A NEW study by Scottish researchers shows evidence that the neurological disease multiple sclerosis (MS) could be linked to a viral infection.

While Scotland has the highest prevalence of MS in the world, the exact factors which lead to its development still remain a mystery. A combination of hereditary and environmental factors are thought to be the likeliest explanation.

Clusters of MS have previously been noted in certain areas, including the Faroe Islands, Orkney and Shetland.

Researchers at Dundee University used a comprehensive register which recorded MS cases in Tayside over three decades to examine whether similar outbreaks would appear in a region where there was no prior knowledge of high incidences of the disease.

The study found peaks of MS occurring in both certain years and in geographical locations, which scientists claim supports the idea that a virus is involved in the development of MS.

Co-author Dr Peter Donnan, a senior lecturer in medical statistics at the university, said: "We were interested in whether there was any clustering of cases in time and [location].

"Nobody really knows what causes MS. It is a multifactorial condition and there are debates about the role of genetic susceptibility and certain childhood viral infection in those who are susceptible, along with unknown environmental factors.

"In some years there may be epidemics of viral infections and in some years you get less, so what we are looking to see is whether there are peaks in certain years and peaks in certain locations."

The study, which is published in this month's Multiple Sclerosis journal, found there were a total of 772 new cases of the disease.

Nearly three-quarters of those diagnosed were female and the average age of the onset of symptoms was 35.7 years.

Researchers found that there was a significant increase in cases between 1982 and 1995, with an annual incident rate of 8.2 per 100,000 population, compared to an overall average figure of 7.2 per 100,000. During the 30 years studied, cases also appeared to peak every two to three years.

In addition, there was an outbreak of cases during 19931995 in a location southwest of Perth, centred in the rural area of Auchterarder but also including part of central Perth.

During that time, the annual incident rate of cases there rose to 17.1 per 100,000 population.

Donnan said: "If a viral agent had a role in the development of MS, then you would expect clusters. If you just found that the number of cases was constant over time and areas, then that would tend to go against that hypothesis.

"What we concluded is that it demonstrated evidence consistent with a role for viral infectious agents in MS."

Further investigation, he added, would be needed to help explain why, for example, the incidence of MS appears to peak every three years.

"One possible explanation is that viral disease epidemics have a three-year cycle, " he said.

There are an estimated 10,500 people in Scotland with MS, the most common neurological disorder diagnosed among young adults. It attacks the central nervous system and usually strikes between the ages of 20 and 40 years.

Mark Hazelwood, director of the Multiple Sclerosis Society Scotland, said there had been suspicions that viruses have been involved in the development of MS for some time.

"There have been more than 20 different viruses researched over the past couple of decades, " he said. "Sadly there has not been anything which has been proved or disproved on the specific involvement of a particular virus.

"What this research does is that it shows evidence consistent with a possibility of a viral involvement, but it doesn't prove it and it really highlights the need for further research."

Hazelwood also revealed that, to help with such research, the charity is currently looking into the possibility of setting up a national database to record MS cases across Scotland.

"This study was only able to be done because Tayside has got the best records about the number of people who have got MS in an area, " he said.

"We are trying to establish a similar database which would go right across the Scottish population, so we can really look at MS in the Scottish population and start to understand why there is so much more here."

http://www.rednova.com/news/display/?id=209917&source=r_health

judith. duffy@sundayherald. com

Source: Sunday Herald

A NEW study by Scottish researchers shows evidence that the neurological disease multiple sclerosis (MS) could be linked to a viral infection.

While Scotland has the highest prevalence of MS in the world, the exact factors which lead to its development still remain a mystery. A combination of hereditary and environmental factors are thought to be the likeliest explanation.

Clusters of MS have previously been noted in certain areas, including the Faroe Islands, Orkney and Shetland.

Researchers at Dundee University used a comprehensive register which recorded MS cases in Tayside over three decades to examine whether similar outbreaks would appear in a region where there was no prior knowledge of high incidences of the disease.

The study found peaks of MS occurring in both certain years and in geographical locations, which scientists claim supports the idea that a virus is involved in the development of MS.

Co-author Dr Peter Donnan, a senior lecturer in medical statistics at the university, said: "We were interested in whether there was any clustering of cases in time and [location].

"Nobody really knows what causes MS. It is a multifactorial condition and there are debates about the role of genetic susceptibility and certain childhood viral infection in those who are susceptible, along with unknown environmental factors.

"In some years there may be epidemics of viral infections and in some years you get less, so what we are looking to see is whether there are peaks in certain years and peaks in certain locations."

The study, which is published in this month's Multiple Sclerosis journal, found there were a total of 772 new cases of the disease.

Nearly three-quarters of those diagnosed were female and the average age of the onset of symptoms was 35.7 years.

Researchers found that there was a significant increase in cases between 1982 and 1995, with an annual incident rate of 8.2 per 100,000 population, compared to an overall average figure of 7.2 per 100,000. During the 30 years studied, cases also appeared to peak every two to three years.

In addition, there was an outbreak of cases during 19931995 in a location southwest of Perth, centred in the rural area of Auchterarder but also including part of central Perth.

During that time, the annual incident rate of cases there rose to 17.1 per 100,000 population.

Donnan said: "If a viral agent had a role in the development of MS, then you would expect clusters. If you just found that the number of cases was constant over time and areas, then that would tend to go against that hypothesis.

"What we concluded is that it demonstrated evidence consistent with a role for viral infectious agents in MS."

Further investigation, he added, would be needed to help explain why, for example, the incidence of MS appears to peak every three years.

"One possible explanation is that viral disease epidemics have a three-year cycle, " he said.

There are an estimated 10,500 people in Scotland with MS, the most common neurological disorder diagnosed among young adults. It attacks the central nervous system and usually strikes between the ages of 20 and 40 years.

Mark Hazelwood, director of the Multiple Sclerosis Society Scotland, said there had been suspicions that viruses have been involved in the development of MS for some time.

"There have been more than 20 different viruses researched over the past couple of decades, " he said. "Sadly there has not been anything which has been proved or disproved on the specific involvement of a particular virus.

"What this research does is that it shows evidence consistent with a possibility of a viral involvement, but it doesn't prove it and it really highlights the need for further research."

Hazelwood also revealed that, to help with such research, the charity is currently looking into the possibility of setting up a national database to record MS cases across Scotland.

"This study was only able to be done because Tayside has got the best records about the number of people who have got MS in an area, " he said.

"We are trying to establish a similar database which would go right across the Scottish population, so we can really look at MS in the Scottish population and start to understand why there is so much more here."

judith. duffy@sundayherald. com

Source: Sunday Herald

http://www.rednova.com/news/display/?id=209917&source=r_health

Matthew Herper, 08.09.05, 2:17 PM ET

NEW YORK - Shares of Biogen Idec and Elan soared on Tuesday as the companies said they had completed part of a safety review of their multiple sclerosis drug Tysabri--a medicine that has been demanded by some patients since it was pulled by the companies in February.

But some doctors and analysts still say it is important to be cautious about the meaning of the safety review--especially since scientists are still combing through data testing Tysabri in Crohn's disease, a gastrointestinal disorder, and rheumatoid arthritis.

