Why is Interferon-Beta Treatment Ineffective for Some with MS?
The common multiple sclerosis treatment, according to a study out of Duke, may do very little for as many as half of people with the disease. In a mouse model of MS, they identified different disease pathways in those resistant to the treatment, raising questions about the heterogeneity of MS.
Alleging that as many as half of those who suffer from multiple sclerosis (MS) may not respond to one of the most common medications used to slow its progression, researchers from Duke University sought to find out why, and what treatments they perhaps would find success with. The study was published this November in Nature Neuroscience.
Interferon-beta treatments, which include Biogen’s Avonex and Merck’s Rebif, has shown effectiveness in a number of studies, though it carries a litany of potential side effects, including flu-like symptoms. It’s expensive, however, and for many patients it simply doesn’t do much, perhaps because there isn’t one single uniform variety of MS.
To understand the mechanisms at play, the Duke researchers used mice with experimental autoimmune encephalomyelitis, an animal model of the disease. They found what lead author Mari Shinohara called “a really clear molecular mechanism that may explain why some people do not respond to interferon-beta treatment.”
MS is, in a sense, a struggle between the body’s immune and neurological systems, in which the immune system mistakenly attacks the protection of the nerves and causes a variety of signaling problems. In a previous 2012 study of mice, Shinohara and company determined that interferon-beta treatment only worked when the disease was dependent on NLRP3 inflammasome, a protein complex that the researchers believe was responsible for triggering the immune system’s faulty attacks.
Interferon-beta targets NLRP3, which is what makes it an effective treatment for many. In the same study, however, the team noticed that some mice in whom interferon-beta was ineffective were without the inflammasome, but still showed signs of the disease. The goal in the new study was to figure out why.
They found two receptors, CXCR2 and LTBR, that were active in those mice nonresponsive to interferon-beta, and also identified a molecule that could block them. “We found that, depending on which type of disease the mice had, we could choose the appropriate treatment,” said Shinohara.
In an effort to make these findings applicable to humans, they used data from the ongoing Murdock MS study. Examining the genetic expressions of the patients in whom interferon-beta was not effective, they found CXCR2 and LTBR production to be upregulated.
“This new model gives us opportunities to explore a different disease mechanism that has been elusive to the field thus far,” said Dr. Xiaoxia Li of the Cleveland Clinic, a researcher not involved in the study. “I believe it will have a large impact on both the basic and translational research on multiple sclerosis.”
The study places its findings among research that “may provide new molecular insights in developing prognostic indicators and treatments of MS as a heterogeneous disease.”
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