Sex hormones, salsa dancing and new exploratory therapies moving through the pipeline were among the topics of over 600 presentations focusing on MS during the week of the American Academy of Neurology’s (AAN) annual meeting in Philadelphia in late April. More than 12,000 neurologists and other researchers convened to share progress in understanding and treating neurological diseases like MS.
Read blogs from the AAN meeting Explore scientific summaries (abstracts) on the AAN’s Website. Search specific words, authors or abstract numbers listed below.
Below are a few highlights from the many MS-related presentations focusing on stopping MS, restoring function, and ending MS forever. In most cases, studies presented are considered preliminary. Many of the results will be analyzed more thoroughly, and usually published in peer-reviewed medical journals. Confidence in a study’s findings grows when it is repeated by others, with similar results.
Stopping MS – Emerging Therapies
Many studies were presented showing continued benefit and safety of available therapies, and additional findings from novel therapies proceeding through the development pipeline.
New form of Avonex for relapsing MS: Results were presented from the second year of an international, phase 3 trial of peginterferon beta-1a in relapsing MS, a new form of Avonex® designed to stay in the body longer than the standard form. Previously reported results after the one-year placebo-controlled portion of the trial suggested that peginterferon injected under the skin every two or four weeks was effective in reducing relapse rates and also reduced the risk of progression of disability. For the second year, all participants received therapy including those previously on placebo, and results suggested that effectiveness and safety were maintained. Trial sponsor Biogen Idec has submitted peginterferon for regulatory approval. (Abstract S4.005)
Pregnancy hormone estriol: Dr. Rhonda Voskuhl (University of California, Los Angeles) presented preliminary results of a clinical trial of the pregnancy hormone estriol combined with Copaxone® in relapsing-remitting MS. This study was inspired by the observation that MS relapses are less frequent during later pregnancy, a time when estriol is at high levels. In this trial of 164 women, the investigators determined that oral estriol plus Copaxone reduced the rate of relapses after one-year by 47% compared to women taking Copaxone alone, and also showed significant positive benefits in the scores of cognition tests. These positive effects were not however maintained through the second year of the study – the reasons why are not clear, but a more thorough analysis might reveal some answers. Read more (Abstract S23.003)
Whipworm eggs: The “hygiene hypothesis” proposes that the increased frequency of autoimmune diseases like MS in industrialized countries is due to a reduction in exposures to infectious bacteria, viruses and parasites. This idea gave rise to a small clinical trial reported by Dr. John Fleming (University of Wisconsin) and colleagues, funded by the National MS Society. Participants drank a sports drink containing the eggs of a parasite called porcine whipworm (Helminth) every two weeks for ten months. The number of active brain lesions detected at the end of the trial by MRI was moderately reduced compared to the number of lesions detected at the beginning of the trial, and they also found evidence that the treatment could promote the activity of disease-suppressing white blood cells. This was a small trial and needs to be repeated in a larger number of participants before definite conclusions can be made. (Abstract P3.149)
Ofatumumab in relapsing MS: Dr. Amit Bar-Or (Montreal Neurological Institute) presented results of a phase II trial testing different doses of ofatumumab in MS, funded by GlaxoSmithKline. This agent targets a type of white blood cell called a B cell, and is already approved for the treatment of B cell cancers. Investigators reported up to a 65% reduction in the number of active brain lesions detected by MRI in treated groups compared to the placebo groups. The most common adverse events were injection-related reactions. Five serious adverse events were reported in those who had received the high-dose regimen. These results add to previous studies with related agents and suggest that targeting B cells in MS is a promising approach. (Abstract I7-1.007)
Research Prize to Dr. Barry Arnason: The John Dystel Prize for MS Research was awarded to Professor Barry Arnason of the University of Chicago for discoveries that helped lay the groundwork for the development of immune-directed therapies in MS. Read more
Promising approach: Several presentations focused on early-stage molecules with potential to treat MS. One is IRX4204, a small molecule that selectively inhibits the activity of a receptor, or docking site, for a Vitamin A-like molecule called retinoic acid. Two studies suggested that IRX4204 may inhibit immune responses and promote the repair of myelin, the nerve fiber casing that’s damaged by MS immune attacks. If these early-stage lab studies hold up in further research, this has the potential to both stop immune responses that lead to nervous system damage and also repair what has been lost. (Abstracts S16.005, S16.006)
Stopping MS – Understanding Progression
More and more discoveries are helping us understand MS progression, or worsening – which most people with MS experience no matter what form of MS they are originally diagnosed with. Understanding the factors that drive progression will provide new approaches to stopping and reversing it to restore what’s been lost.
