خبر MS drugs may inhibit new lesion formation in the cortex

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The disease-modifying drugs currently available for MS have well-established effects on relapse rate and white matter lesion development. Whether they also help to protect gray matter has been an open question, primarily due to the difficulties in imaging gray matter lesions. However, since gray matter pathology has been linked with disability and cognitive dysfunction, it is important to learn what effect standard therapies might have in these regions

A team of scientists in Italy has performed a study on this topic using an MRI technique called double-inversion recovery (DIR), which is capable of imaging lesions in the cortex (the gray matter layer that constitutes the outer edge of the brain). Their study included 165 people with MS randomized to one of three treatments (two forms of interferon-beta and glatiramer acetate). Also included were 50 people with MS who chose not to be treated (due to benign course, needle phobia, pregnancy plans, etc.). Subjects were imaged at baseline and at 12 and 24 months

At both timepoints, the treated subjects were less likely to have developed new cortical lesions than the untreated subjects . The number of new cortical lesions was also lower in the treated vs. untreated subjects. Comparing across the different drugs, the largest effects were seen in those subjects taking IFN-b 1a 44 mcg subcutaneous 3x/week, followed by glatiramer acetate, followed by IFN-b 1a 30 mcg intramuscular 1x/week. These differences across drugs were greater at 12 months, and still present but less pronounced at 24 months. The treated subjects also had lower rates of gray matter atrophy compared with untreated subjects (no differences across drugs). As expected, white matter lesion development and relapse rates were also lower in the treated vs. untreated subjects

This study suggests that the first-line disease-modifying drugs for MS may curb lesion-promoting inflammation in the cortex as well as in the white matter. It is encouraging to think that this critical area of the brain could receive some protection by available MS drugs. Hopefully this line of investigation will be continued, and expanded to include the emerging MS drugs as well

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2011, Jan 12

Effect of disease-modifying drugs on cortical lesions and atrophy in relapsing-remitting

multiple sclerosis

 

The Multiple Sclerosis Centre of the Veneto Region, Department of Neurology, University Hospital of Padova, Padova, Italy

 

 

 

Abstract

 

 

Objective: To measure the effects of disease-modifying drugs (DMDs) on the development of cortical lesions (CL) and cortical atrophy in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: RRMS patients (n = 165) were randomized to subcutaneous (sc) interferon (IFN) beta-1a (44 mcg three times weekly), intramuscular (im) IFN beta-1a (30 mcg weekly) or glatiramer acetate (GA; 20 mg daily). The reference population comprised 50 untreated patients. Clinical and MRI examinations were performed at baseline, 12 months and 24 months. Results: One hundred and forty-one treated patients completed the study. After 12 months, 37/50 (74%) of untreated patients developed ≥1 new CL (mean 1.6), compared with 30/47 (64%) of im IFN beta-1a-treated patients (mean 1.2, p = 0.021), 24/48 (50%) of GA-treated patients (mean 0.8, p = 0.001) and 12/46 (26%) of sc IFN beta-1a-treated patients (mean 0.4, p

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Genetics/imaging study finds genes that affect brain biochemistry in MS

 

The University of California San Francisco has a substantial MS research program, with particular strengths in genetics and imaging. Scientists from both of these disciplines recently collaborated on a project to learn more about the role of inherited gene variants in MS. In addition to influencing who gets MS and who doesn't, genes may also affect the course or severity of disease, but this aspect of MS has not yet been as extensively explored

This project focused on the

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. Glutamate plays an important role in nerve signal transmission in the central nervous system, but it can be harmful to cells if concentrations are too high. Normally oligodendrocytes help to regulate glutamate concentrations by taking in excess glutamate, but this process is impaired in MS, and past research has documented elevated levels of glutamate in MS brains

The imaging researchers scanned the brains of 382 MS subjects using spectroscopy, which measures the level of different molecules in tissue. The geneticists performed a genome-wide genetics screen on the same subjects. The team then analyzed the genetic results with respect to the glutamate levels determined by spectroscopy. They found several variants in genes associated with glutamate biology that were more common in subjects having the highest concentrations of glutamate. Further analysis showed similar genetic associations in subjects with higher brain atrophy (shrinkage) and lower concentrations of a molecule found in axons (N-acetylaspartate).

