Stanford researchers published findings on Sunday indicating that there are two types of multiple sclerosis (MS) that respond differently to the most common drugs used today. These findings could have clinical applications for personalizing the current treatments for MS.
MS is an autoimmune disease in which T-cells attack the myelin sheaths surrounding neurons, causing loss of nerve function over time. The disease affects 400,000 people in the United States and 2.5 million worldwide.
Beta-interferon is one of the most popular treatments for MS. It has not, however, been uniformly effective. Almost a third of users suffer from intense flu-like side effects that for some are intolerable, and some patients do not improve with the treatment.
Stanford researchers led by Lawrence Steinman, a professor of neurology and neurological sciences at the School of Medicine, wanted to find out why.
The study, published in Nature Medicine, used mouse models of MS to examine the effects of beta-interferon on two different T-cell models. Steinman discovered that beta-interferon improves the conditions of mice whose MS was caused by gamma-interferon-producing T-cells. However, it worsens the condition of mice whose MS is caused by IL-17-producing T-cells.
To determine whether or not the findings in the mouse model might be the same in humans, blood samples from 26 patients were sent to Stanford from collaborators in Amsterdam. The researchers, unaware of which patients responded to beta-interferon, screened the blood for levels of IL-17.
“[The results] were completely congruent with what we saw in the mouse [model],” Steinman said.
Indeed, those patients with elevated IL-17 levels responded poorly to beta-interferon therapy.
The findings point to two different types of MS: one caused by Type 1 T-cells that secrete gamma-interferon, and one caused by Type 17 T-cells that secrete IL-17.
Beta-interferon is an effective therapy for gamma-interferon MS, but not for IL-17-induced MS. A simple blood test could determine the patient’s type of MS, based on the level of IL-17 present.
“[The blood test] could be done as soon as we validate [the findings] in a larger cohort,” Steinman said. “Once validated, the test is very straightforward; it could be implemented quite easily.”
Steinman plans to continue with a large cohort study to validate the results found in the mouse model and initial human screening. If the large group study supports these findings, the blood test for IL-17 could be used to determine a patient’s course of treatment and maximize the likelihood that the prescribed drug would control their MS.
“I think this has the potential to transform the way we take care of people with multiple sclerosis,” Steinman said in a news release. “The other side of the coin is that beta-interferon, if it’s given only to those who are predisposed to respond to it, could turn out to be a far better drug than we ever imagined.”
Beta-interferon could be administered in a less diluted form to those patients who are predisposed to respond well. In addition, a different drug called Copaxone could be administered to those patients with high IL-17.
“[It] turns out we know where Copaxone will work best as well . . . but we haven’t published it yet,” Steinman said.
These findings could lead to a more personalized treatment process for MS, beginning with a blood test before drugs are prescribed. Steinman plans to pursue future possibilities for simple tests to improve treatment — both for MS and other diseases.
“In the future [we] should do a test before we just prescribe something,” Steinman said. “There needs to be a lot more money being spent on figuring these things out.”
In addition, these findings could help to better allocate money spent on MS prescription drugs. Currently, beta-interferon is made by four different companies and is a $4 billion industry. Copaxone production is also a $3 billion industry.
By personalizing drug treatment, Steinman pointed out that money could be saved on ineffective prescription of drugs and in treatment of their unnecessary side effects.
The study was co-authored by many other Stanford researchers, researchers from the University of Alabama at Birmingham and researchers in the Netherlands.