Biogen (nasdaq: BGEN - news - people ) and Elan (nyse: ELN - news - people ) have finished the safety review of the drug they began when they pulled it from the market on Feb. 28, after it was linked to a rare brain disorder. They've found no new cases of progressive multifocal leukoencephalopathy. In all, they say, there have been three confirmed cases of PML in Tysabri patients, two of them in subjects with multiple sclerosis and one in a subject with Crohn's disease. In all, 2,000 multiple sclerosis patients were included in the review.

"It's good news that there are no new cases," says Igor J. Koralnik, director of the HIV/Neurology Center at Harvard's Beth Israel Deaconess Medical Center and an expert on PML. "But it's not surprising because the medicine had been stopped."

As a scientist and a physician, Koralnik says, he would like to see all the data before drawing any conclusions about Tysabri's risks.

Two cases of PML that were reported in the press were not confirmed in the final review. Says Alex Hittle, an analyst at A.G. Edwards: "It's really a case of 'no news is good news.'"

Especially important is the fact that all three patients who had contracted PML were on other drugs aside from Tysabri. PML seems to occur when a dormant virus--called the JC virus--takes advantage of a weakened immune system. Tysabri is linked to the PML cases, but the MS patients were also taking Avonex, another Biogen drug. The PML patient with Crohn's had taken other drugs that suppress the immune system.

"I think the odds of it getting back to market are looking better and better," says Hittle. "It seems that it's a side effect that's associated with some additional impairment to the immune system," he says.However, earlier this year, many analysts expected Tysabri would take over the MS market, effectively sidelining competition from Teva (nasdaq: TEVA - news - people ) and Serono (nyse: SRA - news - people ). That, Hittle says, is unlikely to happen. The PML issue could make it, "a real medicine of last resort."

Biogen and Elan say that they are taking preliminary steps to restart clinical trials of Tysabri in MS, which could help further define the drug's benefits and risks. Executives on a conference call were optimistic that Tysabri might return to the market for some patients. "We're encouraged that it will be coming back to the market," said James Mullen, chief executive of Biogen Idec.

Despite Mullen's optimism, there is still room for doubt on Tysabri. On a conference call with analysts at Sanford C. Bernstein last week, Daniel Wynn, a multiple sclerosis investigator, said that most patients being evaluated for safety were not given spinal taps--the most conclusive test for PML and the virus that causes it. Based on today's conference call with the companies, Wynn appears to have been correct.

"I think they are being very cautious on their language," says Geoffrey Porges, the biotech analyst at Bernstein. "The companies have said that there are 'no new confirmed cases', not 'no new potential cases.'"

Porges says he would still like to know how many patients who did not have spinal taps had suspected cases of PML. "I think we are still several steps away from a final decision," Porges says, "but this is now set up for a showdown with the regulatory agencies with patients and the companies on one side and safety oversight and caution on the other side."


http://www.forbes.com/home_europe/technology/2005/08/09/drugs-biogen-tysabri-cx_mh_0809tysabri2.html

http://tinyurl.com/8lt8g

By SANDRA BLAKESLEE

Published: August 2, 2005

Dr. Anna Berti sits facing a patient whose paralyzed left arm rests in her lap next to her good right arm. "Can you raise your left arm?" Dr. Berti asks.

"Yes," the patient says.

The arm remains motionless. Dr. Berti tries again. "Are you raising your left arm?" she asks.

"Yes," the patient says. But the arm still does not move.

Dr. Berti, a neuroscientist at University of Turin in Italy, has had many such conversations with stroke patients who suffer from denial syndrome, a strange disorder in which paralyzed patients vehemently insist that they are not paralyzed.

This denial, Dr. Berti said, was long thought to be purely a psychological problem. "It was a reaction to a stroke: I am paralyzed, it is so horrible, I will deny it," she said.

But in a new study, Dr. Berti and her colleagues have shown that denial is not a problem of the mind. Rather, it is a neurological condition that occurs when specific brain regions are knocked out by a stroke.

Patients deny the paralysis because a closely related region of the brain that is still intact appears to tell them that their bodies are responding normally.

The study, published in the July 15 issue of Science, may also shed new light on the nature of consciousness. Self-awareness, the researchers say, is not located in a unique brain structure or mechanism, but instead is distributed in many parts of the brain. As a result, there are different kinds of awareness for functions like movement, vision, awareness of the body and the space around the body.

Dr. Christof Koch, a neuroscientist and expert on consciousness at the California Institute of Technology in Pasadena, said the research was also interesting because it helped answer a fundamental question, namely, "What gives me the feeling that I know I am moving my hand or feel that I move my hand?"

Denial, Dr. Berti said, is usually considered to be a subfeature of a more common neurological syndrome called neglect. In neglect, patients suffer a stroke in the right side of the brain that results in paralysis of the left side of the body. Damage is pronounced in a region toward the back of the brain where personal space around the body is literally mapped and encoded by cells.

Neglect patients ignore everything, including their paralyzed limbs, in the left side of space, Dr. Berti said. But if their attention is purposefully drawn to that space, they recognize that their arm is paralyzed. They do not deny their situation.

But because denial and neglect can occur independently, Dr. Berti said she decided to see if patients who exhibited denial showed different underlying brain pathology.

For the study, 30 stroke patients underwent anatomical brain scans to pinpoint the source of their brain damage. All were paralyzed on the left side. Twelve patients exhibited neglect. Another 17 showed neglect and denial. One patient displayed only denial.

By comparing brain images, the researchers hoped to subtract denial from neglect, to see where the disorder resides in brain circuitry. As expected, neglect frequently involved damage to a region toward the back of the brain called the parietal lobe, as well as to nearby structures. Damage was also seen below the brain's mantle, or cortex, in tissue called white matter.

But to the researchers' surprise, brain damage in the patients who displayed denial tended to occur in the front part of the brain, particularly in the circuits that control movements and the planning of movements and in a region that helps produce feelings about the body.

Dr. Berti said these regions appeared to work together to generate, plan and perceive actions. They also generate self-awareness of actions.

Denial seems to arise from the fact that in patients who display the disorder, a related brain area is less affected or unaffected, Dr. Berti said. Called the supplementary motor area, it is involved in the mental simulation of movements. When athletes close their eyes and imagine a golf swing or skiing motion, this part of the brain is activated.

When patients who display denial are asked to raise an arm or clap their hands, the region that imagines these movements produces a familiar pattern of brain activation, showing normal or close to normal function, Dr. Berti said.

But the regions that maintain awareness of movements and carry them out are not working. The conflict between these regions, she said, becomes overwhelming.

The sense of having moved is powerful but awareness is absent. The solution for the paralyzed patient is to confabulate. If prodded for hours, patients will make up stories to explain their lack of action, Dr. Berti said.

One man said his motionless arm did not belong to him. When it was placed in his right visual field, he insisted it was not his.

"Whose arm is it?" Dr. Berti asked.

"Yours," he said.

"Are you sure?" Dr. Berti persisted. "Look here, I only have two hands."

The patient replied: "What can I say? You have three wrists. You should have three hands."

http://www.nytimes.com/2005/08/02/science/02deni.html?ex=1124164800&en=86ee7ef49dcd3325&ei=5070

http://tinyurl.com/7tkvr

ROCHESTER, MN -- August 12, 2005 -- A Mayo Clinic study demonstrates that only those multiple sclerosis (MS) patients with evidence for antibody deposition or complement activation -- immune cells that can cause tissue destruction -- in their lesions are likely to respond to plasma exchange, a treatment for acute MS attacks.

