Progressive MS Alliance boosts research
by Mary E. King, PhD
Extract from Momentum magazine, published here with the permission of the National Multiple Sclerosis Society in the USA, a managing member of the Alliance.
Here’s a look at just three of the projects funded by the Alliance, which demonstrate the potential for these awards to quickly change the face of research in progressive MS. See the full list of all 22 projects.
Identifying biomarkers of progression
Two pressing questions for people with MS are “Will my disease progress in the near future?” and “Will my disease progress quickly or slowly?” Knowing the likely course of their disease can help them make important life decisions. And once new treatments become available, doctors would want to identify the people with rapidly advancing progressive disease who might benefit most from early aggressive treatment.
Dr. David Haegert, a professor in the department of pathology at McGill University in Montreal, and his team are looking closely at “biomarkers” that may forecast disease progression—in this case, proteins that are present on the surface of T cells, a type of immune cell found in the blood. Dr. Haegert’s team will look specifically for these biomarkers in blood samples from people with MS who participated in past clinical trials, and whose rate of disease progression is already known.
“We hope to identify a biomarker that is indeed increased in people with rapidly progressing MS but not in those whose MS is more benign,” explains Dr. Haegert. “If we can do this, then we want to develop a clinical test [using the biomarker] to predict disease progression.” He also hopes that a clinical test arising from this work using biomarkers on immune cells may help identify people with progressive MS who will respond well to treatments that target those immune cells.
Understanding progressive MS
Nerve cell damage is a hallmark of progressive MS, and one of the underlying reasons may be damage to nerve cell mitochondria, those tiny energy-producing factories found inside all cells. Mitochondria contain a small amount of special genetic material, called mitochondrial DNA (mtDNA), which program mitochondrial function and energy production.
Dr. Don Mahad, a Scottish Senior Clinical Fellow in the department for clinical neuroscience at the University of Edinburgh, explains, “The mtDNA found in nerve cells from people with progressive MS often contains mutations.” He and his team want to determine how easily these mutations develop in mitochondria from people with progressive MS. They will also investigate a potential relationship between the loss of myelin and changes to mitochondria.
Dr. Mahad continues, “The study may show a crucial role for damaged mitochondria in the progression of MS. If that is true, our results may identify ways to protect the nerve fibers and their mitochondria in people with progressive MS.” He points out that one possible limiting factor in this project is that the nerve cells used in the study will be derived from volunteers with MS, using skin biopsy, and because the cells are peripheral nerve cells, they “may not fully reflect the properties of those that are housed in the brain.”
Identifying effective rehabilitation programs
“Approximately 45 to 65 percent of people with MS develop memory deficits, primarily due to inefficient new learning,” says Nancy Chiaravalloti, PhD, director of neuropsychology and neuroscience and traumatic brain injury research at the Kessler Foundation Research Center in West Orange, New Jersey. “These changes are very disruptive to everyday life activities.”
Dr. Chiaravalloti and her team previously demonstrated that the modified “Story Memory Technique” (mSMT)—a practice that helps people to learn new information using imagery and context—improves learning and memory in people with MS. “The volunteers [in the earlier study] were mostly people with relapsing-remitting MS, however,” explains Dr. Chiaravalloti. The Alliance grant will allow her team to test whether mSMT will be helpful to people with progressive MS.
In the earlier research, participants received training in mSMT twice each week for 5 weeks, with each session lasting approximately one hour. After the training, participants demonstrated 10 percent or greater improvement in memory tests administered by the researchers. Just as importantly, the people with MS and their family members also reported significant improvement in the participants’ memory in everyday life activities. The trial included a control group that met with therapists but did not receive the same special training, and this group showed no improvement.
The investigators also saw increased brain activation in a subgroup of the study subjects when they were examined using a special type of brain imaging called “functional MRI,” additional evidence that mSMT changes brain activity.
The improvements in memory lasted for at least six months of follow-up, a very encouraging result. “The new study may help us address the troubling symptom of cognitive dysfunction and improve quality of life for people with progressive MS,” says Dr. Chiaravalloti.
Such research could not be undertaken without the support of the Progressive MS Alliance, she notes. “The Alliance is instrumental in providing resources to tackle critical problems in progressive MS, and, at the same time, developing new collaborations among top international scientists to develop additional research goals.”
Mary E. King, PhD, is a freelance medical writer in Boulder, Colorado.
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