These results suggest that inherent genetic differences in nervous system biology among people with MS may influence concentrations of glutamate within the central nervous system, which may then affect survival or death of axons. It is encouraging to see scientists from different disciplines coming together in MS research, because looking at a question from more than one angle can lead to a much better understanding of the disease

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FDA issues warning about medications containing oxybutynin

 

 

 

Jul 15, 2011

Some of medications (Ditropan®, Ditropan XL®, Gelnique® gel, Oxytrol® transdermal patch) used to treat urinary problems in people with MS contain oxybutynin. The FDA has added a warning to the labeling of these medications stating that angioedema (a swelling similar to hives that occurs under the skin) of the face, lips, tongue and/or larynx has been reported with oxybutynin taken orally. In some cases, angioedema occurred after the first dose; in other cases it occurred with later doses. The swelling was severe enough in some individuals to interfere with breathing and required hospitalization and emergency treatment. Although this reaction appears to be relatively rare, given the many years that oxybutynin has been used safely and successfully by people with MS and others, any person taking a medication containing oxybutynin who experiences swelling of the tongue or throat or difficulty breathing should stop the medication and seek immediate medical attention. Individuals who have questions or concerns about this medication should discuss them with their physician

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: Vitamin D Reduces Risk of Multiple Sclerosis

 

 

Numerous studies of MS have shown a correlation between disease frequency and geographic location, with the general rule being that as a person gets further away from the equator, their MS risk rises. This has often been reduced to sun exposure, with one of the more obvious implications being that sunlight causes the body to create Vitamin D--25-hydroxyvitamin D-- and therefore Vitamin D just might have a protective affect against MS

A new study released yesterday provides compelling statistics behind that claim, saying in short that Vitamin D seems to reduce the risk of developing MS in Caucasians.. While the study does not make any claims about people who already have MS benefiting from Vitamin D supplementation

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14

October 2011

 

 

The prospect of doing human clinical trials with stem cells to treat diseases like multiple sclerosis may be growing closer, say scientists at the University at Buffalo and the University at Rochester, who have developed a more precise way to isolate stem cells that will make myelin.

Myelin is the crucial fatty material that coats neurons and allows them to signal effectively. The inability to make myelin properly is the cause of MS as well as rare, fatal, childhood diseases, such as Krabbe's disease.

 

The research, published online and in the October issue of Nature Biotechnology, overcomes an important barrier to the use of stem cells from the brain in treating demyelinating diseases.

 

Until now, it has been difficult to separate out the right progenitor cells the ones that will develop into cells that make myelin, explains Fraser Sim, PhD, first and co-corresponding author on the paper and assistant professor in the Department of Pharmacology and Toxicology in the UB School of Medicine and Biomedical Sciences; he did much of the work while he was a researcher at Rochester.

 

"Characterizing and isolating the exact cells to use in stem cell therapy is one key to ultimately having success," said Sim. "You need to have the right cells in hand before you can even think about getting to a clinical trial to treat people. This is a significant step."

 

Sim and Rochester graduate student Crystal McClain ran extensive analyses looking at gene activity in different types of stem cells, leading to the conclusion that stem cells carrying a protein known as CD140a on their surface seemed to be most likely to become oligodendrocytes the type of brain cell that makes myelin.

 

The UB and Rochester scientists then injected the cells into the brains of mice that were born without the ability to make myelin. Twelve weeks later, the cells had become oligodendrocytes and had coated more than 40 percent of the brain's neurons with myelin a four-fold improvement over the team's previous results published in Cell Stem Cell and Nature Medicine.

 

"These cells are our best candidates right now for someday helping patients with M.S., or children with fatal hereditary myelin disorders," said Steven Goldman, MD, PhD, co-author, the leader of the team and professor and chair of the Department of Neurology at the University of Rochester Medical Center. "These cells migrate more effectively throughout the brain, and they myelinate other cells more quickly and more efficiently than any other cells assessed thus far. Now we finally have a cell type that we think is safe and effective enough to propose for clinical trials."

 

An eventual treatment of a disease like M.S. might involve injecting stem cells to create myelin in the brains of patients.

 

"Another approach," says Sim, "might involve using certain medications to turn on these cells already present in the brains of patients and thereby create new myelin. The use of the new techniques described in this work will permit us to better understand how human cells behave in the brain and help us predict which medications may be successful in the treatment of myelin loss."

 

The new approach may also be applicable to Krabbe's Disease, Sim says, which also involves the breakdown of myelin. Sim, who came to UB in 2009, is actively collaborating on related work with researchers at the Hunter James Kelly Research Institute, a partnership between UB and the Hunter's Hope Foundation and located in UB's New York State Center of Excellence in Bioinformatics and Life Sciences.

 

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About Teriflunomide

 

 

(Gothenburg, Sweden)

— Results of a phase 3 trial of teriflunomide, an oral disease-modifying therapy, showed a significant reduction in annualized multiple sclerosis (MS) relapse rates with 2 doses of the drug of more than 30% vs placebo

Disability progression was also significantly reduced by 30% with the higher 14-mg dose, and both doses were well tolerated, with a similar number of patients reporting treatment-emergent adverse events, including serious adverse events, in the treatment and placebo arms

"Certainly it's safe and effective and is a potential new oral monotherapy for MS with relapses and, again, potentially a first-line treatment given its combination of efficacy and safety characteristics," Paul O'Connor, MD, director of the MS Clinic at St. Michael's Hospital, Toronto, Ontario, Canada, and principal investigator of the TEMSO study told delegates here

The results were presented at the 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The TEMSO trial was funded by Sanofi-aventis