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The most significant progress on MS research in 2013
January 12, 2014

We now have a better idea of ​​what is causing the damage and the progression of MS, are considered more than ever, the benefits of early and ongoing treatment, and we know more about the factors that influence the mechanisms of brain repair body.

The progress of major research that occurred during 2013 , featuring new tracks and that are driving efforts to stop MS and end it forever, are what make this post, I hope you find it utility.

Here is a brief summary of the significant progress and research conducted during 2013 on multiple sclerosis, including links to the details below (further information on the exposed links below):


• The new oral therapy tecfifera was approved for relapsing MS by the FDA.

. Positive results of interferon beta-1a (Avonex) in relapsing MS led to an application to the FDA for marketing approval. Biogen Idec announced that a Phase III study of pegylated interferon beta-1a, which is injected under the skin either every two or four weeks reduced the relapse rate significantly more than placebo in a study of 1,500 people with relapsing MS reaching the primary endpoint. Peginterferon is a new formulation of the molecule of interferon beta-1a that lets you keep the effects in the body for longer periods of time. More data from this ongoing study, also called the ADVANCE study were presented at the annual meeting in March of the American Academy of Neurology. According to a press release, the company intends to submit for regulatory approval in the United States and the European Union in 2013.

Other studies related to t emerging erapias, were presented at the annual meeting of the American Academy of Neurology.:

Amiloride in progressive MS: This blood pressure medication by mouth has been tested in a small study of 14 people with primary progressive MS, as previously demonstrated (neuro) protective properties of nerves. Dr. Arun Tarunya Oxford University, with colleagues in the UK and the Netherlands, reported that after 3 years, treatment with amiloride resulted in reduced brain shrinkage associated with disease progression in compared to what was experienced before treatment. Further testing is beginning on a larger study in the United Kingdom, the National MS Society is helping to support through the MS Society in the UK.

Using Gilenya in progressive MS: A poster presentation by Dr. David Miller of University College London and an international team suggests that you are making good progress in a large trial of Gilenya ® which is supported by Novartis Pharmaceuticals Corporation . The study involved more than 1,000 participants with primary-progressive MS, and is designed to determine if Gilenya can slow MS disability compared with inactive placebo after 3-5 years of treatment. This is one of several large studies conducted this year on progressive MS.

New way of existing therapy for relapsing MS: Dr. Peter Calabresi, Johns Hopkins University, presented the results of international phase 3 trial of peginterferon beta-1a in relapsing MS, a new form of Avonex ® designed to remain in the body longer than the standard. Results of use for more than a year suggests that peginterferon is injected under the skin every two to four weeks, was effective in reducing relapse rates and also reduced the risk of progression of study continues discapacidad.Este for a second year.

Copaxone ® in less doses: Dr. Omar Khan, Wayne State University, Michigan, presented the results of a yearlong study phase 3 with support from Teva Pharmaceuticals, which suggests that the halving of the skin injections (twice the standard dose of Copaxone), performed three times a week, were effective in reducing relapses and disease activity controlled by MRI, which revealed no unexpected safety issues.

Switching Therapies: A large study in France called Enigm made ​​monitoring the impact of switching therapy Tysabri and Gilenya ® ® 200 people who switched treatment after an average 30 months to Tysabri, there was an interval of “washing” of 3 to 6 months. in which he was not given any treatment, during which I experienced a 32% recaída.Los researchers concluded that the change increases the possibility of reactivation of the disease, and that the washout period should not exceed 3 months.

More results on Tecfidera ™: An evaluation of two phase 3 trials of oral dimethyl fumarate (Tecfidera, Biogen Idec), recently approved by the FDA for relapsing MS, suggested that treatment begins to be effective against MS activity after 3 months used, and the effect was maintained during the two years of trials.

