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Archive for the 'Multiple Sclerosis' Category

Caffeine ‘could help prevent MS’

From BBC NEWS

Mice given the equivalent of six to eight cups of coffee a day were less likely to develop a disease similar to multiple sclerosis, a study found.

Researchers hope this could lead to new ways to prevent MS in humans.

The Proceedings of the National Academy of Sciences journal reported that the caffeine appeared to prevent nervous system damage.

However, experts recommend no more than five cups a day, amid evidence higher doses can worsen diabetes.

While the chain reaction which leads to multiple sclerosis is still not fully understood, a key moment surrounds the entry of immune cells into the central nervous system.

Once there, they trigger “autoimmune” attacks, gradually and progressively destroying the fatty myelin sheaths that protect nerves.

Current treatments for MS are limited only to slowing the progress of the disease once it is established.

At Cornell University in the US, and Turku University in Finland, the researchers are using a mouse disease called “experimental autoimmune encephalomyelitis”, or EAE, to mimic the development of MS in humans.

One of the effects of caffeine in both mice and humans affects a molecule called adenosine, which plays a role in sleep and energy production.

When mice were dosed with caffeine, adenosine could not link to a particular receptor on the surface of cells.

This in turn appeared to have an indirect effect on the ability of immune cells to enter the nervous system at a part of the brain called the choroid plexus, and the mice did not develop EAE.

While the precise reason this happened was not clear, the researchers suggested the adenosine blocking effect led to a lower number of “adhesion molecules” - needed by the immune cells to gain entry - on the surface of the choroid plexus.

Risks and benefits

Dr Linda Thompson, who led the study, said that the next step was to see if humans who drank plenty of coffee showed any signs of being less prone to MS.

“If you found a correlation between caffeine intake and reduced MS symptoms, that would point to further studies in humans.”

However, even if this were established, coffee might not be a good way to prevent MS.

The six to eight cups given to the mice is above the limit set by the Department of Health.

Other research has suggested that it might be physically addictive at these levels, and might worsen the control of type II diabetes, a far more common disease of older people.

A spokesman for the MS Society was also cautious: “Over the years there have been numerous discoveries that have prevented EAE in mice but turning this into effective therapies for humans remains a challenge.

“Based on the results of this study, we wouldn’t advise people to change their caffeine intake.”

 

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Multiple Sclerosis Drug May Be Linked to Melanoma

Doctors report 2 cases of the deadly skin cancer developing in patients taking Tysabri

From HealthDay

Almost immediately after a 46-year-old woman with multiple sclerosis received her first dose of the drug Tysabri, a mole that had been on her shoulder for years suddenly took on a dangerous new character.

It turned out to be a melanoma that spread like wildfire. The woman now has just a few months to live.

At almost the same time, a 45-year-old woman who also has multiple sclerosis developed melanoma in her retina after receiving several doses of Tysabri. She had a family history of melanoma and also had atypical moles on her body; the mole on her retina went back at least nine years.

Although these are just two — albeit dramatic — examples, the authors of a letter in the Feb. 7 issue of the New England Journal of Medicine are cautioning doctors who care for MS patients to keep this potential risk in mind.

“Neurologists who have patients who report a family history of melanoma or have funny moles should send them to a dermatologist first. Don’t just start them on drugs [Tysabri],” said Dr. John Thomas Mullen, co-author of the letter and a surgical oncologist with Beth Israel Deaconess Medical Center, in Boston.

“I can’t say it’s cause-and-effect definitively because it’s just an observation, but the first patient had had that mole forever. She took the drug and almost instantaneously the lesion changed,” added Mullen, who saw both patients.

“We don’t know if the two are related right now,” said Patricia O’Looney, vice president of biomedical research at the National Multiple Sclerosis Society. “There are so many people taking Tysabri, we should go forward with caution… One should always consult with their doctor and go over their personal family history and decide what is best.”

Tysabri (natalizumab), a monoclonal antibody that helps treat autoimmune disorders such as MS and Crohn’s disease, has had a clouded history. It first received U.S. Food and Drug Administration approval in November 2004, only to be pulled from the market three months later after several patients in clinical trials developed a rare but deadly viral infection of the brain called progressive multifocal leukoencephalopathy.

In June 2006, the FDA allowed the drug back on the market but with strict conditions governing its use.

Just last month, the FDA approved Tysabri to treat people with a moderate to severe form of Crohn’s disease.

But there is basic science to support Mullen’s observations.

One of the participants in an earlier study of Tysabri had developed (and subsequently died of) a metastatic melanoma that appeared as soon as he got his first dose of the drug, Mullen said.

And in a study done before Tysabri received FDA approval, melanomas in mice that were given the drug had an increased tendency to detach from the primary tumor and spread.

