Multiple Perspectives in Multiple Sclerosis - April 13th 2015

A new antibody promotes recovery in the spinal chord and eye of rats after injury and inflammation. A new antibody targeted against a molecule known to inhibit the growth of neurons leads to recovery in an animal model of eye damage and MS. This antibody targets repulsive guidance molecule A (RGMa), which is a protein known to prevent neural regeneration and is expressed in the lesions of patients with progressive MS. By inhibiting this molecule, or preventing its action at the molecular level, researchers believe they prevent it from stopping recovery through its strong prevention of neural growth. Treatment of injured animals with this antibody against RGMa was shown to lead to increased remyelination and protection, indicating that targeting RGMa may be a viable method for regeneration therapy in MS. Link to article

Quest for new markers of MS disease in spinal fluid. The current standard for tracking disease in the central nervous system (CNS) is through MRIs, however, the presence of lesions found in the CNS through MRIs are not always associated with inflammation and relapse. This makes it difficult to diagnose and track disease progression. Using a variety of tests to determine the kinds of immune cells and other molecules called proteins in the spinal fluid of patients with relapse remitting MS (RRMS), primary progressive MS (PPMS) and other neurological conditions, researchers have found newer biomarkers that may help to better diagnose and track disease in patients. The presence of one protein, called sCD27, was shown to be highly predictive of CNS inflammation, along with other standard methods such as detection of another protein called IgG. It was also found that the presence of IL-12p40 was shown to accurately categorize MS disease subtypes, highlighting its potential use in diagnosis. In summary, this model, or decision process based on many measured factors from the CNS, can help to characterize patients disease and aid in diagnosis, which is notoriously challenging. Future work should build upon this model, where many measured factors can help to better diagnose and track disease over time, specifically in the CNS where disease is most active. Link to article
 
BREMSO: a new score for predicting course of MS disease. The ability to accurately predict the course of a complicated disease like MS would be beneficial to both patients and doctors by helping to inform treatment. Currently, no such summary score to help in this process exists, and disease progression prediction depends primarily on several different clinical factors that have not been combined in a useful way. Using data derived from MSBase, a data base of MS patient data, researchers have proposed such a predictive score called Bayesian Risk Estimate for MS at Onset (BRMSO). In short, a score is generated from clinical factors and demographics collected at disease onset, where patients with higher scores progress and those with lower scores are more likely to not progress. Overall, the researchers suggest that this new score be used to assess clinical trial outcomes or as a method to assess treatment outcomes, and could be used to inform treatment. Future work could benefit from including MRI information in the score, since this is not included currently, potentially due to the lack of clear MRI data in existing MS databases. Link to article

A call for more and better disease modifying treatments (DMTs) for MS. Relapses are a significant aspect of multiple sclerosis, and characterization of how relapse rate correlates with DMTs and more broadly to patient experience essential to better understanding relapses and how to better help patients. In order to evaluate treatment through individual patients, the North American Research Committee on Multiple Sclerosis (NARCOMS), administered a survey to 1000 participants. It was found that the most commonly reported treatment was corticosteroids, and neither gender nor MS type were associated with received treatment or current DMT. An average of ~7 new symptoms were reported to be associated with new relapses, mostly from patients with progressive MS, and the most commonly reported symptom of relapse overall was fatigue. Beyond all of the statistics, its clear that many patients reported effects of a relapse on life activities, including working and going to school. About three months after a relapse, only about half of the patients that responded reported feeling better. The authors admit their study was limited by those patients that responded to their survey, however their conclusions are clear: there is a need for improved DMTs given that patients with MS continue to experience relapses and the negative impact these episodes have. Link to article
 
Certain factors promote growth of choroid plexus cells. A type of cell called epithelial cells make up the choroid plexus, or tissue that produces spinal fluid in the brain. These cells are thought to be important because they make up the blood-brain barrier that protects the brain and can promote repair of injured brains. These cells grow very slowly, and it would be beneficial to identify factors that promote their growth, which could aid in recovery of brain injury. The authors of this study identified certain factors, mainly growth factors like epidermal growth factor, which promote the growth and recovery of these cells in mice. Future work should extend these to human cells, as well as explore additional growth cues that can promote repair and how growth might lead to improved function in the context of disease like MS. Link to article

Multiple Perspectives in Multiple Sclerosis is written by Brittany A. Goods, a PhD candidate at the MIT Department of Biological Engineering, and edited by Deborah Backus, PT, PhD, Director of Multiple Sclerosis Research at the Shepherd Center in Atlanta, GA.