Extension studies: Several presentations focused on the results of the extension phase completed clinical trials in relapsing-remitting MS, including the following. These often include open periods where participants who were treated with placebo during the first trial were switched to active treatment and the other participants continue in therapy and evaluated for a period of time.
• Extension of a Phase 2 infusions Frequently ocrelizumab (Hoffmann-La Roche Ltd.) showed continued efficacy at week 144 in the majority who continued in the study and no new serious adverse events. Ocrelizumab still more trials of both, progressive relapsing and EM forms.
• A one year extension of a phase 3 study of oral laquinimod (Teva Pharmaceuticals) showed that the risk of disability progression was significantly reduced for those active treatment in the first instance against which the placebo was started and then switched to therapy during the extension phase began. Eel most common adverse event was elevated liver enzymes.
• A one year extension of two Phase 3 trials with alemtuzumab (Genzyme, a company Sanofi and Bayer HealthCare Pharmaceuticals) showed that there was a lasting benefit against relapse and progression without additional infusions of IV therapy. Adverse events were surguieron thyroid disorders and autoimmune disorders, and one person died from sepsis. Alemtuzumab is being evaluated by the FDA for marketing approval.
• A one year extension of a phase 2 trial of daclizumab high-yield process (DAC HYP, Biogen Idec and Abbott Biotherapeutics) showed that reductions in monthly injections skin continued to reduce relapses, MRI activity disease and progression of disease. There was one death due to autoimmune hepatitis and the incidence of serious infections, skin events and abnormalities in liver function tests were similar to those found in the original study.

Exploration of disease activity

Can trigger MS attacks with vaccines? ‘s Dr. Mauricio Farez of the Universidad del Salvador, Buenos Aires, Argentina reported on its analysis by considering whether the common vaccines are related to MS. Among its findings, reported that vaccination against yellow fever can significantly increase the risk of relapse in multiple sclerosis, suggesting that a person with MS who is planning a trip to a country where there is a greater risk of contracting yellow fever should discuss the risks and benefits of vaccination with a doctor.

Sugar and progression: do not know yet why MS progresses slowly in some people and others experience a rapid progression, but a small study by Drs. Wael Richeh, Jesus Lovera and colleagues at Louisiana State University sobering. They wondered if the blood sugar is related to levels of disability in MS, and found that people with higher glucose levels were more likely to have higher levels of disability. This important finding needs further study to demonstrate the role of blood sugar in MS progression.

Genes and children: Drs. Emmanuelle Waubant and Jennifer Graves of the University of California at San Francisco and colleagues describe the preliminary results of a study of 117 genes in children with MS, showing that a particular gene (rs4648356) was associated with a lower relapse rate, while another (rs11154801) was associated with a higher relapse rate. The study, which requires confirmation, was supported by the National MS Society and the Consortium of MS Centers.

Predictors / s Tools Disease onitoring
tool to track the progression: Dr. Nicholas LaRocca of the National MS Society described the efforts of the newly formed Consortium and Outcome Assessments EM to accelerate the development of more effective treatments for MS, particularly for progressive forms of multiple sclerosis. MSOAC is a coalition of industry, academia, patient representatives, government agencies and other regulations, and the National MS Society. Data from clinical trials and other studies completed MS and work with regulatory agencies will be analyzed to judge a new outcome measure a clinical report that can be used to track more sensitively and assess the impact of disease treatment and progression of disability in MS further testing in the future.

Predict who will respond to Copaxone ®: Drs. Francisco Quintana, Howard Weiner and team of Harvard and Brigham Women’s Hospital describe a study that analyzed serum samples from people with MS who were taking glatiramer acetate (Teva Pharmaceuticals). They were able to find the profiles of antibodies able to detect those who responded to therapy and those who did not. Further work to confirm these findings could lead to a method to know from the start if a person is benefiting from this treatment or not.

Restore: the area of research to study how to restore function focusing efforts to repair the nervous system and stimulate recovery of lost function through exercise, rehabilitation and other media are wide.

“Linking” the brain: Guest speaker Dr. Maria Assunta Rocca San Raffaele Hospital in Milan, Italy presented compelling data on how the brain reorganizes to accommodate the damage caused by multiple sclerosis. In one study, the team analyzed the impacts of a 12-week computer that focused on training to improve memory and attention assisted course. They had previously reported that it had improved attention and executive thinking skills. Using functional magnetic resonance imaging, which allows real-time view of the brain at work, found indications that the circuits and brain activity had increased in specific areas, which seemed to persist at least 6 months after completion of training.