Tysabari may have a dampening effect on the immune system that encourages the formation of the potentially deadly skin cancer, the letter stated.

And now that Tysabri has been approved for people with Crohn’s disease, more people may be at risk, although those with no family history of melanoma and no moles probably don’t need to worry, Mullen said.

“Doctors should ask for a family history of melanoma and do a quick skin check,” he said. “Tysabri isn’t the only drug in our arsenal. You could give the patient something else if you were concerned about that.”

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Blood May Help Us Think

From ScienceDaily

MIT scientists propose that blood may help us think, in addition to its well-known role as the conveyor of fuel and oxygen to brain cells.

“We hypothesize that blood actively modulates how neurons process information,” explains Christopher Moore, a principle investigator in the McGovern Institute for Brain Research at MIT, in an invited review in the Journal of Neurophysiology. “Many lines of evidence suggest that blood does something more interesting than just delivering supplies. If it does modulate how neurons relay signals, that changes how we think the brain works.”

According to Moore’s Hemo-Neural Hypothesis, blood is not just a physiological support system but actually helps control brain activity. Specifically, localized changes in blood flow affect the activity of nearby neurons, changing how they transmit signals to each other and hence regulating information flow throughout the brain. Ongoing studies in Moore’s laboratory support this view, showing that blood flow does modulate individual neurons.

Moore’s theory has implications for understanding brain diseases such as Alzheimer’s, schizophrenia, multiple sclerosis and epilepsy. “Many neurological and psychiatric diseases have associated changes in the vasculature,” says Moore, who is also an assistant professor in MIT’s Department of Brain and Cognitive Sciences.

“Most people assume the symptoms of these diseases are a secondary consequence of damage to the neurons. But we propose that they may also be a causative factor in the disease process, and that insight suggests entirely new treatments.” For example, in epilepsy people often have abnormal blood vessels in the brain region where the seizures occur, and the hypothesis suggests this abnormal flow may induce epileptic onset. If so, drugs that affect blood flow may provide an alternative to current therapies.

The hypothesis also has important implications for functional magnetic resonance imaging, or fMRI, a widely used brain scanning method that indicates local changes in blood flow. “Scientists looking at fMRI currently regard blood flow and volume changes as a secondary process that only provides read-out of neural activity,” explains Rosa Cao, a graduate student in Moore’s lab and co-author of the paper. “If blood flow shapes neural activity and behavior, then fMRI is actually imaging a key contributor to information processing.”

Again, studies in Moore’s lab support this interpretation. For example, his fMRI studies of the sensory homunculus - the brain’s detailed map of body parts like fingers, toes, arms, and legs- show that when more blood flows to the area representing the fingertip, people more readily perceive a light tap on the finger. This suggests that blood affects the function of this brain region and that information about blood flow can predict future brain activity. This finding does not undermine prior studies, but adds another, richer layer to their interpretation and makes fMRI an even more useful tool than it already is.

How could blood flow affect brain activity? Blood contains diffusible factors that could leak out of vessels to affect neural activity, and changes to blood volume could affect the concentration of these factors. Also, neurons and support cells called glia may react to the mechanical forces of blood vessels expanding and contracting. In addition, blood influences the temperature of brain tissue, which affects neural activity.

To Moore’s knowledge, the Hemo-Neural Hypothesis offers an entirely new way of looking at the brain. “No one ever includes blood flow in models of information processing in the brain,” he asserts. One historical exception is the philosopher Aristotle, who thought the circulatory system was responsible for thoughts and emotions. Perhaps the ancient Greeks were on to something.

This work was funded by Thomas F. Peterson, the Mitsui Foundation and the McGovern Institute for Brain Research at MIT.

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Testosterone Treatment for Multiple Sclerosis

While many of the currently used pharmaceutical interventions in the treatment of multiple sclerosis (MS) are designed to reduce the risk of developing new brain lesions, precious little attention has been paid to exploring interventions that target two other consequences of this disease - impaired cognitive function and brain atrophy.

UCLA researchers recently published their work in the journal Archives of Neurology Arch Neurol in which they described treating men with MS with testosterone gel. Subjects received testosterone in the form of a topical gel providing 100mg of testosterone each day for 1 year. At the end of the study, the use of the testosterone gel was associated with an actual improvement in cognitive function and a dramatic slowing in the rate of brain atrophy.

Testosterone gel is widely available at compounding pharmacies around the country but should be used under the direction of a physician.

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Vitamin D - more than just bone density

From Dr. Perlmutter:

I have posted alot of information asof late dealing with boththe widespread nature of vitamin D deficiency in our society, as well as the various health implications of same. We used to believe that the main reason to pay attention to vitamin D status was in relation to bone mass. We now know that the health implications of this fat soluble vitamin are vast and include modulation of the immune system. Thisexplains why there is such an intense focus on vitamin D in cancer research as well as in autoimmune diseases like diabetes, lupus, and inflammatory boweldisorders. The prototypic autoimmune disease of the nervous system is multiple sclerosis. Hence, the citation below is timely and interesting.

