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Federal research program takes aim at MS: the innovative research projects that focus on MS seek to improve assessment of and develop novel treatments for veterans and civilians living with MS.

* National MS Society activists led efforts to increase medical research funded through the Department of Defense.

* Innovative projects include efforts to understand MS pain symptoms and studies of repair strategies in the lab and in people with MS.

Over the past five years, the National MS Society has led advocacy efforts to garner more federal funds for MS research through the Congressionally Directed Medical Research Programs (CDMRP). More than $17 million has been allocated to MS research through the CDMRP, which utilizes Department of Defense funds for high-risk, high-reward medical research. Here are a few examples.

A clearer picture of MS pain

While working on a pain study at Dartmouth Medical School a few years ago, imaging expert and Society grantee Heather Wishart, PhD, was particularly struck by the fact that people with MS often reported high levels of pain, even when they were on treatment for pain. Although more than half of people with MS experience uncomfortable burning, tingling, shooting or stabbing sensations, the origins of MS pain remain murky and treatment is often inadequate.

With funding from the CDMRP, Dr. Wishart and her team are developing and testing the first functional MRI (fMRI)-based pain "metric" tailored specifically for patients with MS, to better track and understand MS pain. Pain metrics use a pain intensity scale to assess an individual's subjective experience, and the responses are then correlated with fMRI scans, which provide pictures of changes in brain activity. fMRI scans have been used to better understand pain in other conditions, such as chronic lower back pain and migraines, but until now, no such research had been done with MS.

The team's first task was to establish an MS pain metric using the least possible amount of stimulation. "We wanted a procedure that would allow us to effectively measure pain processing in MS without it being uncomfortable for participants, which is important if fMRI pain imaging is to become part of the normal protocol along with MRI," Dr. Wishart said. Her team fine-tuned a procedure that involves applying small degrees of blunt pressure to the thumbnail--just enough to be registered as mildly painful. The simultaneous fMRI reveals which regions of the brain are being activated, and to what degree.

Having a verifiable way to measure an individual's experience with MS pain could improve communication between people and their physicians, provide clinicians with an objective way to track this symptom over time, and help researchers evaluate the effectiveness of therapies. fMRI can also reveal how the disease affects the structure of the brain and help explain how these changes cause the painful sensations that are such a common and debilitating symptom of the disease.

Unlocking the door to myelin repair

Some damaged brain and spinal cord tissue has the potential to restore itself, but in MS, repair is impeded. CDMRP awarded a collaborative grant to Nitin Karandikar, MBBS, MD, PhD, whose field is immunology, and Qing "Richard" Lu, PhD (University of Texas, Southwestern Medical Center at Dallas), who is a developmental biologist, to investigate the biological mechanics of repair and develop an effective therapy that will allow repair to go forward.

Previous research by both labs identified "GPR17," a molecule that prevents immature myelin-making cells called oligodendrocyte precursor cells (OPCs) from maturing. OPCs have the capacity to make myelin, the protective covering that insulates and nurtures nerve fibers and which is damaged by the body's immune system in MS. Inflammation increases GPR17, and higher levels are apparent in damaged MS tissue.

The next phase is to find an effective method of disabling GPR17, which may stimulate repair activity. Dr. Karandikar is confident that "Our approach, if successful, should lead to clinical translation more easily, since some agents are already available."

Awarding this grant to Dr. Karandikar and Dr. Lu is a good example of CDMRP's commitment to high-risk, high-reward research projects. Dr. Lu's lab is studying mice with myelin damage induced by a toxin, while Dr. Karandikar's lab is utilizing mice with EAE, an MS-like disease. These parallel experiments provide two windows for understanding different types of myelin damage, and the research teams share data immediately. Drs. Karandikar and Lu got to know each other after they each received a Harry Weaver Neuroscience Scholar Award from the Society.

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In addition to the search for a novel therapeutic agent, the researchers will study how GPR17 affects the efficacy of current FDA-approved therapies. Controlling inflammation is an important component in treating the disease, but repair is also crucial. "We may have to treat MS more like we treat cancer," Dr. Karandikar predicts, "using a multipronged approach to target specific aspects of the disease process."

Translating stem cells into nerve repair

Another CDMRP-funded project is a trial studying the potential of mesenchymal stem cells (which can be derived from bone marrow and other parts of the body) to fight inflammation and to stimulate repair in relapsing MS. Principle investigator Jeffrey A. Cohen, MD (Cleveland Clinic Mellen Center for MS), is working with researchers at Cleveland's University Hospitals Case Medical Center and the National Center for Stem Cell and Regenerative Medicine. Phase I is to recruit 24 participants to evaluate feasibility, safety and tolerability.

Mesenchymal stem cells have been used successfully to regenerate bone, cartilage and tendons. These cells are able to evolve into many kinds of cells, including neurons, and they inhibit T-cell formation. These protective and regenerative factors make mesenchymal stem cells a promising candidate for stopping MS activity and stimulating tissue regeneration.

These projects are a great example of how the efforts of National MS Society activists, who have successfully pushed for increased CDMRP funding, can help to stop MS in its tracks and restore function to people living with the disease.

Lorna Smedman is a freelance writer living in New York City.
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Title Annotation:Research Now
Author:Smedman, Lorna
Publication:Momentum
Geographic Code:1USA
Date:Mar 3, 2012
Words:965
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