Exercise and the brain: A small study of scientists supported by Drs Victoria Leavitt, John DeLuca and others, on the Kessler Foundation in New Jersey, tested the effects of aerobic exercise on the brain. Using MRI scans and memory tests, indications were found that aerobic exercise (30 minute sessions, 3 times a week, more than 3 months) improved memory and increased hippocampal volume, part of the brain involved in memory and other functions. These preliminary results require additional monitoring.

Exercise and fatigue: German researchers Drs. Stephan Schmidt of Bonn, Cologne and Marc Wonneberger studied the effects of long-term aerobic exercise to increase strength in people with MS. This study involved 60 people divided into two groups: those with fatigue and those without fatigue. Both groups had sessions of individualized resistance exercise on treadmills for 12 months. After 6 months of exercise, both groups had improved oxygen consumption, but beginning with fatigue, showed no improvement in their fatigue scores up to 9 months in the program.

Brain Power: Researchers from Milan and Kessler also studied that people with MS with more “brain reserve” (the larger brain size) and “cognitive reserve” (higher levels of cognitive leisure activities in their youth) had a lower risk for cognitive changes associated with MRI lesions. Even when brain size was accounted for, those with more cognitive reserve seem to have a lower risk of cognitive changes. Investigations are underway to determine whether enrichment activities can help build cognitive reserve.

Treatment of CCSVI in MS: First results of a controlled trial with endovascular treatment (percutaneous transluminal venous angioplasty) were submitted by Dres.Robert Zivadinov, Adnan Siddiqui and the team of the State University of New York at Buffalo. In this blinded study, 9 persons had angioplasty and 10 had a fake treatment. At six months, the team found no adverse effects of treatment, but also found that did not provide a sustained improvement in venous flow. They also found that those with increased outflow veins tend to have a higher activity of MS impairment demonstrated through the RM.

The prevalence of CCSVI in MS: Dr. Robert Fox, Claude Diaconu and a team from the Cleveland Clinic and Case Western Reserve studied the preliminary results of a study supported by the National MS Society CCSVI in 61 people with different types of MS and 20 people without MS. They used ultrasound techniques including technicians trained in CCSVI assessment were unaware of the health status of the participants. Although the change in the interpretation of the CCSVI criteria produced substantial differences in the proportion of participants who meet these criteria (20% to 40% of non-MS met criteria compared to 21.3% to 36.1% of the participating MS ), there was no significant difference between the non-MS and MS groups

. risk factors:

There were several reports focusing on risk factors that can contribute to make a person more likely to develop MS, including summaries supported by the National MS Society related studies with salt and immunological activity of MS and snuff :

Three studies published by collaborators at the University of Yale, Harvard and MIT / Broad Institute, suggest that dietary salt can accelerate the development of an MS-like disease in mice, and provide new insights into the activity of the immune system involved in MS. It has to be further investigated to confirm the role of salt in triggering MS, and to determine whether the reduction in salt can inhibit the immune attack in MS, these studies open new avenues for strategies that can reduce attacks EM.

The three documents listed in the prestigious scientific journal Nature: 1) Drs. David Hafler, Markus Kleinewietfeld, (Yale University and the Broad Institute of MIT and Harvard) and his colleagues studied the ability of salt to drive aggressive immune cells called Th17 cells in lab dishes and similar disease MS in mice, 2) Drs. Vijay Kuchroo, Aviv Regev, Chuan Wu (Harvard Medical School and the Broad Institute of MIT and Harvard) and others study on the molecular events that allow the salt to awaken and lead Th17 cells, and 3) Drs . Regev and Nir Yosef Kuchroo (Broad Institute of MIT and Harvard) and others study on the network of regulatory factors governing immune responses Th17 cells.

One study suggests that smoking increases a person believes interferon immunity , which could reduce the benefits of treatment. In a study of nearly 700 people whose medical records were reviewed by researchers in Sweden, smokers were significantly more likely to develop antibodies associated with immunity to beta interferon than nonsmokers. These neutralizing antibodies to interferon beta, may be associated with incomplete response to treatment.

