June 27, 2014
Two Medical Meetings (ACTRIMS and CMSC) Focus on Research Progress and Issues in MS Clinical Care
“Basic and Clinical Research Issues” was the topic of the 15th
annual meeting of ACTRIMS (Americas Committee for Treatment and
Research in MS) on June 5
in San Antonio. This year, ACTRIMS was held in conjunction with
the annual meeting of the Consortium of MS Centers, as well as
the National MS Society’s
Tykeson Fellowship Conference. ACTRIMS was chaired by Jerry S.
Wolinsky, MD (The University of Texas Health Sciences Center at
Houston) and jointly sponsored by the National MS Society and the
University of Maryland School of Medicine, in collaboration with
the MS Society of Canada.
In all, 7 invited lectures and 68 platform and poster presentations were made at the ACTRIMS meeting; 20 cited funding from the National MS Society’s research programs. The complete program is posted to the ACTRIMS Web site at www.actrims.org. Here are some highlights of select invited lectures and platform presentations at ACTRIMS, followed by a summary of the CMSC conference:
Stem cell strategies:
The joint CMSC-ACTRIMS Donald Paty Memorial Lecture was delivered by Neil Scolding, MD (University of Bristol, UK), who discussed the pros and cons of stem cell therapy for MS. Dr. Scolding recently reported positive results from a Phase I safety/feasibility clinical trial of six people with long-standing MS, who were given intravenous injections of their own adult bone marrow cells containing a mix of stem cells.
Dr. Scolding commented that our increased understanding of MS has placed greater demands on potential cell therapies. We now know that therapeutic strategies need to address nerve fiber damage, which contributes to the development of disability, as well as areas of the brain that do not have obvious damage to nerve fiber-insulating myelin. However, findings in stem cell biology are keeping pace, giving hope that this strategy will bear out in an MS treatment. “We now know that bone marrow stem cells are able to leave the circulating blood stream and enter the brain and spinal cord, and that they do so in increased numbers when the nervous system is damaged or disease, as in MS,” he said.
Stefano Pluchino, MD, PhD (San Raffaele Scientific Institute, Milan) added to the discussion of stem cells, focusing on neural (nerve) stem cells. Dr. Pluchino’s team has shown that these cells can reverse the MS-like disease EAE in mice and stimulate repair of damaged tissues. Dr. Pluchino noted that stem cells probably do not work just by replacing other cells, but by orchestrating the activation of several mechanisms, including the release of immune-modulatory and tissue-supportive molecules.
Tanja Kuhlmann, MD (University Medical Hospital, Münster, Germany) talked about opportunities to stimulate “endogenous” repair – the repair capabilities that exist in people with MS, but that somehow fail to keep up with the damage. She noted several possibilities for why repair fails: inhibitors, such as the molecule Lingo-1; the lack of repair-promoting molecules, such as growth factors; or disturbed signaling pathways. Strategies for altering these obstructions are under study in MS models.
Managing treatment risks:
ACTRIMS also featured sessions on managing the apparent increase in treatment risk in more potent available and experimental MS treatments, such as the risk of developing PML (a brain infection that has occurred in people taking the MS drug natalizumab [Tysabri®, Biogen Idec and Elan]).
Russell Katz, MD, of the U.S. Food and Drug Administration, reviewed how that agency monitors risk during the process of drug development. Early on, toxicity in preclinical studies is evaluated to determine whether an agent is relevant for human subjects, and might preclude the possibility of human trials. When clinical trials are completed and the sponsor files for approval, the agency analyzes the trials information not only to evaluate effectiveness, but also to determine if the sponsor adequately defined and considered all aspects of the risks. Finally, post-marketing studies are often mandated to determine longer-term risks and how known risks can be managed.
Strategies that may help physicians and patients weigh risks and benefits of treatments were the focus of several presentations In a National MS Society-supported study of information materials related to natalizumab and risks of PML, Sascha Köpke, PhD, and colleagues at the University of Hamburg and other institutions across Germany found that after reading the materials, patients were generally more tolerant of safety risks than neurologists. The investigators point out the need for unbiased information to facilitate informed, shared decision making between patients and their treating physicians.
