US scientists are testing a radical new theory that multiple sclerosis (MS) is caused by blockages in the veins that drain the brain. The University of Buffalo team were intrigued by the work of Italian researcher Dr Paolo Zamboni who claims 90% of MS is caused by narrowed veins. He says the restricted drainage, visible on scans, injures the brain leading to MS. He has already widened the blockages in a handful of patients. The US team want to replicate his earlier work before treating patients. Experts welcomed the research saying it was important to confirm the basic science before evaluating any therapy. MS is a long-term inflammatory condition of the central nervous system which affects the transfer of messages from the nervous system to the rest of the body.
The Buffalo team, led by Dr Robert Zivadinov, plan to recruit 1,100 patients with MS and 600 other volunteers as controls who are either healthy or have neurological diseases other than MS. Using Doppler ultrasound, they will scan the patients to see if they can find any blockages within the veins of the neck and brain. If they can prove Dr Zamboni's theory of "chronic cerebrospinal venous insufficiency", they say it will change our understanding of MS. Rewriting science Margaret Paroski, who is chief medical officer at Kaleida Health, where the Buffalo researchers are based, said the work could overturn prevailing wisdom that the damage in MS is predominantly the result of abnormal immune responses. "When I was in medical school, we thought peptic ulcer disease was due to stress. We now know that 80% of cases are due to a bacterial infection.
"Dr Zivadinov's work may lead to a whole different way of thinking about MS." Dr Zamboni, of the University of Ferrara, believes the blockages are the cause rather than the consequence of MS and that they allow iron from the blood to leak into the brain tissue, where it causes damage. He has performed procedures similar to angioplasty to unblock the veins and get the blood flowing normally again. He claims this "liberation procedure" can alleviate many of the symptoms of MS and is due to publish his findings in the Journal of Vascular Surgery. In an interview with CTV News in Canada he said: "I found the evidence of narrowing - narrowing of the veins just in MS patients. "I'm fully convinced that this is very, very important for people." Early days Kevin Lipp, an MS patient from the US, has been symptom-free since being treated by Dr Zamboni. He said: "It's only been 10 months. If nothing happens in the next two to three years, we'll know it's working." The BBC has heard anecdotally of other surgeons in Europe testing out the same treatment. The MS Society said more research was needed to see if this was an avenue that should be explored further. "This is not something patients can expect as a treatment now. This is experimental work and is being tested. We need to know more about its safety and effectiveness." Helen Yates, of the MS Resource Centre, said: "There is no doubt that this area warrants a great deal more study. "This could represent a completely novel approach to MS research which, if proven to be relevant, could be a "sea change" in the understanding of the mechanisms involved in the condition." |
Friday, November 27, 2009
Multiple sclerosis 'blood blockage theory' tested
This is not something patients can expect as a treatment now. This is experimental work and is being tested 
Tuesday, August 11, 2009
McGill/JGH researchers successfully reverse multiple sclerosis in animals
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mark.shainblum@mcgill.ca
514-398-2189
McGill University
New immune-suppressing treatment forces the disease into remission in mice
This release is available in French.
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A new experimental treatment for multiple sclerosis (MS) completely reverses the devastating autoimmune disorder in mice, and might work exactly the same way in humans, say researchers at the Jewish General Hospital Lady Davis Institute for Medical Research and McGill University in Montreal.
MS is an autoimmune disease in which the body's own immune response attacks the central nervous system, almost as if the body had become allergic to itself, leading to progressive physical and cognitive disability.
The new treatment, appropriately named GIFT15, puts MS into remission by suppressing the immune response. This means it might also be effective against other autoimmune disorders like Crohn's disease, lupus and arthritis, the researchers said, and could theoretically also control immune responses in organ transplant patients. Moreover, unlike earlier immune-supppressing therapies which rely on chemical pharamaceuticals, this approach is a personalized form of cellular therapy which utilizes the body's own cells to suppress immunity in a much more targeted way.
GIFT15 was discovered by a team led by Dr. Jacques Galipeau of the JGH Lady Davis Institute and McGill's Faculty of Medicine. The results were published August 9 in the prestigious journal Nature Medicine.
GIFT15 is composed of two proteins, GSM-CSF and interleukin-15, fused together artificially in the lab. Under normal circumstances, the individual proteins usually act to stimulate the immune system, but in their fused form, the equation reverses itself.
