New research from the US suggests there may be two types of multiple sclerosis, each with a different response to beta-interferon, the main drug used to treat the disease.
You can read about the study, led by researchers at Stanford University School of Medicine, online in the 28 March issue of Nature Medicine.
The National Multiple Sclerosis Society in the US estimates there are some 400,000 Americans living with the disease.
Nobody quite knows what triggers it, but multiple sclerosis occurs when the immune system’s T cells attack the myelin sheath that surrounds the long wirelike projections that allow nerve cells in the brains and peripheral tissue of mammals to transmit electrochemical impulses to other nerve or muscle cells, often over long distances.
Destruction of the myelin sheath, which preserves the strength and even accelerates the speed of the signals, leads to symptoms of multiple sclerosis, including, eventually, paralysis and blindness.
Using mice and blood samples from humans, senior author Dr Lawrence Steinman, who is the George A Zimmerman Professor of Neurology and Neurological Sciences at the Stanford University School of Medicine, and colleagues, found there are probably two kinds of multiple sclerosis and suggests that a patient’s response to beta-interferon, the first line drug for treating this episodic and often recurring autoimmune disease, appears to depend on which version he or she has.
In a statement, Steinman said that if the findings are confirmed by other labs doing larger studies in humans, people with multiple sclerosis might one day be able to take a simple blood test to find out whether they are likely to respond to the standard treatment.
This would likely also save a lot of money, said Steinman, since beta-interferon is an expensive bio-engineered drug with annual global sales of around 4 billion dollars a year.
Steinman described the drug’s effectiveness as “fair”: only half of patients experience any benefit, and when they do it only reduces on average a third of recurrences.
Also, because the drug doesn’t always work, and it has uncomfortable side effects (like having the flu), patients don’t always take it as they should.
For the study, Steinman and colleagues used laboratory mice that had been injected with myelin in such a way that it caused their immune systems to attack their own myelin coating around their nerve cells, thus inducing a form of multiple sclerosis that is called experimental autoimmune encephalitis (EAE).
They found however that EAE can be induced via two different pathways, depending on how the T cells are activated. What activates them is a type of signalling molecule called a cytokine, of which two types, gamma-interferon and IL-17, typically cause T cells to produce the sort of inflammations that can trigger multiple sclerosis.
First author Dr Robert Axtell, now a postdoctoral scholar in Steinman’s lab, had worked with EAE mice while working towards his PhD at the University of Alabama. For this study, he, Steinman and the rest of the team, induced two superficially different types of EAE by getting the T cells that attacked the myelin to secrete mainly gamma-interferon or IL-17.
They found that when they gave beta-interferon to the mice whose EAE had been induced by T cells secreting mainly gamma-interferon, their condition improved, but it made the symptoms worse in the mice whose EAE was brought on by T cells secreting mainly IL-17.
In the next phase of the study, they turned to humans. Second author Dr Brigit deJong, another postdoctoral scholar in Steinman’s lab, had previously done some work in Amsterdam where researchers had closely followed multiple sclerosis patients treated with beta-interferon. The team on this study got hold of 26 blood samples that had been taken from those patients both before and then two years after the treatment started.
They found a pattern in the IL-17 levels in the samples where a type of of IL-17 called IL-17F was either very high or very low.
When they compared this to information about the patients’ response to treatment (the researchers who did the IL-17F analysis did not know about the treatment outcomes until after they had done the analysis), they found that the patients who had very low levels had responded well to beta-interferon treatment, ie they had no relapses and no episodes requiring steroids to quickly shut down a malfunctioning immune system.
But the patients whose blood samples contained very high levels of IL-17F (about one third of the total patients) responded poorly to the beta-interferon treatment, by the same criteria. In fact, said Steinman, the evidence suggests it may even have made their condition worse.
The researchers warned that these results should now be confirmed by larger studies with more patients. However, Steinman told the media:
“I think this has the potential to transform the way we take care of people with multiple sclerosis.”
By this he meant two things: first, as already mentioned, the discovery might lead to a simple blood test that could save many patients the heartache of undergoing a treatment that won’t help them, plus save money; and second, is that we might discover that beta-interferon is actually quite effective when given only to the patients who are predisposed to respond to it.
“T helper type 1 and 17 cells determine efficacy of interferon-β in multiple sclerosis and experimental encephalomyelitis.”
Robert C Axtell, Brigit A de Jong, Katia Boniface, Laura F van der Voort, Roopa Bhat, Patrizia De Sarno, Rodrigo Naves, May Han, Franklin Zhong, Jim G Castellanos, Robert Mair, Athena Christakos, Ilan Kolkowitz, Liat Katz, Joep Killestein, Chris H Polman, René de Waal Malefyt, Lawrence Steinman and Chander Raman.
DOI:10.1038/nm.2110
Source: Stanford University School of Medicine.
Written by: Catharine Paddock, PhD