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Since its creation in 1999, the Partners Multiple Sclerosis Center at Brigham and Women’s Hospital, led by Howard L. Weiner, MD, has been on the forefront of multiple sclerosis (MS) patient care and research. We have made major strides in our understanding and treatment of MS over the last 25 years. Over the last decade, we have made significant advances in our search for a cure for MS, including developing new drugs to ameliorate the disease, integrating MRI imaging to visualize the MS process, and understanding the immunologic basis of the disease. However, while we have made great progress, we still have much to learn about MS and how to treat it.

To design a program to cure MS, we must first define what a cure actually means. This is a question that patients with MS and their families often ask. On careful examination, there are actually three definitions of a cure. Our program is designed to make progress in each of these areas:

stopping theprogression of disease

reversing disabilityand loss of function

preventing theonset of MS

Because MS is a chronic disease, it requires a long-term research commitment to explore promising avenues that will lead to the next breakthrough in our understanding and treatment of it. To this end, the Partners Multiple Sclerosis Center has designated the period between 2005-2015 as a decade of discovery towards an MS cure. We have created an ambitious program that takes into account all aspects of the fight against MS. We hope to establish a new definition of the course of MS that will serve as a benchmark for the future and will have a major impact on the medical care of MS patients and MS clinical research.

We will determine the degree to which we are affecting the course of MS with current therapy and develop survival curves based on disability that can be geared to the individual patient. It is clear that MS is a heterogeneous disease, but subcategories are not well defined or understood. The identification of MS subgroups will benefit clinical care, the future of MS research, and the design of clinical trials. By linking MRI imaging, biomarkers and genetics to different sub-types of MS, we hope to develop a predictive model of MS.

 

We have identified five integrated projects to achieve our goal:

The natural history of MS in the era of treatment is unknown. There are no good longitudinal data on what happens to patients undergoing treatment with current MS drugs, how many benefit, to what degree and whether there are different sub-categories or responses to therapy. The ultimate measure of our ability to cure MS resides with clinical evaluation that demonstrates a patient is stable or improving. A key part to the program will involve detailed clinical follow-up of 3,000 patients over a ten-year period to create a longitudinal measure of the disease in individual patients as opposed to a single snapshot.

MRI has proven a major breakthrough in our understanding of MS allowing for the direct visualization of the disease process and inflammatory changes in the brain. However, we have reached a plateau in this area of research and the time has come to move to the next level of imaging, including 3-dimensional techniques and MRIs that segregate MS types and create predictive models of the disease.

With the deciphering of the human genome and the rapid advance in bioinformatics, including gene chip technology, the computerized analysis of multiple biologic variables is now possible. Biologic systems are very complex and require sophisticated informatics for interpretation. We will apply such complex informatics to our MS population, tracked through the Natural History Study that will include proteomics, gene expression, genetics, and immune phenotypes. This will require a large bio-informatics infrastructure to process and analyze this data and correlate it with clinical and MRI imaging

At the center of our project is the design, construction, and testing of an integrated computerized system that will synthesize clinical, genetic, MRI and immunologic data on a large cohort of MS patients to build a program that will define MRI phenotypes, predict patients who are likely to be responders or non-responders to therapy and assess the degree to which we are indeed curing MS.

We now know that MS has an inflammatory component and a degenerative component. We will initiate a drug discovery program that targets both of these areas to develop and test new types of anti-inflammatory drugs that are not given by injection and are designed to have stronger and better-understood mechanisms of action that can be monitored by blood testing. In addition, we will work on developing MS drugs to treat the degenerative phases of the disease and to rebuild myelin, currently a crucial unmet need in MS pharmacology. A program in this area will also incorporate stem cell research with the goal of moving these approaches from preclinical testing to clinical trials in MS patients.

As part of the Decade of Discovery, we will sponsor an annual symposium at which we will present our findings to the scientific community. We will also host a special educational session for our patients, their families and our donors.

In summary, we believe that this is an opportune time for the next major assault on MS. It is imperative that we apply the latest technology and advances in biology to bring our understanding and treatment of MS to the next level.

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