Sunlight in Youth Might Shield Against MS

But experts warn that too much sun poses skin cancer riskFrom HealthDay

A new study of identical twins suggests that children who spend more time in the sun have a lower risk for developing multiple sclerosis (MS) as adults.

“Evidence is building up that something in relation to sunlight and/or vitamin D exposure during childhood may play a protective role,” said study co-author Dr. Thomas M. Mack, of the department of preventive medicine, Keck School of Medicine, University of Southern California, Los Angeles. “It’s now been suggested by several different studies that this is the case, and if it’s true, it would be important.”

The study is published in the July 24 issue of Neurology.

The findings echo those of a recent Harvard School of Public Health study, released in December and published in the Journal of the American Medical Association. That study found that among 140 white men and women, those with the highest levels of sunlight-derived vitamin D were 62 percent less likely to have developed MS than those with the lowest levels. The finding was not replicated in a smaller patient pool of either blacks or Hispanics, however.

According to the National Multiple Sclerosis Society (NMSS), MS is an autoimmune disease of the central nervous system that currently affects more than 400,000 Americans. More than 2.5 million men and women worldwide suffer from the disorder.

While it is unclear what causes MS, the often-crippling disease is thought to develop when the body’s own immune system begins attacking a fat and protein-laden substance called myelin that insulates nerve fibers.

Numbness, tingling, loss of coordination and balance, blindness, fatigue, and even paralysis can ensue, as normal communications between brain and body progressively collapse.

The majority of MS patients are first diagnosed between the ages of 20 and 50, and female patients outnumber males two-to-one.

In the study, Mack’s team assessed the sun exposure of 79 pairs of identical twins in the United States and Canada, in which at least one twin in each pair had been diagnosed with MS.

Most of the twins were girls, and among those with MS, most had been diagnosed between the ages of 20 and 40.

Each subject was asked about his or her childhood history of outdoor activity, as well as that of the twin.

Time spent tanning, going to the beach, and playing team sports during childhood was also noted. No absolute sun exposure measurements were recorded. Rather, the authors assessed relative degrees of sun exposure between twins, based on personal recall.

All participants were also asked to reveal any history of childhood infections as well as smoking habits.

The result: The twin with MS usually had been exposed to less sun overall as a child than the twin without the disease, the researchers found.

They observed, however, that this protective effect was only apparent among female twins. The lack of evidence among male twins could simply be a function of the relatively small number of male-male twins included in the study, the researchers said.

The degree to which the risk for developing MS was reduced as a result of increased sun exposure ranged from 25 percent to 57 percent, depending on what activity the disease-free twin had engaged in.

For example, the researchers determined that non-MS twins who had spent more childhood time sun-tanning than their sibling had a nearly 50 percent reduced risk of developing MS as an adult.

It’s not clear how sun exposure might protect against the illness. Ultraviolet rays might trigger a beneficial cellular immune response directly, or perhaps sunlight helps stave off the disease indirectly, by boosting vitamin D production.

To better understand the mystery behind sun exposure and its link to MS risk, the researchers said future sun-MS studies should be given “high priority.”

“If it’s true that sunlight is protective and/or vitamin D is protective, then there’s one group of people who ought to think seriously about it, and that is young parents who have MS,” noted Mack. “Because the likelihood that a child of a parent with MS will go on to get MS is 3 or 4 percent. Which is many, many times the likelihood that the average person could get MS.”

“So, I think if I was a young parent, and I or my wife had MS, and I had a child, I would want to take every step I could take to prevent my child from getting the disease,” added Mack. “But,” he cautioned, “the problem is, of course, that we know that too much sunlight is the cause of melanoma. So, that’s a dilemma. We want to give the child some exposure but not too much.”

Dr. John Richert, executive vice president for research and clinical programs at the NMSS, which co-sponsored the study, said that “we all have to take note of” the new findings.

“This is one of a series of reports over the last couple of years that have at least indirectly implicated the role of sun exposure and vitamin D production with susceptibility to MS,” he noted. “And this builds a stronger and stronger case that sun is one of the factors that can contribute to the development of MS.”

Richert observed that MS in general is more common the farther away from the equator one lives, particularly during childhood, further supporting the sunlight-MS link.

However, he also agreed that too much sunlight brings its own risks.

“Certainly, in terms of relative risk — skin cancer that can develop from sun exposure versus the potentially diminished risk for MS — we don’t have equations to really balance these,” Richert stressed. “And there’s a lot more work that still needs to be done before any kind of recommendations can be made about sun exposure or vitamin D intake.”

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