Treating mental health problems:
David Rintell, EdD (Brigham and Women’s Hospital, Boston) and colleagues reported on a massive effort to understand mental health problems in people with MS, funded by a Health Care Delivery and Policy contract from the National MS Society. Dr. Rintell’s team surveyed 3,300 people with MS and then queried 1,118 people who reported receiving mental health treatment about their experiences. Of these, 60% reported having mental health problems and 14% reported serious mental illness. Of those with serious mental illness, 44% received no mental health treatment. Of the 56% who did receive treatment, only half of these received it from mental health professionals; the others received mental health treatment from their primary care physician, neurologist, or a nurse. The results show the need to improve strategies for identifying and treating mental health problems in people with MS.
Oral teriflunomide results:
Mark Freedman, MD (University of Ottawa) and colleagues reported on phase II results of a study in which two different doses of an oral immune-modulating agent called teriflunomide (sanofi-aventis), or placebo, were added to ongoing interferon beta-1a therapy in 116 people with relapsing-remitting MS for one year. Disease activity as observed on MRI scans was reduced by 86% over placebo in the lower dose group, and by 82.8% over placebo in the higher dose group. The most frequently reported adverse events were upper respiratory tract infections, headaches, and gastrointestinal disorders. Liver enzyme elevation occurred, not exceeding three times the upper limit of normal. Larger-scale, phase III studies of teriflunomide are underway in relapsing MS and in people at high risk for MS.
Report from CMSC Annual Meeting
The Consortium of MS Center focuses on the clinical care of people with MS. A poster session held on June 4 featured both ACTRIMS and CMSC papers, facilitating networking among the many professionals – basic and clinical researchers, neurologists, and allied health professionals – attending these meetings. The full program, with abstracts, is available online (PDF). Here is just a small sample of more than 100 reports on research to improve the care of people with MS, focusing largely on platform presentations:
These occur in as many as one half of people with MS. Sharon Friedman-Urevich, RN (Winthrop University Hospital, Mineola, NY) administered paper-based questionnaires and a computerized cognitive test to 56 people with MS-related cognitive problems. Results of the computerized tests correlated significantly with the paper-based tests, indicating that this might be a cost-effective assessment program that could more easily identify decreases in cognitive function.
How to measure quality care:
Barbara G. Vickrey, MD, MPH (University of California, Los Angeles) was awarded a Health Care Delivery & Policy contract from the National MS Society to define what constitutes quality MS health care and how to measure it to establish better standards of care for people with MS. She led a team of MS specialists and social scientists to analyze the medical literature. The team then submitted their findings to a group of 15 stakeholders in MS care, including 4 people with MS, who rated each measure’s importance and impact. The most highly rated indicators were appropriateness and timeliness of the diagnostic work-up, bladder dysfunction, cognition dysfunction, depression, disease-modifying agent use, fatigue, and spasticity. In the future, these indicators will be further explored in studies to test new ways of delivering high-quality MS care, and to help clinicians and healthcare systems in evaluating the quality of the MS care they are providing.
What stops you from participating in community programs?
Karon Cook, PhD (University of Washington) and colleagues administered a questionnaire to 1271 people with MS, asking them to rate how 15 items affected their community participation: heat sensitivity, numbness, bowel or bladder problems, imbalance, problems thinking, sexual dysfunction, slurred speech, spasticity, swallowing problems, tremor, vision loss, arm weakness, leg weakness, fatigue, and pain. The strongest impediments were deemed to be weakness in the legs and fatigue. Research is needed to test whether interventions for these symptoms improve community participation.
This is one of the most common symptoms of MS, occurring in about 80% of people. Marcia Finlayson, MSc, OTR, PhD (University of Illinois at Chicago) and colleagues studied the effectiveness of a teleconference-delivered fatigue self-management program in 190 people with MS. The program comprised 6 weeks of 70-minute weekly sessions delivered by a licensed occupational therapist. Scores on a scale measuring fatigue and physical function improved significantly with the program and the improvements were maintained at 6-month follow-up; mental health showed significant improvement at 6-week follow-up. Telephone-based interventions can be an important addition to the fatigue treatment spectrum for people with MS who have mobility issues. This presentation won the meeting’s Patient and Family Education Award for Best Platform Presentation.
This symptom occurs in the majority of people with MS. Maria Lopes de Carvalho, MD, PhD, and colleagues (AISM Rehabilitation Centre, Italian Multiple Sclerosis Society, Genova) designed individualized, 12-session urinary rehabilitation programs for 62 people with MS (based on information derived from the individuals via questionnaires). Urinary incontinence decreased significantly, as did urinary retention. Further study may show such efforts to be another addition to treatment options for people with bladder dysfunction in MS. This presentation received the Research Award for Best Platform presentation at CMSC.
With information from the National MS Society (USA)
National Research and Programs