"You know those mythical animals that have the head of an eagle and the body of a lion? They're called chimeras. In a lyrical sense, that's what we've created," said Galipeau, a world-renowned expert in cell regeneration affiliated with the Segal Cancer Centre at the Jewish General and McGill's Centre for Translational Research. "GIFT15 is a new protein hormone composed of two distinct proteins, and when they're stuck together they lead to a completely unexpected biological effect."
This effect, explained Galipeau, converts B-cells -- a common form of white blood cell normally involved in immune response -- into powerful immune-suppressive cells. Unlike their better-known cousins, T-cells, naturally-occurring immune-suppressing B-cells are almost unknown in nature and the notion of using them to control immunity is very new.
"GIFT15 can take your normal, run-of-the-mill B-cells and convert them -- in a Superman or Jekyll -Hyde sort of way -- into these super-powerful B-regulatory cells," Galipeau explained. "We can do that in a petri dish. We took normal B-cells from mice, and sprinkled GIFT15 on them, which led to this Jekyll and Hyde effect.
"And when we gave them back intravenously to mice ill with multiple sclerosis, the disease went away."
MS must be caught in its earliest stages, Galipeau cautioned, and clinical studies are needed to test the treatment's efficacy and safety in humans. No significant side-effects showed up in the mice, he said, and the treatment was fully effective with a single dose.
"It's easy to collect B-cells from a patient," he added. "It's just like donating blood. We purify them in the lab, treat them with GIFT15 in a petri dish, and give them back to the patient. That's what we did in mice, and that's what we believe we could do in people. It would be very easy to take the next step, it's just a question of finding the financial resources and partnerships to make this a reality."
PLEASE NOTE: DR. GALIPEAU IS AVAILABLE FOR MEDIA INTERVIEWS ONLY AS OF WED., AUGUST 12.
Sunday, July 26, 2009
Common allergy drug reduces obesity and diabetes in mice
Crack open the latest medical textbook to the chapter on type 2, or adult-onset, diabetes, and you'll be hard pressed to find the term "immunology" anywhere. This is because metabolic conditions and immunologic conditions are, with a few exceptions, distant cousins.
However, a group of papers appearing in Nature Medicine, two of which are from Harvard Medical School researchers, have linked type 2 diabetes with immunology in a way that might persuade leading researchers to start viewing them as siblings.
In the first study, researchers used two common over-the-counter allergy medications to reduce both obesity and type 2 diabetes in mice. The medications, called Zaditor and cromolyn, stabilize a population of inflammatory immune cells called mast cells. In the second study, researchers found that a kind of white blood cell called a regulatory T cell, once thought to manage only other white blood cells, also acts as a liaison between the metabolic and immune systems—in this case, controlling inflammation in fat tissue. Fat tissue from obese and insulin-resistant mice and people is marked by a dramatic absence of this cell type, in dramatic contrast to an already reported overabundance in fat tissue of inflammatory immune cells called macrophages.
"It seems that we're seeing the emergence of a new biomedical discipline: immunometabolism," says HMS professor of pathology Diane Mathis, senior author on one of the papers.
Both papers will appear online July 26 in Nature Medicine.
Molecular garbage
Type 1 and type 2 diabetes both involve abnormalities in the insulin-producing beta cells of the pancreas, but their root causes are completely different. Type 1 diabetes is an autoimmune disease in which the immune system attacks the pancreas, destroying its ability to produce insulin. In contrast, type 2 diabetes is a strictly metabolic condition in which cells grow increasingly deaf to insulin signals and thus lose their ability to metabolize glucose. In both cases, glucose mounts in the blood, at times to fatal levels.But it is becoming increasingly clear that we should also think of type 2 diabetes in the context of immune function, Harvard scientists assert.
Guo-Ping Shi, Biochemist from the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, began to suspect such a connection when, in a previous study, he found mast cells present in a variety of inflammatory vascular diseases.
Mast cells are immune cells that facilitate healing in wounded tissue, primarily by increasing blood flow to the site. However, in certain conditions mast cells build up to levels far beyond what the body needs. As a result these cells become unstable and eventually, like punctured trash bags, leak molecular "garbage" into the tissue. This can result in chronic inflammation that causes asthma and certain allergies.
As Shi and postdoctoral research fellow Jian Liu discovered, mast cells were far more abundant in fat tissue from obese and diabetic humans and mice than they were in normal weight fat tissue. This led to an obvious question: by regulating mast cells, could we then control the symptoms?