Another line of research could lead to ways to prevent people from developing MS:

As in other diseases autoimmune s , multiple sclerosis is significantly more frequent (at least 2-3 times) in women than men. This gender difference has stimulated important research initiatives looking at the role of hormones in MS.
MS is not inherited, but genetics plays a role in who gets the disease. Although the risk of developing multiple sclerosis in the general population is 1/750, the risk increases to 1/40 in anyone who has a close relative (parent, sibling, child) with the disease. In families in which several people have been diagnosed with MS, the risk may be even greater. Although identical twins share the same genetic makeup, the risk of an identical twin 1/4-lo only means that some factor (s) other than genetics are involved.
While most people are diagnosed between the ages of 20 and 50 , MS can appear in l hildren and adolescents and older adults. The study of the disease in different age groups, could help scientists determine the cause of multiple sclerosis and explain why the course of the disease varies from person to person. Important questions such as why the disease appears early in some children and why people who are diagnosed after age 50 tend to have a more consistently progressive course, that primarily affects your ability to walk.
Everywhere in the world, MS is more common in northern latitudes that are farther from Ecuador and less common in areas closer to Ecuador. Researchers are now investigating whether increased exposure to sunlight and vitamin D may have a protective effect on people living near the Ecuador.
MS occurs in most ethnic groups, including African Americans, Asians and Hispanics / Latinos, but is most common in Caucasians with northern European ancestry . However, some ethnic groups such as the Inuit, Aboriginal and Maori, have few or no documented case of MS, regardless of where they live. These variations that occur even within geographic areas with the same climate suggest that geography, ethnicity and other factors interact in a complex manner.
Dystel Prize: The winner of this year’s John Dystel MS Research Award, given jointly by the National MS Society and the AAN, was Professor George Ebers, University of Oxford, UK. Presented his work on the influence of genes and environment in relation to multiple sclerosis develops.

Reproduction and risk of multiple sclerosis: Drs. Melinda Magyari, Per Solberg Sorensen and colleagues of the MS Center of Denmark in Copenhagen, analyzed the possible factors that may explain the increased incidence of MS in women for decades. Used as a database, the Danish MS Registry, which captures information about the most people in your country who has MS, found that pregnancy and childbirth offer significant protection against the development of MS , with a duration of up to 5 years. This and other studies may provide more clues about the influence of hormones and other factors in MS.

Environmental exposures: Drs. Ellen Mowry at Johns Hopkins, Lisa Barcellos at the University of California, Berkeley and his colleagues studied a proportion of women enrolled in the health care of Kaiser Permanente Northern California about their possible exposure to specific environmental factors. The results for some of the known risk factors, such as genes known to increase the risk of MS, vitamin D status, previous mononucleosis and smoking in order to find new possible factors were adjusted. Results, which require more study, show that women exposed to small animals and reptiles, may be protected from developing MS, while people permanently exposed to pet hair may have had a higher risk of MS.

• progressive MS : It starts therapy trial in primary-progressive MS and secondary progressive forms: Researchers at the Cleveland Clinic Foundation, are initiating a Phase II clinical trial of ibudilast (MN-166, MediciNova, Inc .), an agent oral anti-inflammatory , in 250 people with progressive forms of multiple sclerosis. The study is funded primarily by NeuroNEXT Network, an initiative of clinical trials at the National Institutes of Health, with additional support from MediciNova, the company that will supply ibudilast. The U.S. National MS Society, actively advocated this unique collaborative testing, and is also providing financial support, and that aligns with the strategic focus of the Company of progressive MS, and can answer important questions about the best ways to measure the benefits of therapies aimed at protecting the nervous system from MS system. The trial was conducted at 28 sites in the U.S. under the direction of the principal investigator Robert Fox, MD, MS, FAAN, Neurologist in the Mellen Center for Multiple Sclerosis at the Cleveland Clinic

The World Alliance of progressive MS held its first scientific meeting to identify challenges and opportunities, and released its first application for research applications to address gaps in knowledge and research tools.

