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Studies suggest that promising MS drugs can exacerbate the disease

Studies suggest that promising MS drugs can exacerbate the disease

 


Drugs that have shown promising treatments for multiple sclerosis can actually exacerbate debilitating illness, a new study from the University of Virginia School of Medicine suggests.

The drug has not yet been tested on humans in MS, but UVA scientists warn fellow researchers to proceed very carefully. In addition to exacerbating the disease in the mouse model, they report that the drug also had unintended, untargeted effects.

“That wasn’t what we expected,” said Dr. Alban Gaultier, an MS researcher at UVA’s Department of Neuroscience and its Brain Immunology and Glia Center (BIG). “The message of take-out is that we need to be very careful and do more basic research before we propose to bring it into clinical trials.”

About multiple sclerosis

Multiple sclerosis is a debilitating autoimmune disease that affects an estimated 1 million Americans. The disease causes the body’s immune system to destroy myelin, the insulator that surrounds and protects our nerve fibers. This prevents nerves from sending signals to the brain. Injuries can cause a variety of symptoms, including muscle spasms, malaise, difficulty moving, numbness, and pain. These symptoms vary from patient to patient.

Because existing multiple sclerosis drugs have unwanted side effects, such as impairing the body’s ability to fight infections, doctors are keen to develop better alternatives. One of the promising candidates is a small molecule drug called TEPP-46. Originally developed to combat cancer, TEPP-46 targets what is known as “metabolic adaptation” (a change in the way cells generate energy) that occurs in both cancer and multiple sclerosis. I will.

However, in Gaultier’s MS model, TEPP-46 exacerbated the disease and redirected inflammation from the spinal cord to the brain. He and his team do not fully understand why, but he and his collaborators have determined that the drug has caused harmful changes in immune cells called T cells. There was also an unexpected “off-target” effect. This means that the drug affected cellular processes other than intended.

Gaultier said his findings were in conflict with other studies and that further research was needed before scientists could transfer the drug to clinical trials in people with multiple sclerosis. ..

One of the benefits of the new study suggests that TEPP-46 could be used to create better mouse models of MS and help scientists understand and treat the disease. That is.

“It’s something that could be very helpful,” Gaultier said. “In this animal model of MS, most of the inflammation occurs in the spinal cord, so the drug could be used to reprogram immune cells to transfer the condition from the spinal cord to the brain. It better mimics human illness. “

Published survey results

Researchers have published their findings in the scientific journal Science Signaling. The research team consists of Scott M. Seki, Copper Posenic, Rebecca McCloud, Dorian A Rosen, Anthony Fernandez Casstan Eda, Rebecca M. Baiter, Vlad Selbrea, Sarah C. Nanjiri, Nicholas Hayes, Charles Spivey, and Relisa Gemta. it was done. , Timothy Block, Old Dragon Sue, Gaultier.

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