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Home > MSAA Publications > The Motivator > The Motivator: Summer 2009 > Cover Story - MS Research Update 2009
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MS Research Update 2009

A comprehensive overview of the six FDA-approved disease-modifying therapies used to slow MS activity, along with initial findings on many experimental treatments presently being studied for the treatment of MS.

Written by Dr. Diana M. Schneider
Reviewed by Dr. Jack Burks
Edited by Susan Wells Courtney

Based on the positive response to the "MS Research Updates" appearing in the Summer 2007 and 2008 issues of The Motivator, this article incorporates new information about the six approved disease-modifying therapies (DMTs), as well as experimental drugs currently being studied for the treatment of MS. Highlights and recent research results are provided for each drug. This is not a complete list and not all studies and their results are included. Initial study results should be considered preliminary, as additional studies and/or evaluations may be needed.

This information is based on a wide range of sources, including the extensive journal literature on MS and its management, a review of ongoing clinical trials, and papers presented at major national and international conferences. These include the American Academy of Neurology (AAN), the Consortium of Multiple Sclerosis Centers (CMSC), and the American and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS and ECTRIMS).

A brief overview of MS terms and clinical trials has been included on the next page. For additional information, the "Health and Wellness" column from the Summer 2007 issue of The Motivator gives an overview of MS terminology, evaluative procedures, clinical trials, and treatments. To request a copy, please call MSAA at (800) 532-7667 or view it online at

Please note that this article does not include medications for managing the symptoms of MS. Treatments for symptom management are the subject of an article in the Winter/Spring 2009 issue of The Motivator. To view, download, or print a copy, please go to

Editor's note: MSAA does not endorse or recommend any specific products or therapies. Readers are advised to consult their physician before making any changes to their medication, diet, exercise, or other regimen.

FDA-Approved Medications

Experimental Oral Medications

Experimental Monoclonal Antibody Medications

Other Therapies Being Studied

New Directions in MS Research

Early treatment with one of the approved disease-modifying therapies (DMTs) is now recommended for all individuals with the relapsing forms of MS. People taking the "ABCR" drugs - Avonex, Betaseron, Copaxone, and Rebif - have had less disability, a lower annual relapse rate, reductions in the number and size of active lesions in the brain as shown on MRI, and a higher employment rate than untreated individuals. Additionally, early treatment of a single event suggestive of MS can slow progression to clinically defined disease.

Therapies for the progressive forms of MS still lag behind these impressive results for treating relapsing forms of MS, but research is now focused on a number of potential strategies for managing these more difficult, progressive types of the disease, and a few Phase III studies are now ongoing for SPMS and PPMS.

Identifying factors that predict a positive long-term outcome, as indicated by no clinical disease progression with the continued use of specific therapies, could assist in treatment decisions early in the course of RRMS. Conversely, advances are being made in attempts to determine early in therapy which participants may not respond optimally to treatment. This may allow researchers to identify those individuals who should receive alternative or additional therapy.

New drugs are based on new mechanisms, such as selective depletion of specific subtypes of lymphocytes or prevention of cell migration into the CNS. Some seem to act at least in part via a neuroprotective effect. Four monoclonal antibodies (MABs) have now shown efficacy in Phase II or III clinical trials: natalizumab (Tysabri®), rituximab (Rituxan®), daclizumab (Zenapax®), and alemtuzemab (Campath-1). Five oral agents have shown significant positive results in Phase II and/or Phase III trials: FTY-720 (Fingolimod®), BG-12, ABR-215062 (Laquinimod ®), teriflunomide, and leustatin (Cladribine®).

Environmental Factors and Genetic Studies

Genetic differences appear to exist between individuals who respond to interferon-beta treatment and those who do not. Australian researchers have discovered two new locations of genes that are linked to genetic susceptibility for MS. They also indicate a link between genetic susceptibility to MS and other autoimmune diseases, including Type 1 diabetes, rheumatoid arthritis, and Grave's disease (a thyroid disorder), and also the potential involvement of vitamin D metabolism (see previous page).