Together, they had previously issued a report that identified five key research priorities . Teams of expert scientists met to explore these priority areas, and the Milan meeting, reported their findings and sought feedback from participants. Some highlights are:

Identifying Objectives and Opportunities restructuring for progressive MS
• To date, the large-scale genetic studies have identified more than 50 genes that influence susceptibility to MS, but so far have found no genetic differences between relapsing and progressive MS , nor was any identified gene to explain the severity of the disease. Additional studies, they can determine the extent to which genes and disease course for its sphere of influence and repair mechanisms that the body starts.
• As a part of the immune system is often activated, more in progressive versus relapsing MS, study the activity of brain cells called microglia, discovering new ways to drive safely this activity can be achieved a new production approach to developing new therapies.
• The development of treatments for progressive MS can be accelerated by tests approved therapies for other diseases involving nerve degeneration (reuse). However, there need to be investments and a clear path to allow off-patent drugs, can be used to study progressive MS.

Experimental models for preclinical evaluation of therapies
• Animal models of relapsing MS have been valuable for early testing of potential therapies. A deficiency of progressive disease models has hindered the development of therapies for progressive MS. Therefore there is an urgent need to modify the models that reproduce the clinical symptoms and underlying tissue damage seen in progressive MS.
few existing models allow the study of specific aspects of progression, such as damage and myelin repair.

• The progressive MS shows a single lesion is damage to the spinal cord and oxidative damage that accumulates with advancing age. More information about the disease progression and complications of aging, can lead to the development of new models for testing new drugs.

New clinical strategies:
• Testing new therapies in relapsing MS, getting through MRI a positive response by a phase II study in a very short period of time (six months). Currently there is no reading equivalent to 6 months, to monitor the successful development of progressive MS.
• There is a need for study of new “biomarkers” that measure the injury of the nerve fibers or integrity, and other factors that contribute to the disability progression. There is increasing evidence for the use of a candidate marker of nerve damage to the spinal fluid, called neurofilament , as well as an early reading for neuroprotection. There is a European consortium (Bio MS) for the investigation of cerebrospinal fluid biomarkers in MS, the researchers noted the continuing need for trials to include cerebrospinal fluid tests to make them more specific and informative.
• There are imaging biomarkers emerging that can detect the integrity of the brain and spinal cord, l which can be useful for both the phase II and phase III in progressive MS.
• new clinical trial designs that minimize the number of participants and duration of tests are needed to Most therapies can be tested more quickly at a lower cost.

Measures of clinical trial results and design
• There is a need for better ways to measure the success of therapy in progressive multiple sclerosis. The ideal measure would be sensitive to changes over time, and predictive of future changes.
• They are exploring new technologies such as smartphones and tablets, because of its potential to measure real-time impacts of treatments on daily activities and mobility.
• The need for a better classification of different types of progressive multiple sclerosis, to improve the chances of success of the favorable results of clinical trials.
• It will be important to take into account comorbidities (such as heart disease , obesity, etc.) and environmental factors / lifestyle factors of trial participants, which may influence individual responses to the outcomes of treatment and during the study.
• Improve data collection and study new software better data from previous clinical trials, patient registries and databases to help inform new trial designs and biomarkers.

Symptom Management and Rehabilitation
• Exercise seems a promising approach with potential benefits both physical and cognitive. Research is needed to determine how to keep people with supervised exercise beyond time-limited programs.
• more, larger well-controlled trials are needed to assess symptomatic therapies and methods of rehabilitation interventions cognitive rehabilitation in particular.
• There is an urgent need for programs for managing symptoms and exercise to improve the quality of life of those who are severely affected by MS progression.

• The researchers found a possible “biomarker “or indicator can help predict disease progression. Called Tob1 , a molecule associated with immune cells, and if confirmed will ultimately be used to identify people who are likely to develop MS after an initial attack.

• There is growing evidence in MS that mitochondria malfunction, that small part of the energy producers of the cells (such as batteries), which may contribute to nervous system damage in multiple sclerosis, opens the possibility of research to prevent that damage.

• A report by the International Pediatric MS Study Group, highlighting optimal trial designs for the study of disease-modifying therapies in children with MS to improve their care.

Restore what has been lost

This year witnessed the growing evidence that exercise and rehabilitation can restore the physical and mental functions and help people with MS to live fuller lives.

