Many new treatments for multiple sclerosis (MS), an autoimmune disease attacking the central nervous system, have been developed within the last ten years. But sometimes these drugs aren’t effective for certain people or have side effects or are difficult to administer. Scientists continue to look for better drugs and therapies as well as ways to eliminate MS. Below is a research update on a variety of studies that BRI is conducting or collaborating on with other institutions. They are tackling various scientific and immunologic questions that explore innovative ways to fight MS from the lab to clinical studies.
CAN AGGRESSIVE THERAPY HALT AGGRESSIVE MS?
In a clinical trial led by the Immune Tolerance Network (ITN), researchers used high-dose chemotherapy to suppress the immune system and transplanted the participants’ own stem cells to see if they could induce sustained remission in early aggressive relapsing-remitting MS. This year, the three-year interim report showed the approach to be highly effective. For this clinical trial, called HALT-MS, the ITN team at BRI leads a large multi-institutional research effort. At BRI, William Kwok, PhD, is researching the molecular details that describe immune responses in participants in this trial study.
CAN ABATACEPT STOP OR DELAY THE PROGRESSION OF MS?
The science behind abatacept is different from other approved treatments for MS. Unlike most immunosuppressive drugs, abatacept targets a specific molecule on the surface of T cells that leads to changes in cell activation. T cells are key players in the autoimmune attack that leads to disability in MS. Because abatacept affects the immune system in a more specific way, researchers are evaluating its potential as a treatment for MS with fewer side effects than current medications. This study, called ACCLAIM, is being conducted by the ITN. BRI clinical researcher Mariko Kita, MD, enrolled patients in the study, and BRI scientists Adam Lacy-Hulbert, PhD, Jessica Hamerman, PhD, Estelle Bettelli, PhD, Dan Campbell, PhD, Steve Ziegler, PhD, and Jane Buckner, MD, are analyzing the immune system response of participants in the study.
ORAL THERAPIES ARE AVAILABLE, BUT ARE WE USING THE RIGHT DOSE?
The last five years has seen the introduction of oral therapies to treat MS. Clinical researchers are examining whether the current dosing regimens are optimal and are comparing the effectiveness of two different doses of an oral drug (fingolimod) with an injectable drug (glatiramer acetate) at reducing relapses associated with relapsing-remitting MS (RRMS). Patients with RRMS have recurrent acute episodes (relapses) of neurological symptoms that are followed by a complete or partial recovery. It is hoped that reducing the number of relapses may help slow the progression of the disease. Achieving the optimal dosing schedule will help to individualize care of patients with MS. Dr. Kita is currently enrolling patients in this study.
HOW DO SOME MS DRUGS WORK AT A MOLECULAR LEVEL?
Dr. Bettelli, PhD, in collaboration with Mohamed Oukka, PhD, Seattle Children’s Research Institute, has been developing new experimental models to understand how the oral drug fingolimod works at a molecular level and how it is modulating different cells of the immune system. Does the drug work differently in different people and on different immune cells? Eventually this information will help clinicians to match the right drug to the right person at the right time.
WILL THIS DRUG REPAIR DAMAGE TO THE BODY?
Researchers are testing a new drug that aims to repair damage to the myelin that is destroyed in MS. The cells that make myelin can initially repair it, but as MS progresses, there is little spontaneous repair. While current treatments aim to slow the progression of the disease, there are no approved therapies that stimulate the repair or regrowth of myelin once it has been damaged. Researchers are testing rHIgM22, a drug that in preclinical studies promoted remyelination and also showed sustained improvements in motor activity. Dr. Kita is currently enrolling participants in this study.
DOES MS THAT MOSTLY AFFECTS THE BRAIN DIFFER FROM THE ONE THAT MOSTLY AFFECTS THE SPINE?
Joan Goverman, PhD, at the University of Washington, noticed in a system model of MS that when the disease mostly affected the brain, it was immunologically different from when it mostly affected the spine. She is collaborating with Drs. Buckner and Kita on this inquiry to see if the same thing can be demonstrated in humans. With samples from the BRI biorepository of patients with MS, they are further studying immunological signatures of those who have MS mostly in the spinal cord versus those with disease confined primarily to the brain.
HOW DO PEOPLE WITH MS PROGRESS OVER TIME?
Dr. Buckner and her team are using the BRI biorepository to conduct studies of people with MS to understand their response to different medications and the differences when their disease is active or not active. She is looking for changes that can be recognized in blood samples that will signal a favorable response to treatment or a sign that disease might be more aggressive in a particular individual. Such signals would help to identify patients who are not responding to treatment or who might need more aggressive initial treatment. This historical snapshot can help scientists investigate individual disease progression over time.
January 1, 2016
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