Early lead for progressive MS: Dr. Lior Mayo (Brigham and Women’s Hospital) and team investigated the potential of a vaccine-like therapy that stimulates cells that can turn off specific MS immune activity which is the hallmark of progressive phases of MS. The “anti-CD3” vaccine was given by the nose to mice with a disease similar to secondary-progressive MS, reducing symptoms after the onset of progression. This early study, funded in part by the Society, suggests this approach has potential. (Abstract S14.004)
Progression in Hispanics: Dr. Lilyana Amezcua (University of Southern California) and colleagues compared the disease status of Hispanics with MS who were born in the U.S. or who immigrated before the age of 15 with those who had immigrated to the U.S. after age 15 to see whether age at immigration influenced the degree of their MS disability. U.S.-born Hispanics and those who immigrated before the age of 15 were younger at symptom onset and had less disability compared to those who immigrated after age 15. (Abstract S34.008)
Progression and menopause: Dr. Riley Bove, who is funded by an American Brain Foundation-National MS Society Clinician Scientist Award, gathered information on MS during menopause from 391 women enrolled in a large-scale, long-term study at Brigham and Women’s Hospital in Boston. The results show that progression (measured with the standard EDSS scale) changed at or around menopause toward a more rapid accumulation of disability. The team is following up on this finding; if hormonal shifts are responsible, it may present an opportunity for find a solution for women with MS going through menopause. (Abstract P4.163)
Quit smoking to slow progression: Previous studies suggest that smoking cigarettes can both increase the risk of getting MS and the risk of progression. Good news from a study by Dr. Cris Constantinescu (Nottingham University Hospital) and colleagues suggests that stopping can significantly reduce the chance of progression. For every year that passes after a person stops smoking, they reported that the risk for progression was reduced by as much as five percent. (Abstract P6.141)
Novel imaging for progressive MS: Dr. Laura Airas (University of Turku, Finland) and collaborators at Oxford explored the use of a novel PET (positron emission tomography) tracer or marker designed to detect activated brain cells (microglia) involved in nervous system damage during the secondary-progressive phase of MS. The team was able detect detailed microglia activity in MS lesions and in myelin-rich areas of the brain that had no apparent lesions. Ultimately this technique could help fill an important gap to study disease damage and response to treatment, which may not be apparent using standard MRI or clinical assessments. (Abstract S44.003)
Imaging the spinal cord: Sometimes individuals’ MRI brain scans don’t show much MS activity, and yet they know they are having active disease. It’s possible the culprit is spinal cord lesions, but the narrow spinal column is more difficult to scan and study, and it’s not routinely done during checkups. A group led by Dr. David Miller (Queen Square, London) reported finding more spinal cord damage in people with progressive MS versus relapsing MS. They’ve also developed a way of measuring the load of this damage, which might be an important way to detect progression and repair in future clinical trials. (Abstract S13.007)
Stopping MS – Exploring Disease Activity
MS, taste, and smell: Alterations in taste and smell may be common issues for people with MS, and may represent a way to track underlying disease activity. In a small study, Dr. Gabriele de Luca (Oxford University) found that 12 of 17 people with MS had alterations in detecting smells, and that this issue correlated with damage to nerve-insulating myelin in the olfactory nerve. Dr. Felix Schmidt (University of Berlin) found that both smell and taste dysfunction correlated with MS disability scores (EDSS). (Abstracts P6.173, P6.165)
Toxic cells: Dr. Robert Lisak and collaborators at Wayne State University and the Montreal Neurological Institute reported that immune B cells taken from the blood of people with relapsing MS, but not those from healthy controls, secreted something that killed nerve cells growing in lab dishes. Previous work by the same team had also found that MS B cells were toxic to myelin-making cells. The toxic factor is not an obvious immune product such as immunoglobulin or complement. If the factor can be identified, it could lead to important insights and more focused therapies targeting B cells in MS. (Abstract P4.342)
MRI lesions predict relapses: Using a large dataset gathered from people with relapsing MS who participated in three clinical trials, Dr. Nancy Richert and colleagues (Biogen Idec) managed to track the impact of MRI-detected brain lesions, or spots of disease activity, on later disease course. They found that those who had one or more new or enlarging lesion (T2) during the first year were twice as likely to experience a relapse during the second year compared to those who did not have these lesions. The results verify that MRI scans can detect early signs of future activity and help inform treatment decisions. (Abstract P3.190)
Restoring Function – Wellness and Rehabilitation Approaches
Entire sessions at the AAN focused on important topics like “Diet and Hormonal Influences in MS” and “Cognition Fatigue in MS,” highlighting a growing awareness of diverse paths toward finding solutions for everyone with MS.