To find out, Shi and colleagues took a group of obese and diabetic mice and, for a period of two months, treated them with either ketotifen fumarate (also called Zaditor) or cromolyn, both over-the-counter allergy drugs.
"We knew from published research that both cromolyn and Zaditor help stabilize mast cells in people suffering from allergy or asthma," said Shi. "It's almost as if the drugs place an extra layer of plastic on the ripped trash bag. So it seemed like a logical place to begin."
The mice were divided into four groups. The first was the control group; the second group was simply switched to a healthy diet; the third was given cromolyn or ketotifen fumarate; and the fourth was both given the drug and switched to a healthy diet.
While symptoms of the second group improved moderately, the third group demonstrated dramatic improvements in both body weight and diabetes. The fourth group exhibited nearly 100 percent recovery in all areas.
To bolster these findings, Shi and colleagues then took a group of mice whose ability to produce mast cells was genetically impaired. Despite three months of a diet rich in sugar and fat, these mice neither became obese nor developed diabetes.
"The best thing about these drugs is that we know it's safe for people," says Shi. "The remaining question now is: Will this also work for people?"
Shi now intends to test both cromolyn and ketotifen fumarate on obese and diabetic non-human primates.
Beyond friendly fire
In findings independent of Shi, researchers at Harvard Medical School and Joslin Diabetes Center discovered that a class of immune system cells called regulatory T cells, or Tregs, were abundant in the abdominal fat tissue of normal-weight humans and mice, but were virtually absent in the same tissue from obese and diabetic humans and mice.
Their numbers were inversely correlated with the numbers of a class of inflammatory immune cells, macrophages, in a sense creating parallel universes of fat. While obese and diabetic fat tissue was full of inflammatory macrophages and nearly absent of Tregs, normal-weight fat tissue was the diametric opposite.
"For immunologists this is very important, because Tregs had always been thought to control other T cells and that's it," says Markus Feuerer, a postdoctoral researcher in the lab of HMS professors of pathology Diane Mathis and Christophe Benoist. "But this is an entirely new concept." Mathis and Benoist collaborated on the study with Steven Shoelson, HMS professor of medicine at the Joslin Diabetes Center.
"I come at this studying the effects of obesity and why it can spread systemically to cause chronic health problems," says Shoelson, an endocrinologist. "It's possible that the inflammation caused by macrophages results in insulin resistance. And it's more likely, from what we've just seen, that Tregs are keeping the macrophages in check in normal fat tissue, thus preventing inflammation."
For over a decade, Tregs have been known as guardians for the immune system, ensuring that when white blood cells attack a foreign pathogen they don't become overzealous and harm healthy host tissue in a kind of friendly fire. Malfunctioning Tregs, however, have recently been implicated in diseases as diverse as multiple sclerosis and certain cancers.
"Now we're seeing that Tregs may be needed to prevent metabolic abnormalities as well," says Mathis. She adds, half joking, "As an immunologist, I always thought that type 2 diabetes was a pretty boring condition. After these findings, I'm starting to change my mind."
More information: "Genetic deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice" Nature Medicine, July 26, 2009, early online publication
Source: Harvard Medical SchoolSource
Saturday, September 20, 2008
Lack of vitamin D linked to multiple sclerosis
Children later diagnosed with multiple sclerosis had far lower levels of vitamin D than other youngsters, Canadian researchers reported yesterday in studies showing more links between the "sunshine" vitamin and disease.
These were the first studies to show the effects in children, although others have shown that adults who live in northern latitudes, who get less sun exposure, may have a higher risk of MS.
They also support a growing body of studies linking low vitamin D levels with disease, including cancer, heart disease, diabetes and tuberculosis.
Vitamin D, produced by the body when skin is exposed to sunlight, and also found in fatty fish, is added to other foods in many countries. Evidence suggests it helps lower blood pressure and boost the immune system.
Several studies presented at a meeting on MS in Montreal showed that children had low levels of vitamin D when they began to show evidence of the disease.
"Three-quarters of our subjects were below optimal levels for vitamin D," said Heather Hanwell, a graduate student in nutritional sciences at the University of Toronto, who led one study.
Hanwell's team studied 125 kids who had evidence of MS symptoms such as numbness. Twenty of the children were diagnosed with MS within the next year, Hanwell said. Blood tests showed 68 per cent of those children had vitamin D insufficiency.
On average, the children with MS had much lower levels of the vitamin than children who did not experience any other MS-like symptoms.