A study from Ireland found that a slight variation in the DNA (single-nucleotide polymorphism) predicts how early a relapse may occur while on interferon-beta treatment. Potentially, this may help clinicians identify individuals who are less likely to respond to treatment.

Slight genetic variants also may explain why African-Americans tend to have a more aggressive disease progression than Caucasians and may be less responsive to interferon-beta treatment.

New Therapies under Investigation

The preceding overview of approved and experimental drugs is only a fraction of the many treatments currently being studied. Some of the following are among the most exciting potential therapies under investigation.

Neuroprotective agents: The term "neuroprotection" refers to strategies designed to prevent irreversible damage of a variety of cell types in the CNS, as well as to promoting regeneration after MS-related damage has occurred, with the goal of preventing the development of disability. A variety of neuroprotective strategies are in the early stages of testing. Some of the drugs thought to have neuroprotective activity appear to reduce damage by blocking sodium channels or the release of the neurotransmitter, glutamate. Some of these drugs may decrease the toxicity of free radicals in the brain. A number of research studies are ongoing on a wide variety of agents that may have neuroprotective effects.

Bone marrow-derived stem-cell transplantation: High-dose immunosuppressive therapy followed by transplantation of the patient's own bone-marrow-derived stem cells has been used to prevent transplant rejection for many years. This same type of stem cell has been used in most MS studies, not embryonic or other types of stem cells. The procedure is being tested in MS when very active disease continues while on DMT. Evidence to date suggests that the therapy may be more successful in early stages of the disease.

In a Phase I/II study of 21 individuals with RRMS whose disease had continued to progress despite treatment with interferon-beta, 17 showed improvement of at least one point on the EDSS scale. Five of the 21 relapsed but achieved remission after further immunosuppression. After 37 months, all patients were free from progression, and 16 were free of relapses. Significant improvement was also seen in symptoms such as balance, walking, and weakness, as well as self-reported quality of life.

A Phase 1 safety study is being initiated at the Cleveland Clinic. The treatment being studied involves first removing and storing bone marrow cells, which are returned after the patient is immunosuppressed. This study has approximately 24 participants with relapsing forms of MS (approximately equal numbers with RRMS and SPMS) and evidence of involvement of the visual system. Other studies are ongoing.

Sex hormones: Estriol is an estrogen-like hormone that may have both neuroprotective and anti-inflammatory properties. Its possible use in MS was suggested by the fact that women with MS tend to have fewer relapses during pregnancy, but are often subject to relapses during the postpartum period, when the high levels of female steroids (hormones) present during pregnancy return to normal levels. Seven medical centers in the United States are conducting a two-year trial, enrolling 130 women with RRMS to receive daily Copaxone injections along with a daily estriol pill or a placebo. Preliminary research suggests that estriol and similar steroids act by either preventing oligodendrocytes cell death and/or recruiting undeveloped oligodendrocytes for new myelin formation. Several studies are underway to attempt to uncover the mechanisms through which this effect may occur.

Parasites: There is some evidence that infections such as gut parasites normally help to regulate immune activity, and that the increase in autoimmune diseases in industrialized countries may in part be an unintended consequence of improved hygiene. Ongoing studies selectively expose individuals with autoimmune disease, including MS, to these organisms. Studies are investigating whether controlled infection with helminths (a group of worms that infect the gastrointestinal [GI] tract worldwide) will decrease the number of new gadolinium-enhancing lesions on MRI and increase the number of specific types of T cells; secondary measures will include the percentages of other types of T and B cells. (The parasites will be eradicated after 48 weeks.) A Phase I trial indicated that helminth ova are safe when used in individuals with RRMS.

