Research Advocate
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Studies on Oral Therapies Continue to Spark Excitement
The limitations of current therapies for multiple sclerosis have led to the development of several new oral drugs that target different parts of the MS disease process. The hope of ending injections continues to grow as the results of more studies on oral treatments are announced. Yet, effective oral treatments may not totally replace the need for the already proven injectable MS disease modifying agents.
In September of last year, the US FDA announced approval of fingolimod (Gilenya, Novartis), the first of the long-anticipated oral treatments for multiple sclerosis (MS). Fingolimod was found to reduce relapses and delay disability progression. It was approved for patients with relapsing forms of MS. Most recently, the results of Phase III clinical trials on two more oral treatments have been announced.
The initial results from the ALLEGRO study, an international Phase III trial on laquinimod (Teva Pharmaceuticals) were presented at the American Academy of Neurology meeting in April. Laquinimod is an oral drug which not only alters the immune system and protects myelin from attack, but it may also increase levels of some of the protective proteins and therefore provide even more benefits for MS such as prevention of neuroregeneration and brain atrophy. The data shows that laquinimod reduced annual relapse rate by 23%, the progression of disability by 36% and the progression of brain atrophy by 33% compared to placebo. It appears to be a drug that is safe and well tolerated, yet there is need for more long term data. The reduction in relapse rate was less effective for laquinimod than the relapse rate data for the currently approved injectable interferons and glatiramer acetate, but reduction in disability progression may be similar or even better. A current study will better determine if laquinimod is a more effective treatment than the current disease modifying agents. Disability progression for laquinimod was similar to Gilenya, but there are more safety concerns with Gilenya.
Biogen Idec announced in an April press release that the experimental oral therapy BG-12 significantly reduced the proportion of people with relapsing-remitting MS who had relapses in a 2-year study. It is reported to have a high safety profile as well. BG-12 strongly reduces inflammation and it strengthens the healing and protective cells and protein. Full details and evaluation of this study, and from another Phase 3 study now underway, should help define the safety and promise of BG-12 as a potential therapy for relapsing MS. In Europe (Germany) it has been used for many years to treat psoriasis, another autoimmune disease.
Very soon there will be many more treatment options for MS. People with MS and neurologists find the prospect of oral therapies for multiple sclerosis very appealing. They are more convenient and very powerful. While the excitement of ending injections forever is attractive to everyone, deciding on first line treatment choices must include balancing safety and effectiveness of the treatment choices. Choosing the right treatment for each person will involve weighing the risk , both long term and short, and benefit for each possible treatment. For patients already responding to their current MS treatments, there may be no need at all to add or switch to any new drug.
Resources to Find Clinical Trials
- ClinicalTrials.gov
- CenterWatch
- NARCOMS
- MS-CORE
- MS International Federation
- TCISCRP
- ResearchMatch.org
$17.5 Million for 50 New MS Research Projects
The National MS Society just launched 50 new MS research projects, with cumulative multiyear commitments of $17.5 million. These new projects are part of our comprehensive research program aimed at stopping MS, restoring function, and ending MS forever. The scope of this current launch is made possible by generous support of Society chapters and individual donors. When the National MS Society makes research commitments that span into future years, the money is not yet in hand to meet those needs. Contributions to the Society to help support these projects are essential to ensure that this important research proceeds in future years.
Following are brief summaries of the new research projects going on in our chapter’s states.
Rohit Bakshi, MD, Brigham and Women’s Hospital, Brookline, MA
Award: Research Grant, Term/Amount: 4/1/11-3/31/14; $389,511
“Magnetic resonance disease severity scale for MS” Developing a scale of novel imaging technologies to more accurately measure damage to the nervous system in MS.
In this research project, Rohit Bakshi, MD, is developing a composite scale that combines information from the latest MRI techniques to give a more complete evaluation of MS damage than has been possible in the past. This scale includes information about changes in the “gray matter” – the regions of the brain and spinal cord that contain nerve cells – to give a better clue about long-term disability. It also includes information about damage to the spinal cord, which has not been demonstrated adequately by more standard MRI techniques
This magnetic resonance disease severity scale should provide a more comprehensive indication of the clinical significance of MRI results, as well as provide a new way to measure the effectiveness of treatments in MS.
Julien Cohen-Adad, PhD, Massachusetts General Hospital, Charlestown, MA
Award: Postdoctoral fellowship, Term/Amount: 7/1/11-6/30/14; $156,515
“In vivo study of white and gray matter pathology in the spinal cord using 7T MRI.” Using high-powered imaging technology to reveal details of spinal cord damage in people with primary-progressive MS.
Julien Cohen-Adad, PhD, and colleagues are improving 7T MRI technology to get highly detailed images of the spinal cord. They are then using this new equipment to study the extent of damage to the gray matter of 20 people who have primary progressive MS (a type of MS with slowly worsening neurologic function), and correlating findings with clinical aspects of their disease.
The results of this study should shed light on how damage to the spinal cord contributes to MS symptoms and could provide new opportunities to evaluate therapies in clinical trials for MS.