This is the first evidence that differences in pathological subtypes of MS may predict response to treatment. The findings will be published in the Aug. 13 issue of The Lancet.

"The new findings may partly explain why some patients respond to a particular treatment and others do not," says Claudia Lucchinetti, MD, Mayo Clinic neurologist and the paper's senior and corresponding author. "The biological basis for the variable response to current MS treatments is not well understood. It may be that not all MS patients form lesions in the same way and therefore would not be expected to respond to a given treatment the same. Thus, MS treatments may need to be more individualized and tailored for different types of patients."

During plasma exchange treatment, the patient's blood is removed and the blood cells are mechanically separated from the fluid plasma. The patient's blood cells are then mixed with replacement plasma and the mixture is returned to the patient. Mayo Clinic MS experts including Moses Rodriguez, M.D., Brian Weinshenker, MD; and Mark Keegan, MD; previously found plasma exchange may help restore neurological function in approximately 45% of those experiencing sudden, severe MS attacks whose resulting disabilities did not respond to high doses of steroid treatment.

Dr. Keegan, first author of the study, points out that plasma exchange is a treatment for severe MS attacks when standard treatment with corticosteroids fails; it is not a treatment to suppress future attacks or to restore neurological function that has been absent for more than three months.

The study was conducted retrospectively in an attempt to unravel the "all or none" response Mayo Clinic MS experts had witnessed with plasma exchange treatment for acute attacks in 19 patients who at one point had undergone a brain biopsy in the course of their disease when the diagnosis of MS was still in question.

Patients were seen at Mayo Clinic, the University of Vermont or a European center, and all included in the study had severe disabilities, including paralysis and loss of speech, which failed to improve with standard anti-inflammatory steroid treatment.

Since tissue was already available on these patients, Dr. Lucchinetti and her team classified their lesions into four patterns based on the types of immune cells present and the pattern of myelin injury.

Previously, Dr. Lucchinetti and her European collaborators, Professors Hans Lassmann of the Brain Research Institute at the University of Vienna, Austria; and Wolfgang Bruck of the University of Gottingen, Germany; developed and described a classification system for MS patients by lesion type into patterns I, II, III and IV.

The investigators found that the 10 patients with pattern II MS lesions, which contain large quantities of immunoglobulin (proteins that serve as antibodies) and complement activation (the ability to combine with antibodies to destroy tissue), experienced moderate to marked improvement after treatment with plasma exchange. These patients experienced major gains in cerebral, motor, brain stem/cranial nerve, cerebellar and/or sensory function. Improvement began after an average of three days.

However, none of the MS patients with lesions typical of either patterns I or III, which lack evidence for antibody or complement activation, achieved such improvement.

The investigators postulate that only the pattern II MS patients' attacks responded to treatment because of the way in which plasma exchange works -- by removing disease-causing factors in the blood and plasma, such as antibodies and complement, which are only present in pattern II MS lesions.

The findings published in The Lancet validate a theory held by Drs. Lucchinetti, Lassmann and Bruck that there are distinct patterns of tissue injury in different MS patients -- that MS is not the same disease in all patients and therefore cannot be treated the same way in everyone.

"Our work suggests that the development of MS may vary from patient to patient," says Dr. Lucchinetti. "This recent data on the correlation of plasma exchange response to tissue pathology supports our hypothesis that different patterns of tissue damage in MS may require different treatment approaches."

However, brain biopsies such as those undergone by the patients studied are not routinely done in MS patients -- they are only performed when excluding another diagnosis such as tumor or infection, according to Dr. Lucchinetti. Therefore, she explains that it is necessary to identify specific markers, either from blood, DNA or MRI, which can distinguish between these four patterns without the need for a brain biopsy.

Dr. Lucchinetti is the principal investigator of the International MS Lesion Project, funded by the United States National Multiple Sclerosis Society since 2000. This project is focused on trying to identify clinical, MRI, blood or genetic markers of MS lesions which could be used to stratify MS patients into subgroups in order to better tailor their treatments to the ways in which their MS lesions are formed.


SOURCE: Mayo Clinic
http://www.docguide.com/news/content.nsf/news/8525697700573E188525705B005042B1?Open&id=48DDE4A73E09A969852568880078C249&count=10

Select a CategoryView all Multiple Sclerosis - Cognitive Issues in Multiple Sclerosis - Managing Multiple Sclerosis - Multiple Sclerosis Treatment - Personal Stories of Multiple Sclerosis - Understanding Multiple Sclerosis
Getting to Know MS Multiple sclerosis is a progressive disorder of the nervous system affecting an estimated 400,000 Americans. Join experts as they discuss how the disease affects the body and the ways it is diagnosed. Watch Video Read Transcript Treatment for MS: Where Are We Now? Multiple sclerosis is a life long disease. There is no cure yet, but there are effective treatments available to help slow the progression of the disease and control symptoms. Watch Video Read Transcript
Recent Videos 1. MS 101 2. Treatment for MS: Where Are We Now? 3. IV Medicines for MS: A New Age of Therapies 4. Sex and Intimacy in People Living with MS 5. Making a Plan for MS: Why Start Treatment? View Entire Video Library Recent Articles 1. Overtime Pill: The Rest is History? 2. The Sum is Equal to the Whole: Individualizing MS Treatment 3. MS Drug Suspended 4. Pot-pourri: Cannabis Preparations for Pain 5. Redefining Intimacy in People with Multiple Sclerosis View Entire Article Library http://wpxi_ibsys.healthology.com/focus_index.asp?SPG=HANIBST&b=wpxi_ibsys	Take a Free Interactive Course on Multiple Sclerosis For More Information -- Click here -- Did You Know? 1. Going into a hot tub or being exposed to hot weather can cause a temporary worsening of symptoms in people with MS 2. Neutralizing antibodies may develop while a person is on interferon therapy which may render the drug less effective. 3. Multiple sclerosis may cause sexual problems 4. Yoga or exercise may help a person living with multiple sclerosis feel better 5. Changing the temperature of your environment can help turn around some MS symptoms

Part of $30 million National MS Society promise 2010 initiative for targeted research -

The largest awards ever made for research aimed at protecting and reversing neurological damage and restoring function in people with multiple sclerosis (MS) are going to four teams in the U.S. and Europe, who will use $15.6 million from the National Multiple Sclerosis Society to lay the groundwork for clinical trials over the next five years. These awards are part of the National MS Society's Promise 2010 Campaign, a nationwide effort to raise at least $30 million for targeted areas of research and patient care that hold great potential in the fight to end the devastating effects of MS but which have so far been under-explored.

The teams are based at Johns Hopkins University, University of Wisconsin Madison, University of Cambridge and University College London, with other collaborators in Canada, Europe and the U.S.

"We're excited that these international 'dream teams' of leading scientists and physicians have accepted our challenge to develop the tools needed for conducting clinical trials aimed at protecting against and repairing nervous tissue damage in MS," said John R. Richert, MD, Vice President of Research & Clinical Programs at the National MS Society. "This is a new chapter in MS research and should serve as a springboard for translating basic lab findings into important new treatments for people with MS."

MS involves a misdirected immune attack against myelin, the coating on nerve fibers that speeds nerve signals, and also destroys the underlying nerve fiber itself, causing symptoms like numbness, blindness, cognitive dysfunction and paralysis. Recent progress in controlling immune system attacks, coupled with rapid advances in the neurosciences, have made nervous tissue repair and protection emergent areas of MS research, prompting the National MS Society's unprecedented investment.