Other Agents in Early Stages of Testing for Use in MS

Just prior to the printing of this article, the Phase II study of CDP323 was discontinued due to a lack of significant changes in MRI findings and possibly other clinical measures in the study population. CDP323 is an oral Tysabri-like drug that has a short half-life, meaning that it is removed from the body more rapidly than Tysabri. It was hoped that the drug would have less risk for PML than Tysabri. The cancelled study was evaluating the safety, tolerability, and MRI effects of CDP323 as compared to placebo.

A number of other agents have shown some encouraging immunomodulatory effects, either in animals or humans, and are being tested for possible future use in MS. These include: RTL1000 (recombinant T-cell receptor ligand), a highly selective protein that binds to and inactivates T cells; CGP77116, a small protein similar to myelin basic protein (MBP), designed to modify the immune reaction that destroys myelin; SB-683699, thought to reduce the number of active white blood cells entering the brain; RG2007, which may block a T-cell pathway involved in MS; CS-0777, an oral immunosuppressive drug in Phase I studies; flupirtin, a non-opioid analgesic drug that may have a neuroprotective effect; MK0812, which targets proteins known as chemokines that attract immune-system cells to areas of inflammation; and symadex, which inhibits a pathway involved in macrophage maturation.

Atacicept (ATX-MS-1467) is a "cocktail" of four peptides derived from human myelin basic protein. It appears to block the development of mature B cells and inhibits the survival of antibody-producing cells. The drug is now in Phase II trials to evaluate its safety and tolerability, and to determine whether it reduces CNS inflammation in RRMS on MRI. It is administered via subcutaneous injection.

Anti-Lingo-1 is a monoclonal antibody now being readied for its first human trial. Previous animal studies showed that it promotes spinal cord remyelination and axonal integrity in the animal model of MS (EAE).

A French study with masitinib, which targets mast cells, was tested in 35 patients with PPMS and SPMS. Over 18 months of treatment, EDSS scores remained stable in both treated and placebo groups with PPMS. In the SPMS group, the treated individuals remained stable, while the placebo group averaged an increase of one EDSS point.

MN-166 (ibudilast) is an orally administered small molecule with neuroprotective and anti-inflammatory properties. In the first year of a two-year study in individuals with RRMS, it significantly reduced the percentage of brain volume loss and prolonged time to first relapse by 157 days. It did not, however, significantly reduce cumulative new lesion count, which was the primary outcome measure of the study.

A Phase II study to evaluate the effectiveness of oral recombinant ovine interferon tau in RRMS indicated effectiveness over nine months in decreasing the number of new gadolinium-enhancing lesions. It also appeared to be both safe and well-tolerated.

A new clinical trial, now recruiting, will evaluate whether following a specific low-fat diet will improve brain damage as seen by MRI. It will also determine whether MS progression is decreased as indicated by clinical evaluation and symptoms.

A Japanese study of a synthetic vitamin A molecule seems to prevent early symptoms of MS by blocking the function of a specific type of T cell.

To Learn More about Clinical Trials

Anyone interested in additional information about the clinical trials discussed here, or anyone interested in participating in a clinical trial, may visit The National Multiple Sclerosis Society has a downloadable file containing information on clinical trials, which may be accessed at:

Closing Note

In summary, the future of disease-modifying therapies (DMTs) for MS looks bright, both in terms of new information on currently approved DMTs, as well as exciting results for emerging therapies. Because of their complex mechanisms of action and potential side effects, it will be important to weigh the benefits of new treatments against their possible risks.

Research continues into a wide variety of experimental therapies, including those that may be effective for individuals with the progressive types of MS, as well as those with relapsing disease who have not to date responded to any of the presently approved DMTs. Exciting new findings about the processes involved with the development of MS and the mechanisms by which it produces nervous system damage continue to be discovered. The coming years should bring many promising advancements in the treatment of all types of MS.

As always, your personal healthcare professionals will be your best guides to making the right decision for you. The great news is that effective treatments are available. The keys to success are to start therapy early in the disease when it is most effective in preventing the accumulation of nervous system damage, and to stay on therapy once you've begun.

Last Updated on Monday, 25 March 2013 11:44