Plant-based diet: Dr. Vijayshree Yadav (Oregon Health & Science University) and colleagues studied the one-year results of a low-fat, plant-based diet on measures of disease activity, mobility, fatigue, cholesterol, body weight, and compliance in 61 people with relapsing-remitting MS. Half of the participants received 10 days of diet and cooking training, while the control group was wait-listed. Results show no significant changes in MRI scans, EDSS, or mobility. Fatigue scores improved significantly. Participants showed good compliance, and were able to lose weight and reduce cholesterol levels. Although larger studies are needed, these results help to fine-tune our understanding of how managing diet may help people with MS. (Abstract P6.152)
Restrain an arm, rebuild the brain: Dr. Victor Mark (University of Alabama at Birmingham) reported on constraint-induced (CI) movement therapy, which involves immobilizing the arm that a person favors, and forcing the arm weakened by MS to do exercises and skilled movements to promote increasing the use of that arm in daily life. In a study supported by the National MS Society, 20 people with progressive MS were enrolled in either a CI program or a control group involving activities such as aquatherapy, massage and yoga. Use of the weaker arm improved, and brain tissue in the cortex (the outer layer of the brain) increased significantly in those in the CI program, but not in the control group. If the findings hold up with further study, it could produce dramatic results from a relatively simple technique. (Abstract S23.007)
Cognitive function in kids: Dr. Lauren Krupp (State University of NY, Stony Brook) and researchers from the Network of Pediatric MS Centers – the Network is funded by the National MS Society – examined cognitive changes over two years in 67 kids with MS. The most common problems were visual or motor integration, information processing speed, and attention. Most children did not get worse over the two years. Addressing cognitive problems in children with MS is crucial to improve the lives of this small but important population in the MS community. (Abstract S33.004) Read more about managing school-related issues in kids with MS.
Salsa, anyone? Rosalind Mandelbaum, Dr. Albert Lo and colleagues (Brown University/Providence VA Medical Center) enrolled eight people with MS in a four-week salsa dance program. Individuals participated in dance sessions twice a week. Dancing resulted in significant improvements in gait and balance both right after the program and after three months of follow up. The National MS Society is now funding Dr. Lo and colleagues to conduct a larger study that may lead to more widespread use of dance as therapy to improve function in MS. (Abstract P3.053)
Magnetic stimulation for depression: Repetitive Transcranial Magnet Stimulation (rTMS) was approved by the FDA as a treatment for major depression. A device that generates electromagnet pulses is placed on the scalp with the idea of stimulating specific brain activity. Dr. Sven Schippling’s team (University of Zurich and others) randomly assigned 18 people with MS to receive rTMS sessions over six weeks and 10 people with MS to receive sham treatments. Half who received rTMS in an area of the brain known as the motor cortex showed significant decreases in depression, and a non-significant decrease in fatigue during treatment that increased to a significant difference during follow-up. Nine participants who received rTMS in another brain area and those who received sham treatments did not improve. Larger studies are needed to determine the safety and effectiveness of this treatment for MS symptoms. (Abstract S33.007)
Avonex is a registered trademark of Biogen Idec
Copaxone is a registered trademark of Teva Pharmaceutical Industries