Clare Baecher-Allan, PhD., Brigham and Women’s Hospital, Boston, MA
Award: Research Grant, Term/Amount: 4/1/11-3/31/14; $518,466
“Mechanisms of Treg resistance in patients with multiple sclerosis.” Looking for ways to restore the normal balance of the immune system to prevent it from attacking the nervous system in MS.
Clare Baecher-Allan, PhD, is studying the influence of an immune cell known as a regulatory T cell (Tregs). These cells ordinarily suppress the activity of other immune system cells that might damage the nervous system. Dr. Baecher-Allan and others have found that Tregs are somehow defective in people with MS, so their ability to control immune attacks is compromised. Now her team is examining immune cells isolated from people with MS to better understand how immune system cells escape from the control of Tregs and what genetic factors may be involved.
This research should help unravel why the normal regulation of the immune system fails in MS, and could lead to new treatments that restore regulation and shut off the attacks in MS.
Dimitry Krementsov, PhD, University of Vermont, Burlington, VT
Award: Postdoctoral fellowship, Term/Amount: 7/1/11-6/30/14; $150,800
Funded in part by the Greater New England Chapter in honor of Dr. Hill Panitch.
“p38 MAPK as a female-specific druggable target in autoimmune disease of the CNS.” Studying the effects of a drug that halts a disease similar to MS in female mice.
Dimitry Krementsov, PhD, is studying one of the immune system signaling pathways, “p38 MAPK,” which is activated in immune cells that attack myelin. His team has found that a drug that blocks the p38 MAPK pathway prevents or halts an MS-like disease in female mice, but has no effect on it in male mice. Now the team is working to determine how the drug works, why it is only effective in female mice and whether similar drugs may treat the disease in both sexes. This work could lead to new ways to prevent or stop disease activity in MS.
Scott Lovitch, MD, PhD, Brigham and Women’s Hospital, Boston, MA
Award: Postdoctoral fellowship, Term/Amount: 7/1/11-6/30/14; $162,481
“The role of PD-1 in maintenance of peripheral tolerance and control of EAE.” Studying how to manipulate a molecule to turn off immune system attacks in MS.
Scott Lovitch, MD, PhD, is studying the role of PD-1, a molecule that acts as a brake on immune system activity. Mice without PD -1 develop more severe EAE, an MS-like disease, while mice with increased levels of PD-1 are resistant to EAE. Dr. Lovitch is using mice in which the levels of PD-1 can be manipulated to determine how this molecule limits or prevents damage to myelin.
The results of this research could provide clues for developing MS therapeutic strategies that manipulate the function of PD-1.
Ralph Suarez, PhD, Harvard Medical School, Boston, MA
Funded by MS Hope for a Cure through the New York City-Southern New York Chapter
Term/Amount: 12/1/10-11/30/11; $44,000
“Functional magnetic resonance imaging of pediatric MS.” Measuring the ability of the brain to reorganize in early-stage MS to preserve cognitive function.
Carolyn Schwartz, DSc, Delta Quest Foundation, Concord, MA,
Funded by MS Hope for a Cure through the New York City-Southern New York Chapter
Term/Amount: 12/1/10-11/30/11; $44,000
“An investigation of cognitive reserve and appraisal processes in MS.” Characteristics of the mind that may contribute to the ability of an individual to preserve function in the face of damage caused by MS attacks.
Igor Koralnik, MD, Beth Israel Deaconess Medical Center, Boston, MA
Award: Research Grant, Term/Amount: 4/1/11-3/31/13; $182,567
“Mechanisms of JC virus reactivation and pathogenesis in multiple sclerosis.” Studying how to prevent a PML, potentially fatal brain infection, in people taking an approved MS therapy.
In this research grant, Igor Koralnik, MD, is studying JC virus in people with MS who have been treated with natalizumab versus those treated with other MS drugs and untreated controls. To determine how the virus becomes activated, Dr. Koralnik is measuring the levels of JC virus in blood and other bodily fluids, looking at how immune system cells react to JC virus, and how the virus is spread through the body. In addition, he is studying brain tissue derived via autopsy from someone who died of PML to see how the infection interacts with regions of myelin damage due to MS.
This research could lead to clues to how the JC virus might be blocked to prevent PML.
Nikolaos Patsopoulos, MD, PhD, Brigham and Women’s Hospital, Boston, MA
Award: Postdoctoral fellowship. Term/Amount: 7/1/11-6/30/13; $102,324
“The role of common, low-frequency and rare variation in the etiology of MS.” Identifying variations in genes that may be important in the risk of developing MS.
Nikolaos Patsopoulos, MD, PhD, is analyzing combined data from eight different studies looking for MS susceptibility genes. This “meta-analysis” will compare genetic information from more than 17,000 people with MS and 30,000 people who do not have the disease. Areas of the genome identified as contributing to MS will then be verified in a further group of 10,000 people with MS and 10,000 people who do not have it.
The amount of genetic data available for this project makes it likely to identify new variations in genes that make small but important contributions to MS susceptibility. In addition, this new information could lead to better understanding of the pathogenesis of MS.
For the latest research developments visit nationalMSsociety.org/Research and click on Research News.
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