New Multiple Sclerosis Treatment in Development
Successfully treating and reversing the effects of multiple sclerosis (MS) may one day be possible using a drug originally developed to treat chronic pain, according to Linda Watkins, PhD, of the University of Colorado at Boulder.
Dr. Watkins and her colleagues in the Department of Psychology and Neuroscience found that a single injection of the compound ATL313—an anti-inflammatory drug being developed to treat chronic pain—stopped the progression of MS-caused paralysis in rats for weeks at a time.
“What happens now with MS drugs is they slow or stop the progression of MS, but they don’t treat it,” Dr. Watkins said. “They don’t take people back to normal, because the lesions caused by MS don’t heal.”
The researchers hope to use spinal cord and brain-imaging technology to extend their studies to determine if lesions are being healed in rats that received an ATL313 injection. “If we have a drug that is able to heal these lesions, this treatment could be a major breakthrough in how we treat the symptoms of MS in the future,” she said.
The new findings were surprising, noted Dr. Watkins. The team had originally wanted to look at the drug’s potential in treating pain associated with MS, because about 70% to 80% of patients with MS have chronic pain that is not treatable.
“What we had originally thought about this class of compounds is that they would calm down glial cells in the spinal cord, because their pro-inflammatory activation is what causes pain,” she said.
Under normal circumstances, glial cells are thought to be like housekeepers in the nervous system, Dr. Watkins noted, essentially cleaning up debris and providing support for neurons. Recent work by Dr. Watkins and others has shown that glial cells in the CNS also act as key players in pain enhancement by exciting neurons that transmit pain signals.
“What’s become evident is that glial cells have a Dr. Jekyll and Mr. Hyde personality,” Dr. Watkins said. “Under normal circumstances, they do all these really good things for the neurons, but when they shift into the Mr. Hyde formation they release a whole host of chemicals that cause problems like neuropathic pain and other chronic pain conditions.”
The researchers found that ATL313 appears to reset the glial cells from an “angry” activated state to a calm anti-inflammatory state that may heal MS lesions.
A New Way to Enhance Neuron Repair in Spinal Cord Injury?
If researchers could determine how to send signals to cells responding to a spinal cord injury, they might be able to stop one type of cell from doing additional damage at the injury site and, instead, coax it into helping nerve cells grow.
That is the theory behind new research at Ohio State University, where investigators are trying to determine how to simultaneously stop damage and promote neuron growth with a single, targeted signal. The cells in question are macrophages. After a spinal cord injury, macrophages travel to the injury site from at least three known locations in the body as part of an intense infl amatory response. After several days, these cells promote inflammation and toxicity, which can exacerbate effects of the original injury. But these same cells might also offer hope for restoration of function in people with injured spinal cords.
Investigators previously found that macrophages receive signals at the site of a spinal cord injury that cause them to both promote the growth of axons and cause tissue damage. The new study suggests that there could be a way to manipulate these signals to silence the damaging effects while enhancing the repair function.
“We know a single population of macrophages has both capabilities,” said John Gensel, a postdoctoral researcher in neuroscience at Ohio State University and lead author. “But we’ve also found that there are some specific receptors we can target that reduce the pathologic potential of macrophages while retaining their regenerative characteristics.”
The researchers consider manipulation of the immune response after spinal cord injury a potential therapy approach for these devastating traumas, for which no federally approved treatments currently exist.
Using a synthetic molecule to stimulate macrophages, the group previously showed that multiple receptors on these cells were involved in their activation, and that the receptors dictate how the macrophages behave. If more than one receptor is stimulated, the macrophage has the potential to either kill a nerve cell, stimulate it to grow, or both.
“What we’re trying to do is split the activation switch, so there could be two switches, and you can keep one off and turn the other one on,” said coauthor Phillip Popovich, PhD, Professor of Neuroscience and Director of Ohio State’s Center for Brain and Spinal Cord Repair. “We think we have learned how to do that, at least with regard to one signaling pathway.”