The repair teams are taking multifaceted approaches to protecting brain tissues and finding ways to rebuild the central nervous system. The teams will meet regularly to help foster synergy and collaboration.

"Collaboration is critical to achieving our goals with these projects. We know that sharing ideas and key findings will get us to the finish line that much faster," Dr. Richert continued.

"Dream teams" Leading the Way

Neurologist Dr. Peter A. Calabresi (Johns Hopkins University) and collaborators are searching for better ways to detect and quantify tissue injury in MS and testing agents that may protect the nervous system from further damage.

The international team headed by Professor Charles ffrench-Constant (University of Cambridge, UK) is focusing on restoring myelin by identifying and amplifying natural repair factors in the brain and by attempting transplantation of replacement cells.

Dr. Gavin Giovannoni (University College London, UK) and collaborators are attempting to turn cells into vehicles that will deliver repair molecules to sites of injury in the brain, and screening molecules for their protective properties as a prelude to clinical testing.

Professor Ian D. Duncan (University of Wisconsin Madison) is leading a multidisciplinary team to develop better imaging technologies such as PET and MRI to visualize myelin and nerve fiber damage, and to detect its repair. They are also exploring repair cell transplantation techniques.

Promise 2010: Giving people living with MS a future to look forward to rather than a past to look back upon

To encourage innovative research into highly promising areas and to improve MS medical care, the National MS Society launched the Promise 2010 Campaign. This nationwide effort is fueled by nearly 50 local Society chapters who have committed to raise at least $30 million to fund the four targeted initiatives.

In addition to the repair initiative, these include the establishment of Pediatric MS Care Centers to improve care and propel research into childhood MS; the MS Lesion Project, an international pathology study seeking to map and understand the meaning of MS damage seen in the brain in order to develop better ways of treating people with MS; and the Sonya Slifka Longitudinal MS Study, a nationwide database to examine the impact of MS on people's lives.

For more information about the Promise 2010 Initiatives, go to our Web site: http://www.nationalmssociety.org and click on Research > About Research > Targeted Research (nationalmssociety.org/promise2010.asp).

ABOUT MULTIPLE SCLEROSIS

Every hour in the United States, someone new receives that frightening diagnosis: multiple sclerosis. MS is an unpredictable, often disabling disease of the central nervous system. Symptoms range from numbness and tingling to blindness and paralysis. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are giving hope to those affected by the disease. Most people with MS are diagnosed between the ages of 20 and 50, with more than twice as many women as men contracting the disease. MS affects more than 400,000 people in the U.S., and 2.5 million worldwide.

ABOUT THE NATIONAL MS SOCIETY

The mission of the National MS Society is to end the devastating effects of MS. Through its home office and 50-state network of chapters, the Society funds more MS research, offers more services to people with MS, provides more professional education, and advances more MS advocacy efforts than any other MS organization in the world. This is why we're here. For more information, call 1-800-FIGHT MS or visit http://nationalmssociety.org.

Arney Rosenblat
arney.rosenblat@nmss.org
212 476-0436
National Multiple Sclerosis Society
http://nationalmssociety.org

http://www.medicalnewstoday.com/medicalnews.php?newsid=28961

Contact: Ian Duncan
duncani@svm.vetmed.wisc.edu
608-263-9828
University of Wisconsin-Madison

MADISON -- In an effort to develop new techniques to repair and protect the nervous system in multiple sclerosis patients, including the use of human stem cells, the National Multiple Sclerosis Society has awarded $3.4 million to a team of University of Wisconsin-Madison scientists.

The group, led by School of Veterinary Medicine professor Ian D. Duncan, is developing cell transplant techniques that may one day be used to repair the damaged myelin -- the critical sheathing of nervous system fibers -- characteristic of the debilitating and unpredictable disease.

"It's all about myelin repair and protecting nerve fibers," says Duncan, an international authority on myelin and myelin-related diseases. "The goal is to translate bench research into clinical application."

Multiple sclerosis -- which affects an estimated 2.5 million people worldwide, 400,000 people in the United States and 10,000 in Wisconsin -- involves a misdirected attack by the immune system on myelin, the nerve fiber coating that speeds the signals of the central nervous system. Multiple sclerosis also destroys the underlying nerve fiber, causing symptoms such as numbness, blindness, cognitive dysfunction and paralysis.

An important part of the Wisconsin project, according to Duncan, will be efforts to direct human stem cells to become myelinating cells that could be used in transplants to repair the nervous system lesions characteristic of multiple sclerosis.

The project, Duncan adds, will also expand studies of the antibiotic minocycline, a drug that has shown potential for protecting nerve fibers and mitigating the debilitating symptoms of multiple sclerosis. Duncan's lab has already shown that the drug has anti-inflammatory properties in an animal model of MS.

The Wisconsin team, Duncan says, plans to deploy powerful, state-of-the-art imaging technologies, including magnetic resonance imaging (MRI) and Positron Emission Tomography (PET), to image lesions and how they respond to treatment.

The work to be funded by the new grant, part of a five-year, $30 million initiative by the National Multiple Sclerosis Society, is expected to lay the groundwork for clinical trials by refining cell transplant methods and the ability to image myelin and nerve fiber damage and cell repair at work. The new initiative, known as "Promise 2010," includes a pledge of $2 million in support from the Wisconsin chapter of the National Multiple Sclerosis Society.

"We're tremendously gratified by this level of support," Duncan said. "It's a step, we think, toward major clinical advances."

"This is a new chapter in MS research and should serve as a springboard for translating basic lab findings into important new treatments for people with MS," said John R. Richert, vice president of research and clinical programs for the National Multiple Sclerosis Society.

###

In addition to Duncan, UW-Madison team members include John O. Fleming, a professor of medical microbiology and neurology; Aaron Field, a professor of neurology and radiology; Su-Chun Zhang, a professor of anatomy and neurology; Andrew L. Alexander, a professor of medical physics and psychiatry; P. Charles Garell, a professor of neurological surgery; James E. Holden, a professor of medical physics and radiology; Mary Elizabeth Meyerand, a professor of medical physics and neurology; Thomas Cook, a senior scientist in biostatistics; Zsuzsa Fabry, a professor of pathology; Alex Converse, an assistant scientist at the Waisman Center; and Maria Nikodemova, an assistant scientist in medical sciences.

-- Terry Devitt (608) 262-8282, trdevitt@wisc.edu

http://www.eurekalert.org/pub_releases/2005-08/uow-md081005.php

$30 Million 'Promise 2010' Initiative Launched to Propel MS Research and Care
Wednesday August 10, 9:30 am ET
$15.6 Million Awarded for Nervous System Repair in MS -- largest amount in history to go to targeted MS research

NEW YORK, Aug. 10 /PRNewswire/ -- The largest awards ever made for research aimed at protecting and reversing neurological damage and restoring function in people with multiple sclerosis (MS) are going to four teams in the U.S. and Europe, who will use $15.6 million from the National Multiple Sclerosis Society to lay the groundwork for clinical trials over the next five years.

These awards are part of the National MS Society's Promise 2010 Campaign, a nationwide effort to raise at least $30 million for targeted areas of research and patient care that hold great potential in the fight to end the devastating effects of MS but which have so far been under-explored. The teams are based at Johns Hopkins University, University of Wisconsin Madison, University of Cambridge and University College London, with other collaborators in Canada, Europe and the U.S.

