Jerry Silver (Case Western Reserve University)
4 December 2014. Researchers at Case Western Reserve University developed a synthetic peptide that in lab animals restores some functions in muscles damaged from spinal cord injuries. The team from the lab of CWRU neuroscientist Jerry Silver in Cleveland, Ohio published its findings yesterday in the journal Nature (paid subscription required). National Institute of Neurological Disorders and Stroke, part of National Institutes of Health, funded some of the research, and the university filed a patent application for the synthetic peptide.
Silver and colleagues — from CWRU, Ohio State, Johns Hopkins, Temple University, Baldwin-Wallace University, and University of Manitoba — were seeking a way of restoring muscle functions of patients with spinal cord injuries. In these cases, injuries to the spinal cord result in scar tissue with a build-up of carbohydrates known as chondroitin sulphate proteoglycans.
While proteoglycans play a key role in making tissue between cells in the body, after a spinal cord injury the accumulation of chondroitin sulphate proteoglycans creates an impenetrable barrier that prevents regeneration of new nerve cell connections. Without these connections, the brain and spinal cord cannot send or receive signals with various muscles involved in basic bodily functions.
The researchers investigated ways of reaching receptor proteins for chondroitin sulphate proteoglycans that can limit their effects on muscles, and thus restore their ability to receive brain signals, while avoiding the injury to the spinal cord. Earlier studies identifed a potential culprit: protein tyrosine phosphatase sigma, an enzyme in nerve fibers that interacts with chondroitin sulphate proteoglycans to cut the nerve fibers and create the barrier.
The team, led by then-doctoral candidate Bradley Lang, designed a synthetic compound called intracellular sigma peptide that penetrates the scar tissue as well as the cell membranes at the injury site and binds to protein tyrosine phosphatase sigma, which limits the enzyme’s effects. This binding action, along with a mechanism to shuttle serotonin, a neurotransmitter chemical, between the nerve cells and muscles reconnects signals between the brain and muscles, enabling the regeneration of nerve fibers and recovery of some muscle function.
The researchers tested intracellular sigma peptide in lab rats paralyzed from spinal cord injuries. Of 26 animals in the study, 21 recovered walking, balance, or bladder functions after daily injections of intracellular sigma peptide over 7 weeks. Injections were delivered under the animals’ skin, and thus do not disturb the spinal cord injury. Similar placebo injections had no effect.
Inspection of the spinal cords showed new nerve fibers grow below the site of the injury. In addition, muscle recovery varies among the animals, which the team suggests may be due to the nature and amount of damage from the original injury.
“Our goal,” says Silver in a university statement, “is to progress this treatment forward for use as a therapeutic following spinal cord injury.” Silver believes that the technology can also be applied to other types of damage from scarring, such as heart attacks, peripheral nerve injury, and multiple sclerosis.
Silver and Lang tell more about the study in the following video.
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