Too big to fail: a call for neurologists to speak up against rising cost of disease modifying treatments (DMTs). There are currently 12 FDA approved DMTs for the treatment of MS. The first DMT was introduced in 1993 (IFNβ-1b, Betaseron). Usually, an increase in the number of drugs available, in this case DMTs, would mean that the cost of these drugs should go down. However, this study has found that the cost of DMTs has increased significantly, on average increasing in cost by 21-36% over the past 20 years. For example, glatiramer acetate (Copaxone), increased from an estimated annual cost of $8,292 in 1993 to $59,158 in 2013. Compared to another drug, TNF inhibitor, this rate of change is significantly higher and is faster than inflation for other prescription drugs. This study is important because it carefully records this unexplainable increase in cost of DMTs for MS. The findings suggest that this may be due to a lack of control of drug prices and a lack of generic (no brand) drugs to drive prices down in the market for MS drugs. Although it is not clear why these prices are increasing so much, it is clear that this price raise may make it difficult for some people to get the treatment they need.
Link to article: http://www.neurology.org/content/early/2015/04/24/WNL.0000000000001608.short?rss=1
Expression of GM-CSF in T cells suppressed by IFNβ therapy. T cells, a kind of immune cell, play an important role in MS. Understanding what makes these cells different between patients with MS and healthy people is important for understanding MS and finding key targets for therapy. The role of T cells that produce an inflammatory cytokine, or protein, called GM-CSF has been defined in mice with MS but little has been studied in humans. This study sought to determine if T cells that produce GM-CSF are increased in patients with MS. They found that the numbers of T cells that produce GM-CSF are increased in patients with MS as compared to healthy donors, and these cells can also be found in lesions (areas of myelin loss) in the CNS of patients. This means these cells may play an important role at the site of disease. They also found that untreated patients had less of these cells than those treated with IFNβ, a prominent DMT. The authors show that IFNβ directly reduces the production of this cytokine, indicating a potential mechanism for how this drug works. All of these points are important because they support a key role of GM-CSF in MS. Also, understanding how IFNβ treatment works will help us understand the causes of MS and other ways to treat it.
Link to article: http://www.jimmunol.org/content/early/2015/04/25/jimmunol.1403243.abstract
Pools of T cells are similar between the central nervous system (CNS), cerebrospinal fluid (CSF) and the blood in patients with MS. Myelin specific T cells react to myelin antigens from the central nervous system, or the brain and the spinal cord. An antigen is a substance that causes the body to form antibodies against it, and when T cells find an antigen they recognize they grow and produce cytokines. It is thought that T cells that react to myelin antigens drive MS disease and lead to destruction of the myelin that insulates neurons. It is important that we identify what makes these cells different from cells that are not antigen reactive, and to understand if there is a difference between these cells in the blood and the CNS. One method for finding and tracking these antigen-specific T cells is through T cell receptor (TCR) repertoire analysis. When an antigen-specific T cell becomes activated, it will grow (this is called clonal expansion) and there will be more of its TCR in a given pool of cells. The goal of this study was to determine if this TCR repertoire was different between lesions in the CNS, the CSF, and the blood of MS patients. The authors found that there were clones of CD8 T cells in the CSF, CNS, and blood. There was also an overlap between the CSF and CNS. This means that the CD8 T cells may play a role in the processes that cause MS. More importantly, it is possible that taking a sample of the CSF may show what is happening in MS lesions. They also found a specific kind of CD8 T cell with certain markers on the surface (CCR5, LFA-1) that should be studied in more detail since these may be involved in causing the disease.
Link to article: http://onlinelibrary.wiley.com/doi/10.1002/acn3.199/full
New factors predict risk of disability accumulation over time. A clinically isolated syndrome (CIS) is defined as an episode that suggests inflammatory demyelination in the brain or spinal cord. Many patients who have a CIS can develop MS. A key question is what factors can predict whether a patient with CIS will develop MS? Knowing this is very important since it would allow for early treatment with disease modifying therapies (DMTs), and early treatment has been shown to significantly impact disease progress. The goal of this paper was to find out what factors, including clinical and radiological, can predict development of MS and how the disease progresses. They found that the presence of oligoclonal bands (proteins called immunoglobulins) in the cerebrospinal fluid (CSF) and the number of lesions (areas of demyelination) on brain imaging with magnetic resonance imaging (MRI) could predict whether or not a CIS will become MS. This study is important because it highlights clinical information that might help determine if someone with CIS is likely to develop MS. However, the number of patients in this study, or the sample size, was small (1,058 patient's data was included). This makes it hard to know if this information represents people with MS as a whole and future study is needed to confirm their findings.
Link to article: http://brain.oxfordjournals.org/content/early/2015/04/21/brain.awv105