Peter Calabresi has been studying multiple sclerosis for over 30 years. As a young neurologist-in-training, he decided to specialize in the autoimmune condition because it struck him as a “particularly cruel disease.”
People usually receive their diagnosis when they’re young adults. A healthy lifestyle can help with symptoms, but won’t prevent the disease. And it’s incurable.
There have been significant advancements in treatments to help patients manage the disorder in recent years, particularly when it comes to relapsing-remitting MS, the form of the disease that involves symptom flare-ups followed by periods of remission. But one iteration of the disease — progressive MS, which is characterized by a steady decline in function — has proved particularly stubborn to find therapies for.
A new study conducted by Calabresi, however, published in Nature Neuroscience earlier this year, holds clues to potential treatments.
Calabresi, the chair of the Department of Neurological Sciences at the Robert Larner College of Medicine at the University of Vermont, cautions that he is not “on the brink of a cure.” But he said the five-year research effort, which studied how brain cells die in response to MS-induced inflammation, is nevertheless “really exciting.”
“It addresses this huge need in the field to understand the mechanisms that underlie progressive MS,” he said.
Nearly one million adults have multiple sclerosis in the U.S., although the disease is most prevalent in the Northeast. UVM’s multiple sclerosis center serves about 1,500 patients across Vermont, New York and New Hampshire. The autoimmune disorder is roughly three times more common in women than men.
The disease causes immune cells in the blood to mistakenly attack myelin, the protective covering that surrounds nerves. These attacks cause inflammation and lesions on the spinal cord and brain, interrupting communication between the brain and the body. Symptoms include muscle weakness, numbness, fatigue and problems with balance and vision as well as impaired cognition.
Drugs do exist to help block the immune system from further attacking myelin, but lesions that developed before treatment started don’t go away and cause chronic inflammation in the brain.
“That slowly makes people worse, and often after 20 years, people will progress and become disabled and we really need to develop better therapies for that,” Calabresi said.
So Calabresi’s team switched from studying the immune cells and instead began investigating why inflammation was causing certain brain cells to die.
Borrowing from research into Parkinson’s disease, they decided to investigate a molecular process that leads to cell death called parthanatos and found that it was also taking place in cells from people with MS. They also found they could block the process with drugs and gene therapy.
There’s still a lot of work to do before this can result in real-world treatments, said Calabresi. His lab will have to replicate their findings at different points in disease progression and work with chemists to develop compounds that can both cross the blood-brain barrier and be safe for long-term use. If they find such compounds, they’ll then have to run clinical trials. But he’s optimistic.
“I hope someday from now, we'll look back and say that maybe this was a pivotal moment,” he said.