A study led by Brenda Banwell of Toronto's Hospital for Sick Children showed similar results.
"Seventeen of 19 children who had been diagnosed with MS had vitamin D levels below the target level," Banwell said.
The next step is to see if giving vitamin D supplements prevents MS or helps relieve symptoms, Banwell said. She said it was not clear how lacking vitamin D might be linked with MS.
Tuesday, August 12, 2008
Further evidence to link EBV virus infection with MS
Mon 30 Jun 2008
New research published in The Journal of Experimental Medicine has provided more evidence that a common human virus called Epstein Barr Virus (EBV) plays an important role in the development of MS.
In MS, lesions (or plaques) are patches in the central nervous system where inflammation has resulted in the loss of myelin, the protective sheath which surrounds nerve fibres. This study on 22 people with MS demonstrated that EBV is present in the lesions that attack myelin in almost all of the cases examined (21 out of 22).
The researchers propose that EBV is carried across the blood-brain barrier by a certain type of immune cell called B cells, the cells of the immune system that make antibodies. EBV infected B cells which accumulated in lesions were shown to be a common feature of MS, and the number of EBV infected cells correlated with the degree of brain inflammation.
The absence of EBV infected B cells in other inflammatory neurological conditions indicates that this may be specific to MS and not a general phenomenon driven by inflammation.
It is worth noting that EBV is one of the most common viruses in the environment, with up to 90 per cent of the population thought to have been infected by it at some time, most of whom do not go on to develop MS.
There is not yet enough data to prove that EBV infection causes MS. There needs to be further research to explain the link between EBV infection and MS.
Source 1
Source 2 (for date)
ARTICLE
Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain
1 Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità , 00161 Rome, Italy
2 Laboratory of Neuroimmunology, IRCCS Neurological Institute C. Mondino University of Pavia, 27100 Pavia, Italy
3 Department of Cellular & Molecular Neuroscience, Imperial College Faculty of Medicine, Charing Cross Hospital Campus, London W6 8RF, UK
4 Division of Infectious Diseases, San Raffaele Scientific Institute, 20127 Milano, Italy
5 Institute Pasteur-Cenci Bolognetti Foundation, Department of Experimental Medicine, University of Rome La Sapienza, 00161 Rome, Italy
6 Department of Neurology and Centro Neurologico Terapia Sperimentale (CENTERS), Ospedale S. Andrea, University of Rome La Sapienza, 00189 Rome, Italy
CORRESPONDENCE Francesca Aloisi: fos4@iss.it
Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, has been associated with multiple sclerosis (MS), an inflammatory disease of the central nervous system (CNS), but direct proof of its involvement in the disease is still missing. To test the idea that MS might result from perturbed EBV infection in the CNS, we investigated expression of EBV markers in postmortem brain tissue from MS cases with different clinical courses. Contrary to previous studies, we found evidence of EBV infection in a substantial proportion of brain-infiltrating B cells and plasma cells in nearly 100% of the MS cases examined (21 of 22), but not in other inflammatory neurological diseases. Ectopic B cell follicles forming in the cerebral meninges of some cases with secondary progressive MS were identified as major sites of EBV persistence. Expression of viral latent proteins was regularly observed in MS brains, whereas viral reactivation appeared restricted to ectopic B cell follicles and acute lesions. Activation of CD8+ T cells with signs of cytotoxicity toward plasma cells was also noted at sites of major accumulations of EBV-infected cells. Whether homing of EBV-infected B cells to the CNS is a primary event in MS development or the consequence of a still unknown disease-related process, we interpret these findings as evidence that EBV persistence and reactivation in the CNS play an important role in MS immunopathology.
Abbreviations used: AID, activation-induced cytidine deaminase; CNS, central nervous system; CSF, cerebrospinal fluid; EBER, EBV-encoded small nuclear mRNA; EBNA, Epstein-Barr nuclear antigen; HHV-6, human herpesvirus 6; LMP, latency membrane protein; MOG, myelin oligodendrocyte glycoprotein; MS, multiple sclerosis; OCB, oligoclonal IgG band; RA, rheumatoid arthritis.
Source
Full Text
Perhaps a note to
Francesca Aloisi: fos4@iss.it
Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità , 00161 Rome, Italy
is indicated noting Nanoviricides' interest and capabilities suggesting a cooperative approach to remove EBV from the MS picture.
