World Congress on MS: Late-Breaking News and Rehabilitation Strategies
The final day of the World Congress on Treatment and Research in Multiple Sclerosis, held this week in Montreal, Quebec, featured progress understanding cognitive function and rehabilitation as well as late-breaking research on new therapies and new approaches to studying MS. The Plenary session's Leonor Gold Memorial Lecture by Nora Fernandez Liguori, MD, explored the history, promise and issues related to neurorehabilitation for treating cognitive dysfunction that results from MS.
Reports on Emerging and Current Therapies:
• Results of a second Phase 3 trial of sustained-release Fampridine (Acorda Therapeutics) showed that this symptomatic therapy could temporarily improve walking speed and leg strength in a subgroup of people with all types of MS. Andrew Goodman, MD (University of Rochester, New York) presented results of this trial of Fampridine-SR, a sustained-release formula of 4-aminopyridine that temporarily enhances nerve signaling. For nine weeks 120 people received fampridine versus 119 on placebo. The primary outcome measured was improvement in the time taken to walk 25 feet. About 43% of those on treatment showed consistent improvement in walking speed, versus about 9% of those on placebo. Among responders, speed improved by about 25% from baseline. The drug was well tolerated. According to the company, these results, combined with previous testing, will serve as the basis of an application for marketing approval. (Abstract P909)
• In the first attempt to apply a new “antisense” approach to treating MS, ATL1102 showed significant reduction in the accumulation of new active brain lesions over 8 weeks of treatment in a European Phase 2 trial. The study, presented by Volker Limmroth, MD, PhD (University of Cologne, Germany), was a placebo-controlled trial involving 77 people with relapsing-remitting MS who received twice weekly subcutaneous injections of the active agent or placebo. This proof-of-concept study requires followup with larger, longer clinical trials to verify this compound’s clinical effectiveness and safety. ATL1102 targets CD49d, a subunit of a T cell adhesion molecule that permits immune cells to migrate into the central nervous system. (Abstract 81)
• A short-term, controlled trial of a new formulation of Rebif® (interferon beta-1a, EMD Serono, Inc. and Pfizer, Inc.), delivered by subcutaneous injection, provided MRI evidence that the new formula has a rapid biological effect against new lesion development and was significantly beneficial on this measure than inactive placebo. The short-term study (16 weeks) involved 180 people with relapsing-remitting MS. This controlled study adds to previous findings from an open-label study suggesting the new formula is safe and well-tolerated. The new formula is approved for use in Europe and Canada, but has not yet been approved for use in the U.S. (Abstract P900)
• Disappointing results from a trial of the IV drug Rituxan® (rituximab, Genentech and Biogen Idec), which depletes immune B cells from circulation, may provide possible clues to future clinical trials in primary-progressive MS, a course of MS for which no treatments are currently on the market. Kathleen Hawker, MD (Ohio State University, Columbus, Oh.) presented results of a trial involving 439 people with primary-progressive MS, showing that the drug did not slow disease progression when compared with inactive placebo, the primary endpoint of the study.
However, secondary outcome measures using MRI showed the median change in lesion volume from baseline to week 96 was significantly lower in patients on therapy. Looking at subgroups of participants, the investigators found that those who were younger and showed MRI signs of active inflammatory lesions (gadolinium enhancement) appeared to benefit most from the therapy. This suggests some impact on underlying disease activity that should be factored into future trials of therapies for this progressive form of the disease. (Abstract 78)
• Low-dose naltrexone, a drug that blocks opioid receptors and is normally used to combat addiction, was the subject of several reports at the World Congress. Bruce Cree, MD (University of California San Francisco) presented results of an 8-week placebo-controlled, crossover clinical trial involving 80 individuals with different types of MS. Using a quality of life inventory (MSQLI), they found that those on the drug showed consistent improvement in mental health components of the survey, but not physical quality of life measures. (Abstract P899)
In earlier Congress reports, National MS Society-supported investigators at Pennsylvania State University (Hershey, Pa) reported that low-dose naltrexone could prevent, delay or reduce the severity of MS-like disease (EAE) in mice (Abstract P190), but that high-dose naltrexone was detrimental, exacerbating the disease in mice (Abstract P216).
MS and Cognitive Impairment
One theme of this morning’s sessions was cognitive dysfunction, a troubling symptom that often involves problems with memory, attention, and information processing speed, that can impact people with MS even early on in the disease course. Studies are underway in understanding the biological basis for these problems and in addressing them through cognitive rehabilitation.
• A study using an advanced magnetic resonance imaging technique (double inversion recovery) to evaluate the presence of lesions, or damaged areas, in the gray matter parts of the brain (cortex), and their possible association with congitive problems was described by Massimiliano Calabrese, MD (University of Padova, Italy). The team administered cognitive tests and also evaluated fatigue and depression in 70 people with MS, and compared the results to their images of intracortical lesions. They found that cognitive impairment, but not fatigue or depression, was associated with high volumes of intracortical lesions. (Abstract 75)
• In a related study, Flavia Nelson, MD (University of Texas Helath Science Center, Houston, Texas) and colleagues also showed a link between intracortical lesions and cognitive impairment. These types of lesions are not well detected using conventional MR imaging. More research is needed on the detection, treatment and prevention of cognitive impairment in MS. (Abstract P908)
Exploring Risk Factors
• MS has been linked to a variety of infectious triggers but to date none have been proven to cause the disease. Claude Genain, MD (California Pacific Medical Center, San Francisco) and colleagues are working on creating laboratory systems to investigate aspects of how an infectious agent could trigger the autoimmune attack on the brain and spinal cord in MS. Among the suspected infectious agents is Human Herpesvirus 6 (HHV6).
Reporting on a study funded in part by the National MS Society, he showed that marmosets are susceptible to HHV6 infection, and that the virus could induce central nervous system symptoms and direct myelin damage. Over time, two of the infected animals developed MS-like relapsing-remitting symtoms and delayed autoimmunity was detected against myelin proteins. This study shows a direct correlation between HHV-6 and neurological disease in marmosets. Dr. Genain speculated that such delayed, secondary autoimmune reactions observed in this study would probably hold true for other viruses that have affinity to the central nervous system. (Abstract 83)
The four days of the World Congress offered an impressive glimpse into the fast-moving progress being made by investigators around the world, in many different fields, toward better treatments and quality of life, prevention and a cure for multiple sclerosis.
Read summaries from previous days of the Congress: Day 1, Day 2, Day 3
To view the complete list of presentations and abstracts visit www.msmontreal.org and click on “Scientific Program” and then on “Itinerary Planner” Then follow the prompts.
Rebif is a registered trademark of EMD Serono, Inc.
Rituxan is a registered trademark of Genentech and Biogen Idec