"We're excited that these international 'dream teams' of leading scientists and physicians have accepted our challenge to develop the tools needed for conducting clinical trials aimed at protecting against and repairing nervous tissue damage in MS," said John R. Richert, MD, Vice President of Research & Clinical Programs at the National MS Society. "This is a new chapter in MS research and should serve as a springboard for translating basic lab findings into important new treatments for people with MS."

MS involves a misdirected immune system attack against myelin, the coating on nerve fibers that speeds nerve signals, and also destroys the underlying nerve fiber itself, causing symptoms like numbness, blindness, cognitive dysfunction and paralysis. Recent progress in controlling immune attacks, coupled with rapid advances in the neurosciences, have made nervous tissue repair and protection emergent areas of MS research, prompting the National MS Society's unprecedented investment.

The repair teams are taking multifaceted approaches to protecting brain tissues and finding ways to rebuild the central nervous system. The teams will meet regularly to help foster synergy and collaboration. "Collaboration is critical to achieving our goals with these projects. We know that sharing ideas and key findings will get us to the finish line that much faster," Dr. Richert continued.

"Dream teams" Leading the Way

Neurologist Dr. Peter A. Calabresi (Johns Hopkins University) and collaborators are searching for better ways to detect and quantify tissue injury in MS and testing agents that may protect the nervous system from further damage.

The international team headed by Professor Charles ffrench-Constant (University of Cambridge, UK) is focusing on restoring myelin by identifying and amplifying natural repair factors in the brain and by attempting transplantation of replacement cells.

Dr. Gavin Giovannoni (University College London, UK) and collaborators are attempting to turn cells into vehicles that will deliver repair molecules to sites of injury in the brain, and screening molecules for their protective properties as a prelude to clinical testing.

Professor Ian D. Duncan (University of Wisconsin, Madison) is leading a multidisciplinary team to develop better imaging technologies such as PET and MRI to visualize myelin and nerve fiber damage, and to detect its repair. They are also exploring repair cell transplantation techniques.

Promise 2010: Giving people living with MS a future to look forward to rather than a past to look back upon

To encourage innovative research into highly promising areas and to improve MS medical care, the National MS Society launched the Promise 2010 Campaign. This nationwide effort is fueled by nearly 50 local Society chapters who have committed to raise at least $30 million to fund the four targeted initiatives.

In addition to the repair initiative, these include the establishment of Pediatric MS Care Centers to improve care and propel research into childhood MS; the MS Lesion Project, an international pathology study seeking to map and understand the meaning of MS damage seen in the brain in order to develop better ways of treating people with MS; and the Sonya Slifka Longitudinal MS Study, a nationwide database to examine the impact of MS on people's lives. To support the Promise 2010 Initiatives or for more information about them, go to our Web site: http://www.nationalmssociety.org and click on Research.

ABOUT MULTIPLE SCLEROSIS

Every hour in the United States, someone new receives that frightening diagnosis: multiple sclerosis. MS is an unpredictable, often disabling disease of the central nervous system. Symptoms range from numbness and tingling to blindness and paralysis. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are giving hope to those affected by the disease. Most people with MS are diagnosed between the ages of 20 and 50, with more than twice as many women as men contracting the disease. MS affects more than 400,000 people in the U.S., and 2.5 million worldwide.

ABOUT THE NATIONAL MS SOCIETY

The mission of the National MS Society is to end the devastating effects of MS. Through its home office and 50-state network of chapters, the Society funds more MS research, offers more services to people with MS, provides more professional education, and advances more MS advocacy efforts than any other MS organization in the world. This is why we're here. For more information, call 1-800-FIGHT MS or visit http://www.nationalmssociety.org.

Note to Journalists:

Web site contains details about each of the 4 new Nervous System Repair and Protection projects and other targeted initiatives http://www.nationalmssociety.org/Research-Targeted.asp.

Video and audio news release available:

To view either the video or audio news release issued on August 10, 2005 to accompany the announcement of the Promise 2010 Campaign, please contact Beverley Yehuda at MultiVu at (212) 782-2969.


Source: National Multiple Sclerosis Society

http://biz.yahoo.com/prnews/050810/new002.html?.v=22

Wednesday, August 10, 2005; Posted: 11:02 a.m. EDT (15:02 GMT)
Genetically engineered mice are helping researchers find cures for diseases.

SAN FRANCISCO, California (AP) -- They're being bred now by the millions, the mutants, created to carry the ghastliest of diseases for the benefit of the human race.

Since researchers published the mouse's entire genetic makeup in map form three years ago, increasingly exotic rodents are being created with relative ease.

There's the Schwarzenegger mouse -- injected with muscle-building genes. The marathon mouse, which never seems to tire. Researchers recently engineered some mice to be extremely addicted to nicotine, and others to be immune to scrapie, a close cousin to the brain-wasting mad cow disease. And scientists are in hot pursuit of a Methuselah mouse, able to cheat death long after its natural brethren meet their maker.

Millions of these and other mutant mice are routinely created now, by injecting disease-causing genes or "knocking out" genes in mouse embryos. Their decreasing cost and increasing availability is helping researchers in pursuit of all manner of disease cures.

Top researchers in the Parkinson's disease field, for example, were more excited by the dopamine-free "knock-out" mouse that Duke University researchers invented than the actual study they unveiled this week, which suggests that the club drug Ecstasy reversed Parkinson's-like effects in these particular bio-engineered mice.

Researchers first genetically engineered a mouse in 1980. But until recently, such creations were mostly scientific novelties.

That changed drastically after President Clinton announced the mapping of the human genome in 2000. That's because mice and men are nearly genetically identical, each possessing just a few hundred different genes out of a possible 25,000 or so. Cancer in mice is a lot like human cancer, for instance. Mice have become powerful, living research tools.

The number of mutant research mice has grown so dramatically in recent years that companies are now profiting by housing and breeding scientists' creations.

"Space is precious," said Terrence Fisher of Charles River Laboratories in Wilmington, Massachusetts, the nation's largest mutant mouse house. The publicly traded company breeds and cares for scientists' creations and markets their inventions to other researchers, shipping an estimated 7 million mice worldwide annually.

"The novelty of being simply able to do this has worn off and clearly these mice are tools that are accelerating research," Fisher said.

The repository with the country's widest selection of mutant mice is the nonprofit Jackson Laboratory in Bar Harbor, Maine, where most researchers who genetically engineer mice with government money are required to send some of their mice.

The lab boasts a collection of nearly 3,000 different mutant mice types and shipped 2 million animals to U.S. researchers last year. The mice are in such great demand that Jackson opened another breeding facility in West Sacramento, California four years ago. "We have always been the mouse place," said Jackson spokeswoman Joyce Peterson.

The lab charges researchers $11 for mice that are particularly useful in diabetes work and as much as $200 each for so-called nude mice, which lack immune systems. These mice -- think "boy in the bubble" -- are bred and kept in sterile rooms, high-technology cages and their human handlers are required to shower each time they enter and leave.

The Jackson Laboratory's main focus is cancer research, but the mice business accounts for $60 million annually, Peterson says.