Wednesday, July 16, 2008
Vitamin D and Multiple Sclerosis
Our Friend in the Battle Against Osteoporosis
By Julie Stachowiak, Ph.D., About.com
Updated: June 23, 2008
Along with vitamin B12 deficiencies, many of us with multiple sclerosis (MS) also have deficiencies in vitamin D. Perhaps you have heard that research is revealing that low vitamin D levels may have made us susceptible to MS. Even so, we still need to take vitamin D, even if we already have MS and prevention is no longer an option.
There is some speculation and tenuous support from tiny studies and animal research that vitamin D could help slow down the MS disease process. However, there is irrefutable, concrete evidence that we all need vitamin D to help prevent osteoporosis – that’s enough for me to get with the vitamin D program. I urge all of you to consider joining me.
Why Should People with MS Care About Vitamin D?The majority of people with MS have some degree of vitamin D deficiency. People who live in northern regions commonly have a vitamin D deficiency for 4 to 6 months of the year. Interestingly, relapses tend to happen more in the spring when vitamin D levels reach their lowest, as stores have been depleted.
What Is Vitamin D in MS for?Osteoporosis: Vitamin D deficiency leads to osteoporosis, which is also very common in people with MS. In a study of women with MS, the average bone density and vitamin D levels were much lower than a control group without MS. Forty percent of study participants reported that they got very little to no exposure to sunlight.
Help for the Immune System: Animal studies (using EAE, the experimental animal form of MS) show that vitamin D deficiency worsened severity of symptoms and supplementation helped reduce symptoms.
MS Prevention? I imagine for most people reading this, MS is already a done deal – a diagnosis has been made and it is too late for prevention. However, it is interesting that in the Nurses’ Health Study, women who took vitamin D supplements had a 40% lower risk of MS. It has also been well-documented that MS is geographically distributed in such a way as to indicate that people without adequate vitamin D exposures from the sun are at higher risk for developing MS.
How Does Vitamin D Work?Vitamin D helps with calcium absorption and works to prevent osteoporosis. Vitamin D also increases lymphocytes and reduces proinflammatory cytokines, meaning it works to reduce inflammation and possibly autoimmune activity.
How Effective Is It?Although it has been suggested by epidemiological studies that vitamin D deficiencies increase the risk of developing MS, there is really no strong evidence to indicate that supplementing with vitamin D in people that already have MS will have much of a benefit in terms of disease progression. One very small study (11 people) showed a reduction in relapse rate in participants taking a combination of magnesium, calcium and fish oil with high levels of vitamin D. Another small study failed to show any effect of vitamin D supplementation. There are currently some long-term trials in progress to look at the role of vitamin D in MS.
What is the Usual Dosage of Vitamin D/How Is It Taken?Vitamin D is a fat-soluble vitamin. It is naturally present in very few foods, which include:
- Eggs (naturally found in yolks)
- Liver
- Fatty fish, such as sardines, salmon, tuna, mackerel
- Some ready-to-eat cereals
- Milk and other dairy products
- Other “fortified” products, such as orange juice, soy milk, rice milk, bread and flour
Side Effects of Vitamin D
High doses of vitamin D (over 1,500 micrograms per day) should not be taken, as this can cause:
- High blood pressure
- Nausea and vomiting
- Fatigue
- Kidney damage
Vitamin D supplementation should be undertaken with caution or avoided in people with:
- Abnormal levels of calcium (hypercalcemia and hypocalcaemia)
- Kidney disease
- Sarcoidosis
- Hypoparathyroidism
Costs
Vitamin D is extremely inexpensive and should be included in a calcium supplement.
My Bottom Line:
Will I take a vitamin D supplement? Well, sure. Despite having heard this for years, it finally just sunk in that a calcium supplement without vitamin D is pretty useless for preventing osteoporosis. I’m going to rethink my calcium supplement and make sure that it contains at least 200 mcg of vitamin D per day. I’m also going to make sure that I get at least 15 minutes of exposure to sunlight a day – guess I’ll have to start having my morning coffee outside, before it gets too hot to justify staying in the sun for any amount of time.
Sources:
Schwarz S, Leweling H. Multiple sclerosis and nutrition. Multiple Sclerosis. 2005 Feb;11(1):24-32.
Bowling, Allen C. Complementary and Alternative Medicine and Multiple Sclerosis. 2nd ed. Demos Publishing: New York. 2007.
Bowling, Allen C. and Stewart, Tom. So, what’s new about Vitamin D? InsideMS. October-November 2006. 57-58.Source