Research

 

Medications

 

There is ongoing research looking for more effective, convenient, and tolerable treatments for relapsing-remitting MS; creation of therapies for the progressive subtypes; neuroprotection strategies; and effective symptomatic treatments. During the 2000s and 2010s, there has been approval of several oral drugs that are expected to gain in popularity and frequency of use. Several more oral drugs are under investigation, one being laquinimod, which was announced in August 2012 and is in a third phase III trial after mixed results in the previous ones. Similarly, studies aimed to improve the efficacy and ease of use of already existing therapies are occurring. This includes the use of new preparations such as the PEGylated version of interferon-β-1a, which it is hoped may be given at less frequent doses with similar effects. Request for approval ofpeginterferon beta-1a is expected during 2013. Monoclonal antibodies have also raised high levels of interest. Alemtuzumab, daclizumab, and CD20 monoclonal antibodies such as rituximab, ocrelizumab and ofatumumab have all shown some benefit and are under study as potential treatments. Their use has also been accompanied by the appearance of potentially dangerous adverse effects, the most important of which being opportunistic infections. Related to these investigations is the development of a test for JC virus antibodies, which might help to determine who is at greater risk of developing progressive multifocal leukoencephalopathy when taking natalizumab. While monoclonal antibodies will probably have some role in the treatment of the disease in the future, it is believed that it will be small due to the risks associated with them. Another research strategy is to evaluate the combined effectiveness of two or more drugs. The main rationale for using a number of medications in MS is that the involved treatments target different mechanisms and, therefore, their use is not necessarily exclusive. Synergies, in which one drug improves the effect of another are also possible, but there can also be drawbacks such as the blocking of the action of the other or worsened side-effects. There have been several trials of combined therapy, yet none have shown positive enough results to be considered as a useful treatment for MS. Research on neuroprotection and regenerative treatments, such as stem cell therapy, while of high importance, are in the early stages. Likewise, there are not any effective treatments for the progressive variants of the disease. Many of the newest drugs as well as those under development are probably going to be evaluated as therapies for PPMS or SPMS.

 

While diagnostic criteria are not expected to change in the near future, work to develop biomarkers that help with diagnosis and prediction of disease progression is ongoing. New diagnostic methods that are being investigated include work with anti-myelin antibodies, and studies with serum and cerebrospinal fluid, but none of them has yielded reliably positive results.

 

At the current time, there are no laboratory investigations that can predict prognosis. Several promising approaches have been proposed including: interleukin-6, nitric oxide and nitric oxide synthase, osteopontin, and fetuin-A. Since disease progression is the result of degeneration of neurons, the roles of proteins showing loss of nerve tissue such as neurofilaments, tau, and N-acetylaspartate are under investigation. Other effects include looking for biomarkers that distinguish between those who will and will not respond to medications.

 

Improvement in neuroimaging techniques such as positron emission tomography (PET) or magnetic resonance imaging (MRI) carry a promise for better diagnosis and prognosis predictions, although the effect of such improvements in daily medical practice may take several decades. Regarding MRI, there are several techniques that have already shown some usefulness in research settings and could be introduced into clinical practice, such as double-inversion recovery sequences, magnetization transfer, diffusion tensor, and functional magnetic resonance imaging. These techniques are more specific for the disease than existing ones, but still lack some standardization of acquisition protocols and the creation of normative values. There are other techniques under development that include contrast agents capable of measuring levels of peripheral macrophages, inflammation, or neuronal dysfunction, and techniques that measure iron deposition that could serve to determine the role of this feature in MS, or that of cerebral perfusion. Similarly, new PET radiotracers might serve as markers of altered processes such as brain inflammation, cortical pathology, apoptosis, or remylienation. Antibiodies against the Kir4.1 potassium channel maybe related to MS.

 

Chronic cerebrospinal venous insufficiency

 

In 2008, vascular surgeon Paolo Zamboni suggested that MS involves narrowing of the veins draining the brain, which he referred to as chronic cerebrospinal venous insufficiency (CCSVI). He found CCSVI in all patients with MS in his study, performed a surgical procedure, later called in the media the "liberation procedure" to correct it, and claimed that 73% of participants improved. This theory received significant attention in the media and among those with MS, especially in Canada. Concerns have been raised with Zamboni's research as it was neither blinded nor controlled, and its assumptions about the underlying cause of the disease is not backed by known data. Also, further studies have either not found a similar relationship or found one that is much less strong one, raising serious objections to the hypothesis. The "liberation procedure" has been criticized for resulting in serious complications and deaths with unproven benefits. It is, thus, as of 2013 not recommended for the treatment of MS. Additional research investigating the CCSVI hypothesis are underway.