cord injury,” Silver says.