Many animal rights groups oppose all animal experimentation as cruel, but lab scientists who work with bio-engineered mice are quick to point out that the Food and Drug Administration requires that all drugs be tested on animals before people. Peterson said the Jackson lab, in operation since 1929, follows federal guidelines on animal treatment and has never been targeted by anti-experimentation militants.

Nearly all the genetically engineered mice in circulation today have but one gene added, subtracted or altered. The problem with that model is that many diseases such as diabetes and cancer are caused by multiple gene malfunctions.

"Eventually, that's where engineered mice are going," said Mendell Rimer, a University of Texas neuroscientist who tends to about 500 mice in his Austin lab. "That's a more realistic disease model."

Rimer said such multiple gene engineering is occurring in tiny worms, and it's only a matter of time before researchers report similar success in mice.

Rimer's genetically engineered mice are among the most advanced, and offer a glimpse of the breakthroughs to come.

He spent 2 1/2 half years engineering mice with muscles that lose connection to their nerve cells. He's done this by splicing into mice a cancer gene which creates a protein that "disassembles" the connections. But he's also taken his work one step further than the usual cut-and-paste work.

Rimer is able to turn on the mutant gene by feeding the genetically engineered mouse an antibiotic. He can turn it off by stopping the antibiotic treatment. This way, he can observe the progression and regression of the mutation he made, giving him unparalleled insight into how nerves communicate with the muscle.

"We can control the timing of the defect that we induce in these mice," Rimer said. "This type of complexity is where genetic engineering is heading."

http://www.cnn.com/2005/TECH/science/08/10/lab.mice.ap/index.html

http://tinyurl.com/ax2pd
By TSC Staff
8/9/2005 8:10 AM EDT

Two star-crossed biotech companies took a step toward redemption Tuesday.

Biogen (BIIB:Nasdaq - commentary - research) and Elan (ELN:NYSE - commentary - research) announced that a safety review of patients taking their drug Tysabri for multiple sclerosis found no new cases of the rare brain disease progressive multifocal leukoencephalopathy.

Tysabri was pulled from the market in February after being linked to the disease, which is known by the abbreviation PML. The companies subsequently confirmed three cases of PML, two of which were fatal (and one of which occurred in a patient taking the drug for something other than multiple sclerosis: Crohn's disease.)

The withdrawal, which decimated both companies' stocks, prompted a broad safety review both of patients taking Tysabri in clinical trials and those who had used it under doctor's prescriptions. On Tuesday, Biogen and Elan said about 1,800 patients in clinical trials participated in a safety evaluation, with no new cases of PML discovered.

"Given the high unmet medical need in MS and the therapeutic benefit we have seen with Tysabri, we are encouraged by these safety findings," the companies said. "We look forward to working with regulatory authorities to determine the path forward for Tysabri."

In premarket Instinet trading, shares of Biogen were up 6.8% to $41.03, while Elan rose 19% to $9.52.

According to the companies, an ongoing safety evaluation of Tysabri in Crohn's disease and rheumatoid arthritis should be completed by the end of the summer.

Biogen and Elan said they're "taking preliminary steps to restart clinical trials in MS."

http://www.thestreet.com/_googlen/stocks/biotech/10237179.html?cm_ven=GOOGLEN&cm_cat=FREE&cm_ite=NA

http://tinyurl.com/8zwae

Additional Data Needed for MS Diagnosis
Two or more attacks; objective clinical evidence of 2 or more lesions None(a)
Two or more attacks; objective clinical evidence of 1 lesion

Dissemination in space demonstrated by:

* MRI(b), or
* 2 or more MRI lesions consistent with MS plus positive CSF(c), or
* await further clinical attack implicating a different site.

One attack; objective clinical evidence of 2 or more lesions

Dissemination in time demonstrated by:

* MRI(b), or
* second clinical attack.

One attack; objective clinical evidence of 1 lesion (clincally isolated syndrome)

Dissemination in space demonstrated by:

* MRI(b), or
* 2 or more MRI lesions consistent with MS plus positive CSF(c)

And dissemination in time, demonstrated by:

* MRI(b), or
* Second clinical attack

Insidious neurological progression suggestive of MS

Positive CSF(c), and dissemination in space,
demonstrated by:

* 1) 9 or more T2 lesions in brain, or 2) 2 or more lesions in spinal cord, or 3) 4-8 brain lesions plus 1 spinal cord lesion; or
* Abnormal visual evoked potentials with MRI demonstrating 4-8 brain lesions, or fewer than 4 brain lesions plus 1 spinal cord lesion; and

* Dissemination in time demonstrated by MRI(b); or
* Continued progression for 1 year

(a) Brain MRI is recommended to exclude other etiologies
(b) MRI criteria for dissemination in space or time are described in Table 2
(c) Positive CSF defined as oligoclonal bands different from those in serum, or raised IgG index.
Adapted from reference 6.
Copyright 2002 The Cleveland Clinic Foundation

Return to Multiple Sclerosis Chapter

http://www.clevelandclinicmeded.com/diseasemanagement/neurology/multsclerosis/table1ms.htm

PORTLAND, Ore. -- Oregon Health & Science University researchers have identified some of the key factors that prevent the repair of brain damage caused by multiple sclerosis (MS), complications of premature birth, and other diseases and conditions. The findings offer important clues about why the nervous system fails to repair itself and suggest ways that at least some forms of brain damage could be reversed. The research is published in the August edition of the scientific journal Nature Medicine.

"For many years, scientists have understood that damage to the insulation-like sheath surrounding nerve cells in the brain, called myelin, is part of the disease process for MS and other brain disorders," said Larry Sherman, Ph.D., an associate scientist in the Division of Neuroscience at the Oregon National Primate Research Center and an adjunct associate professor of cell and developmental biology in the OHSU School of Medicine. "In recent years, it became clear that there were cells at the sites of this damage that should have the capacity to repair the brain and spinal cord but they fail to do so. Our studies have revealed that there is a particular signal in the damaged brain that prevents these cells from restoring lost myelin. We're hopeful that we can develop methods to counteract this process in animal models in our search for human treatments."

Other key OHSU researchers involved in the study are: Stephen Back, M.D., Ph.D., an associate professor of pediatrics and neurology in the OHSU School of Medicine; and Bruce Bebo Jr., Ph.D., a scientist in the OHSU Neurological Sciences Institute and an associate professor of neurology in the OHSU School of Medicine.

The researchers decided to collaborate following a key finding in Sherman's lab where scientists were studying a mouse model for tumors in the central nervous system. The mice had been bred to overproduce a protein which had been implicated previously in tumor formation. The protein, called CD44, is frequently found in limited amounts in the brains of both healthy mice and humans. However, instead of developing tumors, the mice with elevated CD44 developed tremors similar to those seen in individuals with multiple sclerosis (MS).

Further investigation revealed that the tremors were associated with the loss of myelin sheaths on nerve cells, very similar to the myelin loss associated with MS and other neurological diseases, as well as in premature infants. In addition, Sherman's lab found large amounts of hyaluronic acid (HA), a carbohydrate, in the brains of these mice. A comparison to brain tissue of deceased human MS patients also revealed heightened levels of HA, apparently caused by the increased presence of CD44 -- something which had never been noted before. It was at this point that Sherman contacted Bebo, who had been studying an MS-like disease in mice for many years, and they began a collaboration to study how HA accumulated in regions of the nervous system where myelin had been destroyed.

