Applying A Holistic Approach to Solve a Complex Disease

Multiple sclerosis is a complex disease involving immune-system attacks on the central nervous system.
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Multiple sclerosis (MS) is a complex disease involving immune-system attacks on the central nervous system. Research into MS involves questions that dovetail many fields of science, including immunology, neuroscience, psychology and more.    Promoting and funding collaborative research is one piece of the puzzle, receiving a great deal of media attention of late.   However, it is even more important to apply a multi-faceted, rather than a singular approach, if we are going to speed solutions to complex biological problems that will result in stopping MS, reversing its damage and ending the disease completely.

Finding therapeutic targets, validating qualified biomarkers for disease activities, and most importantly initiating clinical trials with effective outcome measures are all pivotal issues that require the entire community of researchers. 

We believe that a holistic strategy of supporting individual researchers along with multinational academic and commercial research teams will lead us to new treatments and ultimately cures faster than selecting a singular funding model. This year the National Multiple Sclerosis Society will commit $40 million to MS research that includes discovery research to advance knowledge; translational research to move initial academic and small biotech research discoveries through “the valley of death;” and clinical trials to advance breakthrough treatments that can change the lives of people living with MS.  

Realizing that translational research was one of the most vulnerable links in speeding needed treatments to people with MS, the Society established Fast Forward in 2007 as a wholly owned subsidiary to spearhead research in this area.  Fast Forward is already supporting projects in six young biotech firms, two of which have leverage that funding to secure pharmaceutical company support for phase 1 clinical trials.  It has also entered into a $19 million collaborative research project with a major pharmaceutical company targeting neural repair and protection research, funding four drug development projects in its first year.

Understanding the need to leverage assets and knowledge in pursuit of a common goal is leading to whole new levels of collaboration among MS researchers.  The National MS Society funded a $15 million international collaboration of more than one hundred researchers in the area of nerve repair and protection. This initiative has led to a critical first clinical trial repurposing an old drug phenytoin as a possible neuroprotective agent.   Founded with the help of Society funding, the International Consortium of MS Genetics is now composed of top research facilities that were once rivals in the race to identify all common gene variants that make people susceptible to MS. These are just two examples of the highly collaborative approach that embodies biomedical research today.

Another example is the Society’s Collaborative MS Research Center Awards. These five-year grants provide flexible funding to bring together scientists and physicians from diverse fields fosters cross-fertilization of ideas and techniques to propel progress. The Society has 12 active Centers focused on questions such as what causes MS damage and how to stop it (Yale, UCLA), searching for new therapies to stop MS (Dartmouth, University of Alabama), and how can the nervous system be repaired (Mayo Clinic, New York University).

This is not to say that much more needs to be done in the realm of collaboration and building stronger, effective pathways from laboratory discoveries to new treatments for people with MS.  However, it is unrealistic to think that solutions to the complex problem of speeding therapies to people with MS rests with one particular organization or model.  All of the MS therapies we have today resulted from contributions of academic researchers, non-profit, governmental, and private efforts.  Progress comes faster through an approach where all of the necessary “players” are involved in the solution.
 
We’ve started bringing together what may formerly have been considered unlikely allies: researchers from academia and pharmaceutical/biotech companies, along with leadership from research-active MS societies from around the world.  For example, the Society convened such a group for a think tank in Boston in December 2010, focusing on the challenges associated with progressive MS, for which there are few therapeutic options. 

The discussion reinforced the timeliness of the Society’s new Strategic Response to MS which is focusing on progressive MS.   Advances in pathology and imaging are yielding new information about progressive MS. We now know that progressive MS features “diffuse” or “smoldering” inflammation, rather than the acute immune attacks that are seen in relapsing MS. This inflammation appears to be driven by cells called microglia, immune cells that reside in the brain. More work is needed to understand their role, but they are already being targeted by therapies in the MS pipeline, another example of multi-faceted collaboration at work.

Also, non-conventional brain imaging techniques are offering new windows to see the nervous system injury that occurs during the course of MS. These techniques, such as DTI (diffusion tensor imaging), may be helpful for detecting whether the nervous system is being repaired or protected by experimental therapies.

Think tank participants noted recent findings suggesting that a proportion of individuals with progressive MS who shows signs of active inflammation on MRI scans are likely to respond to the disease-modifying therapies currently available for treating relapsing forms of MS. This makes it clear that we need to re-evaluate the clinical definitions of progressive types of MS and identify biological underpinnings that can improve treatment today, and also help determine whom to enroll in clinical trials.

As a follow-up to this think tank, we are now holding talks with MS Societies internationally to lay the groundwork for a consortium on progressive MS research.  And in May 2011 the Society and the European Committee for Treatment and Research in Multiple Sclerosis are convening an international workshop aimed at developing more sensitive outcome measurements for MS progression.  We need new ways – the quickest, most efficient ways – to determine if therapies are stopping MS symptoms from getting progressively worse.

The Society is committed to pursuing all promising avenues; connecting people, resources and ideas; speeding development of treatments; and identifying and filling gaps – until we have found a way to stop MS in its tracks, restore lost function, and ending this disease forever by identifying its cause.

To learn more about grant and other funding opportunities for academic institutions or young biotech  companies that might be working on innovative research projects that could lead to new or better therapies for people with MS, please visit www.nationalMSsociety.org.

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