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A drug that has shown promise for treating multiple sclerosis could actually worsen the debilitating disease, new research from the University of Virginia School of Medicine suggests.
The drug has not yet made it to human trials for MS, but UVA scientists are warning their fellow researchers to proceed with extreme caution. In addition to worsening the disease in mouse models, the drug also had unwanted and off-target effects, they report.
“It wasn’t at all what we expected,” said MS researcher Alban Gaultier, PhD, of the UVA Department of Neuroscience and its Center for Brain and Glia Immunology (BIG). “The take-home message is that we should be very careful and do more fundamental research before we propose to take this to clinical trials.”
Information on multiple sclerosis
Multiple sclerosis is a debilitating autoimmune disease that affects approximately 1 million Americans. The disease causes the body’s immune system to destroy myelin, the insulation that surrounds and protects our nerve fibers. This prevents the nerves from transmitting signals to the brain. The damage can create a wide range of symptoms, including muscle spasms, fatigue, difficulty moving, numbness, and pain. These symptoms can vary from patient to patient.
Existing MS medications carry unwanted side effects, such as impairing the body’s ability to fight infections, so doctors are eager to develop better alternatives. A promising candidate is a small molecule drug called TEPP-46. Originally developed to fight cancer, TEPP-46 targets what is known as “metabolic adaptation” – changes in the way cells generate energy – which occurs in both cancer and MS.
In Gaultier’s MS models, however, TEPP-46 worsened the disease by redirecting inflammation from the spinal cord to the brain. He and his collaborators determined that the drug caused harmful changes in immune cells called T cells, although he and his team don’t fully understand why. There were also unexpected “off target” effects, meaning the drug affected other cellular processes than expected.
Gaultier notes that his findings contrast with other studies and says more research is needed before scientists move the drug into clinical trials in people with MS.
A positive aspect of the new research is that it suggests that TEPP-46 could be used to create better mouse models of MS, helping scientists in their efforts to understand and treat the disease.
“It’s something that could be very useful,” Gaultier said. “In this animal model of MS, most of the inflammation takes place in the spinal cord. So by using that drug and reprogramming the immune cells, we were able to move the disease from the spinal cord to the brain, which better mimics the disease. Human . “
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Materials provided by University of Virginia Health System. Note: The content can be changed by style and length.
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