The growth of nerve fibers is stimulated by sigma-peptide

The peptide restores the functions of the spinal cord

NanoNewsNet based on Case Western Reserve University materials
(Scientists design a peptide to promote functional recovery following spinal cord injury – VM).

Scientists from Case Western Reserve University have created a new chemical compound that demonstrates high efficiency in restoring functions lost as a result of spinal cord injury. This compound, called intracellular sigma peptide (ISP) by researchers, enabled activation of the function of paralyzed muscles in more than 80 percent of experimental animals. An interesting study, partially funded by the National Institutes of Health, was published in the journal Nature (Lang et al., Modulation of the proteoglycan receptor PTPsigma promotes recovery after spinal cord injury).

In this study, led by Jerry Silver, PhD, Professor of Neuroscience at the Case Western Reserve School of Medicine, 21 out of 26 experimental animals with spinal cord injury had their ability to urinate, move, or both restored. Apparently, the newly developed peptide allows nerve fibers to overcome the negative effects of scar formation, usually blocking their recovery.

This is an unprecedented recovery," Dr. Silver comments on the results. "Each of these animals had some kind of function restored. Today, for any patient with a spinal cord injury, restoring at least one of them, especially bladder function, would be something extraordinary. In addition, ISP has therapeutic potential for diseases in which destructive scars form in the body, such as heart attack, peripheral nerve injuries and multiple sclerosis."

Silver's group is now testing the effectiveness of ISP on animals with models of these diseases.

Immediately after injury to the central nervous system, molecules known as proteoglycans accumulate in the scar tissue at the site of injury and in the perineural network. In healthy tissue, proteoglycans are a key component of the intercellular matrix and play a leading role in maintaining the structure of the nervous system. However, after injury, there are too many proteoglycans in the scar tissue and impenetrable networks around synapses throughout the brain and spinal cord. The consequence of this is the formation of an insurmountable barrier that prevents regeneration and restoration of contacts between nerves. Proteoglycans form a viscous "swamp" that prevents the ends of severed nerve fibers (the so-called growth cones) from paving the way to their synaptic connections. It is through these connections that the most important information is transmitted through electrical impulses to nerve cells that allow a person or an animal to control key functions of the body.

The ISP peptide developed by the researchers switches the "toggle switch" of the neural receptor of proteoglycans to the "off" position. In addition, the researchers added to it a "shuttle" molecule called trans-activator of transcription (TAT), which promotes the spread of ISP throughout the nervous system and its passage through cell membranes, including the scar tissue-covered injury site. Since peptides are able to pass through tissue, ISP can be administered systemically rather than into the spinal cord.

Scientists have developed a drug that allows axons to overcome the barrier of scar tissue,
blocking the restoration of nerve fibers (photo: Silver lab)

"Our treatment strategy is designed so that it can be easily applied in practice," says Bradley Lang, a graduate student in Silver's lab and lead author of the study. "Our goal is to refine this method for use as therapy after spinal cord injury."

In this study, 26 rats with severe spinal cord injuries received daily ISP injections for seven weeks. All this time, scientists evaluated their ability to walk and maintain balance and controlled when and how much they urinated. The results showed that 21 of the 26 animals recovered one or more functions. Some animals recovered all three functions, others – one or two of the three.

"We don't know why a particular animal has recovered a certain function," Dr. Silver admits. "This is one of the main remaining issues."

One explanation for such results may be a small number of neural pathways preserved in the spinal cord of animals. These remaining pathways are damaged to varying degrees by bleeding or inflammation that persists after the initial injury. One particularly important pathway that responded strongly to ISP contains serotonergic fibers. These fibers secrete the neurotransmitter serotonin into the spinal cord, which, in turn, significantly increases the functional activity of a limited number of remaining fibers that control subsequently restored functions.

All animals had different patterns of springing (germination) of serotonergic nerve fibers and a different degree of preservation of nerve pathways, which probably explains the difference in restored functions.

"Sprutting is the most important phenomenon," Silver emphasizes. "Even if only a few intact fibers remain after the injury, they can become the crucial element that will return some important function."

"Currently, there are no drugs available that would improve very limited natural recovery after spinal cord injury," Lyn Jakeman, director of one of the programs of the National Institute of Neurological Disorders and Stroke (NIH), commented on the study of Silver's group. "This is a big step forward in finding a new agent to help people recover."

Portal "Eternal youth" http://vechnayamolodost.ru08.12.2014