"These investigations revealed that oligodendrocytes, which are cells that form myelin in the brain, were prevented from repairing the damaged myelin when there were elevated levels of HA," explained Bebo. "By studying another mouse model in my lab, we made the connection between heightened levels of HA -- specifically a high-molecular weight version of HA -- and myelin loss in an MS-like disease in mice. We also identified the cells that were making the HA and determined that HA accumulation was linked to an overabundance of the CD44 protein."

To further understand the process, Bebo and Sherman joined forces with Back, a pediatric neurologist and researcher studying developmental brain injury in premature infants. Previous research by Back and other scientists had revealed a link between the white matter brain damage associated with premature birth and damage to immature cells in the brain and spinal cord, called oligodendrocyte progenitors. These precursor cells give rise to all of the mature oligodendrocytes that make myelin throughout life.

Back's lab provided the team with tissue cultures of immature rat oligodendrocytes. The researchers then applied HA to these cells which indeed kept the immature cells from maturing into myelin-producing cells. In another key experiment, Sherman and Back confirmed in another animal model of MS that injection of the HA into damaged myelin prevented myelin from reforming where it had already been destroyed. Conversely, they showed that reducing HA levels or making the HA inactive allows myelin to once again form.

"It is our hope that we can interfere with this disease process at one or multiple stages," explained Back. "Of course for those already battling a myelin-destroying disease, you would want to try and promote the return of myelin-forming cells. This general area of research is of particular interest to me in my attempts to counteract the white matter brain damage that is often associated with premature birth and can lead to a form of cerebral palsy (CP). Our early findings have shown that scar tissue in the brains of premature infants who die during intensive care also produces HA. We believe the HA may also prevent the production of myelin-producing cells and be related to the motor impairment seen in CP. My hope is that this work will benefit a wide range of patients from premature infants to stroke victims to those suffering from debilitating neurological diseases such as MS where repair of damaged myelin does not occur."

Sherman shares this hope. "This discovery has revealed a target for therapies and opens the door to the exciting possibility that we may, one day, be able to not only stop disease progression but also repair damage that is already there. The future efforts of our three labs will be aimed at exactly that goal. "

"The work of these investigators offers new hope to people with MS and their families," said National MS Society Oregon Chapter President Graham McReynolds. "Treatments and nerve repair research that once seemed decades away may now be within our grasp. This is a time of great promise for MS research."

"Preterm birth can interrupt the normal myelination process. Therefore, this report may help to explain the brain damage seen in premature infants, some of whom develop cerebral palsy," said Michael Katz, M.D., senior vice president for research and global programs at the March of Dimes, which supported Dr. Back's research. "More than 470,000 babies are born prematurely each year. Until we find the answers to preventing prematurity, research such as this may lead us to new ways to prevent brain damage and has the potential to improve the lives of thousands of infants. "

Additional collaborative research took place in the laboratory of Mahendra Rao at the National Institute on Aging, a component of the National Institutes of Health; and in the laboratory of Bruce Trapp at the Lerner Research Institute at The Cleveland Clinic.

###

Funding for this research was provided by the National Multiple Sclerosis Society; the March of Dimes Birth Defects Foundation; and the National Institute of Neurological Disorders and Stroke and the National Institute of Environmental Health Sciences, both of which are branches of the National Institutes of Health.

OHSU includes the schools of dentistry, medicine, nursing and science and engineering; OHSU Hospital and Doernbecher Children's Hospital; numerous primary care and specialty clinics; multiple research institutes; and several outreach and community service units.

The ONPRC is a registered research institution, inspected regularly by the United States Department of Agriculture. It operates in compliance with the Animal Welfare Act and has an assurance of regulatory compliance on file with the National Institutes of Health. The ONPRC also participates in the voluntary accreditation program overseen by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC).

http://www.eurekalert.org/pub_releases/2005-08/ohs-ord080505.php

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• About Multiple Sclerosis - Discover insight into MS treatment, research, and resources with guide Sarah Beaubien.
• Accelerated Cure Project for Multiple Sclerosis - National nonprofit dedicated to curing Multiple Sclerosis by determining its causes.
• All About Multiple Sclerosis - Provides a description, news, glossary, and a list of famous people with MS.
• The Brain Matters: Multiple Sclerosis - Causes and symptoms, how it is diagnosed, treatment options, and living with the disorder.
• Cybercafe - Breaking the Isolation - European Cybercafes aim to provide information and a means of communication.
• DIRECT-MS - Provides information on the relationship between multiple sclerosis and diet.
• eMedicine Health - Multiple Sclerosis - Consumer health resource center providing an overview of symptoms and treatment.
• General Practice Notebook - Multiple Sclerosis - Clinically-oriented information.
• Healthology Multiple Sclerosis Focus - A comprehensive resource for patients and families living with multiple sclerosis.
• HealthTalk Multiple Sclerosis Education Network - Treatment information and resources presented by leading multiple sclerosis experts.
• The History Of MS - Flash exhibition shows historical milestones of the disease.
• InteliHealth: Multiple Sclerosis - Presents basic information, treatment options, current research and an ask-the-expert section.
• International Journal of MS Care - Publication of the Consortium of Multiple Sclerosis Centers and Rehabilitation in Multiple Sclerosis.
• Learn About MS - San Francisco Bay Area nurse gives MS information in your home.
• Making Waves - Find a guide to Multiple Sclerosis (MS) with information about possible causes, diagnosis, treatment and coping with the disease.
• Mayo Clinic: Multiple Sclerosis - Symptoms, causes, risk factors, diagnosis, treatment and methods of self-care.
• McFox's Multiple Sclerosis Pages - Information site with lifestyle suggestions,computer advice, and news on MS.
• MerckSource - Multiple Sclerosis - Provides information and diagrams about multiple sclerosis.
• MossRehab ResourceNet - Multiple Sclerosis - Information and resources to improve the activities of daily living for MS patients.
• MS Active Source - Information about the diagnosis and treatment as well as a list of support groups throughout the UK and Ireland.
• MS Crossroads - Information and links for patients, doctors and researchers.
• MS Leaders - A peer-to-peer forum for the MS professional community.
• MS Means...Multiple Sclerosis - Information and support with a special emphasis on sexuality.
• MS Quarterly Report - Publication of Eastern Paralyzed Veterans Association and the CMSC/North American Research Committee on MS.
• MS Support WebRing - Sites with personal stories, MS information and support.
• MS-Gateway - Looks at forms of the disease, treatments for it, and lifestyle adjustments. Multi-lingual.
• MSnet - Descriptions of typical symptoms, the definition , and personal stories. List of MS Clinics.
• MS-Network - News,interviews with patients, care-partners, and treatment information.
• The MSplus Foundation - Information and support for persons who have multiple sclerosis, plus have been diagnosed with cancer.
• Multiple Sclerosis - An information portal for MS including diagnosis, medication and holistic therapy treatments.
• Multiple Sclerosis : University of Utah - For medical students and physicians in training.Useful for others as well.
• Multiple Sclerosis Alternatives Webring - Sites from around the world that deal with alternative approaches to treating multiple sclerosis.
• Multiple Sclerosis Library - Complete library on research, treatment, clinical trials, symptoms, and medications.
• Multiple Sclerosis National Research Institute - MS news and research. Lists symptoms.
• Multiple Sclerosis News - Topix.net - News on multiple sclerosis collected from diverse sources on the web.
• Multiple Sclerosis Resource Center - Presents articles, medical news, video updates, message boards and chat rooms,and a resource directory.
• Multiple Sclerosis South Africa - Information on MS, its effects and tips to help you cope.
• New York Online Access to Health (NOAH): Multiple Sclerosis - A directory to resources on various topics relaiting to MS.
• NINDS Multiple Sclerosis Information Page - National Institute of Neurological Disorders and Stroke information and links to related organizations.
• Schilder's Disease - A variant of MS.
• This is MS - Provides news, research and a interactive community.
• Understanding MS - Articles and webcasts by medical doctors.
• WebMD Health - Consumer health site's MS section.