• Nervous system repair:
. The first Phase 2 was launched from ” anti-LINGO “therapy research to stimulate myelin repair in people with MS
Two mouse studies in the U.S. and Italy, mostraronel potential of stem cells derived from the skin to produce new myelin and reduced damage to the nervous system. A co-funded by the National MS Society team transplanted derived stem cells from human skin into the brains of mice with a disease that prevents them to grow new myelin, the insulating material that surrounds nerve fibers that were damaged in MS . Found that the transplanted cells developed new myelin cells quickly and efficiently. Your Wang, PhD, Steven A. Goldman, MD, PhD (University of Rochester Medical Center, Rochester, NY). These preliminary findings highlight a new strategy that seems to reduce some of the risks of cell replacement strategies, but more research is needed to establish the safety and potential efficacy of this approach before it can be tried in people with MS.
o Barancik first prize winner on innovative technology , to find drugs to improve the potential for myelin repair,. the clinical trial is starting and is based on a drug covered by this system.
Studies or three laboratories provide basic clues about the damage to the nervous system and the factors that control myelin repair isolate brain, which if confirmed finally, it could lead to promising new therapeutic approaches to stimulate myelin repair to restore function in people with MS.
, or supported researchers using methods of non-invasive imaging, called PET (positron emission tomography) to visualize the loss and repair of myelin in rats with time, which can be used to identify compounds with potential for the future treatment of MS.

• Another step towards improving MS symptoms was taken when Canbex Therapeutics, for l anzar a clinical trial of an investigational oral therapy to treat l os muscle spasms (spasticity) experienced by many people with MS.

-A small study suggests that e l aerobic underwriting year has the potential overall benefits for people with MS, including improving brain memory circuits and construction. Aerobic exercise resulted in an increase of 16.5% in hippocampal volume, an increase of 53.7% in the memory, and a significant increase in the activity of the hippocampus. There were no significant changes in the person doing anaerobic exercise. The National MS Society is funding several studies that explore these potential benefits of exercise, including a test of aerobic exercise as a strategy for the treatment of cognitive dysfunction.

-A clinical trial showed a strong evidence that a specific type of memory training improves learning in people with MS and benefits of other aspects of quality of life. Researchers at Kessler Foundation in New Jersey report the results of a clinical trial showing that a specific type of memory training improves learning in people with MS for at least 6 months after the training is over, and also benefits other aspects of quality of life.

Additional studies were presented in exercise and rehabilitation in MS at ECTRIMS conference.

• Investment in development programs of therapy, focusing on new therapies to protect the nervous system damage in MS and / or stimulate myelin repair. These include NRP2945 of CuroNZ, NDC-1308 Neural ENDECE, ERbeta agonists Karo Bio AB, and selective inhibitor compounds Karyopharm Therapeutics Inc. ‘s Nuclear Export (SINE).

Progress was made to identify some factors that can combine to increase a person’s chances of developing MS, as specific genes, infections and lifestyle factors. None of these factors is one cause of the disease, and it is clear that not all who have multiple sclerosis have been exposed to these factors, or that all people exposed to these factors will develop MS. These tracks provide information that can lead you to discover ways to prevent the disease:

• A global consortium identified 48 novel risk genes that best define the biological processes leading to MS and may ultimately lead to ways to prevent disease and improve the design of better treatments. In the largest study of its kind, a worldwide collaboration of scientists has identified 48 new genetic variants associated with MS, bringing the total number of genetic variants that may influence susceptibility to MS is 110 . The study involved nearly 30,000 people with MS and 50,000 controls without MS, and was funded by more than 40 agencies and foundations. About 200 researchers from the International MS Genetics Consortium, representing 13 countries, published in Nature Genetics.

• One study suggested that the incidence of MS is higher in the African American women s than previously thought, and the researchers identified genetic differences between northern Europeans who have MS (see link below).

In summary, this has been a year of significant progress in research, bringing us closer to solutions for someday, hopefully near we can say that multiple sclerosis: heals.

Thank you very much for following me and I hope you find it useful information.

Jesus Santiago.

Links for further information:














Oxidative damage:





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