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http://dmoz.com/Health/Conditions_and_Diseases/Neurological_Disorders/Demyelinating_Diseases/Multiple_Sclerosis/

by John C. Martin
Article Date: 08-05-05

Medical experts have theorized in recent years that the cause of multiple sclerosis may be connected to a viral infection in the body.1-3 Now, a new analysis from doctors at Harvard Medical School suggests that high levels of antibodies that target and attack the Epstein-Barr virus may be the culprit in MS.4

Ubiquitous Virus
Epstein-Barr virus (EBV) is one of the most common human viruses, and is responsible for infectious mononucleosis in adolescence or early adulthood in up to 50% of cases. In the United States, an overwhelming 95 percent of people between the ages of 35 and 40 have been infected with the virus at least once in their lives. Infants become susceptible to the virus as soon as maternal antibody protection disappears after birth, and children can also become infected, albeit symptoms are usually hidden or are indistinguishable from those of other common childhood ailments.5

Association Between Age and MS Risk
The latest study suggesting a link between EBV and multiple sclerosis was actually a revised version of an original paper published in the Journal of the American Medical Association two years ago.6 Due to an error in the processing of the study data, the authors retracted the original article and published the revised report in the May 26 issue of the journal.

While the latest study still found a relationship between EBV antibodies and the risk of developing MS, the investigators reported that the association was dependent on a patient's age.

"Anti-EBV antibodies are elevated in individuals with multiple sclerosis, and a premorbid increase has been reported in two studies," wrote Alberto Ascherio, MD, DrPH, of Harvard Medical School, and his colleagues. "But both relied on a single blood sample from each study participant. We, therefore, conducted a larger prospective investigation using serial blood samples collected several years before onset of MS."

The new study prospectively followed 83 patients diagnosed with MS among 3 million military personnel granted temporary or permanent disability due to their illness, and whose blood samples had been stored by the Department of Defense.

Hunting for a Virus
For each of these patients, the researchers identified the earliest available blood sample, plus up to two additional samples collected before MS onset, as well as the first samples collected after MS appeared. The average time between the first blood sample collected and the onset of the disease was four years, the researchers reported.

The researchers then searched for levels of antibodies to EBV in the blood samples collected. They were compared to levels of antibodies against another type of virus. The blood samples from MS patients were also compared with blood samples collected from people without multiple sclerosis.

EBV Link with MS Uncovered
Ascherio and his colleagues found that average antibody levels relative to EBV infection were "significantly higher" among those who later developed MS compared to those without MS, or compared to levels of antibodies against the other virus examined. They also noted that the risk of developing MS increased with increasing levels of these antibodies to EBV. A four-fold increase in the antibody levels was associated with a three-fold increased risk of developing the disease, they wrote.

Next, the researchers wanted to know if levels of EBV antibodies changed with age, given the fact that MS incidence "increases sharply between the ages of 20 and 30 years."

The investigators found that among those who developed MS, antibody levels increased sharply in early adulthood, and then plateaued. In those under age 20, antibody levels were similar to those in patients without MS. But the levels jumped two-to-three-fold by age 25, the researchers reported.

This finding was "striking and unexpected," the research group wrote. "The fact that this increase occurred between the late teens and the mid-to-late 20s, independently from the age of MS onset, supports the hypothesis of an age of vulnerability of the acquisition of MS," the investigators wrote.

While these "modest increases with age" for EBV antibody levels were seen in those patients who later developed MS, the same trend wasn't seen in antibodies against the other virus measured in the study.

In conclusion, the findings suggest that increased levels of antibodies to EBV is not a consequence of MS, but may instead be an early step in the progression of the disease, Ascherio and his team wrote. Further, other studies have linked infection with EBV with an increased risk of lupus,7 "suggesting that EBV may be a risk factor for autoimmune diseases."

1. Haahr S, Sommerlund M, Moller-Larsen A, Mogensen S, Andersen HM. Is multiple sclerosis caused by a dual infection with retrovirus and Epstein-Barr virus? Neuroepidemiology 1992;11(4-6):299-303.
2. Influence of JC virus coding region genotype on risk of multiple sclerosis and progressive multifocal leukoencephalopathy. J Neuroviral 2000 May;6 Suppl 2:S101-8.
3. Kriesel JD, White A, Hayden FG, Spruance SL, Petajan J. Multiple sclerosis attacks are associated with picornavirus infections. Mult Scler 2004 Apr;10(2):145-8.
4. Levin LI, Munger KL Rubertone MV et al. Temporal relationship between elevation of Epstein-Barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis. JAMA 2005 May 25;293(20):2496-500.
5. Centers for Disease Control and Prevention (CDC). Epstein-Barr Virus and Infectious Mononucleosis. Available at: http://www.cdc.gov/ncidod/diseases/ebv.htm. Accessed July 29, 2005.
6. Levin LI, Munger KL, Rubertone MV et al. Multiple sclerosis and Epstein-Barr virus. JAMA 2003 Mar 26;289(12):1533-6.
7. Parks CG, Cooper GS, Hudson LL et al. Association of Epstein-Barr virus with systemic lupus erythematosus: effect modification by race, age, and cytotoxic lymphocyte-associated antigen 4 genotype. Arthritis Rheum 2005 Apr;52(4):1148-59.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.

http://www.msneighborhood.com/content/in_the_news/archive_2258.aspx

Friday, August 05, 2005 11:00 IST
California

MediciNova, Inc., has started enrolment of patients in a Phase II clinical study with MN-166 for the treatment of multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. MN-166 is an orally administered drug with a novel mechanism of action that includes the inhibition of phosphodiesterase IV.

Under a licensing agreement with Kyorin Pharmaceutical Co. Ltd. of Tokyo, Japan, MediciNova obtained exclusive worldwide rights, except for Japan, China, Taiwan and South Korea, to develop and commercialize MN-166 for multiple sclerosis. For the past 16 years, MN-166 has been marketed in Japan as Ketas (ibudilast), for the treatment of asthma and cerebrovascular disorders. Ibudilast was also launched in Korea in September 2002.

"MN-166 may represent a significant advance in the treatment of relapsing-remitting MS," Richard Gammans, chief development officer at MediciNova said adding, "In small, open label studies in patients with relapsing-remitting MS, MN-166 produced some rather encouraging activity. This Phase II study is being conducted in nine countries in Eastern Europe and will compare two oral doses of MN-166 to placebo in 300 patients with relapsing-remitting MS."

The study will measure reduction in MS lesions in the brain as detected by MRI (magnetic resonance imaging), reductions in annualized relapse rates and functional status as determined by the EDSS (Expanded Disability Status Scale), according to a company release.

http://www.pharmabiz.com/article/detnews.asp?articleid=28825&sectionid=