Exciting Breakthroughs in Medical Research :MS, Autoimmune

GULF WAR VETERANS WITH AUTOIMMUNE DISORDERS/MS/Myelin Problems/Diabetes/Arthritis/Immune Disorder-Research Updates

Breaking NEWS on Multiple Sclerosis  IMPORTANT RESEARCH

Exciting news from Italy. I believe everyone should take notice of latest findings of (originally) Dr. Zamboni from Italy.  Findings have been published in medical magazines,a dedicated international congress in Bologna was organized this month and attended by international medical researchers including from USA.

In short his thesis is, that MS is caused by venous stenosis which can be diagnosed with modern imaging technology such as doppler ultrasound and MRI (MRA/MRV). All MS patients investigated show the abnormality contrary to healhty patiens.
An interesting demonstration illustrating the principle can be seen on YouTube:  http://www.youtube. com/watch? v=yGFe-3h26Vs

As soon as we locate the Peer Reviewed Material or Medical Journal that discusses this finding we will post it here on VT.

Other Research over last several months for MS, Immune System, Arthritis, Myelin Sheath of Spinal Cord, and Diabetic Peripheral Problems is included in this article below.

Notice to Department of Veterans Affairs:  These updates need to be passed on to Gulf War Veterans and other Veteran Cohort Groups.  These updates need to get to all Medical Professionals within the VA.

WE need the registries for Diagnosed Illnesses for Gulf War 90-91 Veterans Now we urge the Veterans Affairs Department to BE Proactive and Make it Happen!

Scientists Discover New Clues About How The Immune System Works
Main Category: Immune System / Vaccines
Also Included In: Multiple Sclerosis
Article Date: 16 Sep 2009 – 8:00 PDT

British researchers have made a new discovery about how the immune system works.

The findings, published in the journal Nature Immunology, looked at a specific subset of immune cells called Natural Killer (NK) cells.  NK cells are specialised immune cells that play a role in killing and removing infected or unhealthy cells, which include cancerous cells.

They are known to be involved in preventing cancer, but their involvement in multiple sclerosis (MS) is less clear. Some studies suggest that they may dampen down the activity of other immune cells thought to be involved in the damage to myelin caused in MS.

Dr Susan Kohlhaas, Research Communications Officer at the MS Society, said: "This research has increased our basic understanding of how the immune system works, which is a good thing. She added: "It is still unclear how this finding will directly apply to MS and that is the next step in determining the value of this research to people with MS."

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Early Research Holds Promise For New Therapies And Better Prediction Of Patient Outcomes In Multiple Sclerosis
Main Category: Multiple Sclerosis
Also Included In: Genetics;  Biology / Biochemistry
Article Date: 14 Sep 2009 – 0:00 PDT

A Mayo Clinic study has found that two genes in mice were associated with good central nervous system repair in multiple sclerosis (MS). These findings give researchers new hope for developing more effective therapies for patients with MS and for predicting MS patients’ outcomes. This study was presented at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis in Dusseldorf, Germany, on Sept. 11, 2009.

"Most MS genetic studies have looked at disease susceptibility — or why some people get MS and others do not," says Allan Bieber, Ph.D., a Mayo Clinic neuroscientist and author of this study. "This study asked, among those who have MS, why do some do well with the disease while others do poorly, and what might be the genetic determinants of this difference in outcome."

Mayo Clinic provides care for nearly 2,500 patients with MS each year. MS is a disease of the central nervous system that includes the brain, spinal cord and nerves. MS is called a demyelinating disease because it results from damage to myelin, the insulating covering of nerves. It occurs most commonly in those between the ages of 20 and 40, and is the most frequent neurological disorder in young adults in North America and Europe. Approximately 330,000 people in the United States have MS.  Symptoms include loss of muscle coordination, strength, vision, balance and cognition.

Dr. Bieber and a team of Mayo Clinic researchers used two different strains of mice with a chronic, progressive MS-like disease. One strain progressed to paralysis and death. The other underwent the initial damage induction phase of the disease and then spontaneously repaired the damage to the central nervous system and retained most neurologic function. Using the powerful genetic mapping techniques that are available for mice, the team mapped two strong genetic determinants of good disease outcome.

"It’s possible that the identification of these genes may provide the first important clue as to why some patients with MS do well, while others do not," says Dr. Bieber. "The genetic data indicates that good central nervous system repair results from stimulation of one genetic pathway and inhibition of another genetic pathway. While we’re still in the early stages of this research, it could eventually lead to the development of useful therapies that stimulate or inhibit these genetic pathways in patients with MS."

According to Dr. Bieber, the research suggests that there may be a small number of strong genetic determinants for central nervous system repair following demyelinating disease, rather than a larger number of weak determinants.  "If that’s true, it may be possible to map the most important genetic determinants of central nervous system repair in patients with MS and define a reparative genotype that could predict patients’ outcomes," says Moses Rodriguez, M.D., a Mayo

Clinic neurologist and director of Mayo Clinic’s Center for Multiple Sclerosis and Central Nervous System Demyelinating Diseases Research and Therapeutics. "Such a diagnostic tool would be a great benefit to patients with MS and is consistent with the concepts of ‘individualized medicine.’" Also on the Mayo Clinic research team was Kanitta Suwansrinon, M.D.

Source:
Elizabeth Rice
Mayo Clinic

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Blood Test May Predict Course Of MS
Main Category: Multiple Sclerosis
Also Included In: Blood / Hematology
Article Date: 01 Sep 2009 – 1:00 PDT

Scientists have discovered a blood test that could predict the course of multiple sclerosis (MS), or even indicate who is likely to develop the condition after a first MS-like attack.

The results of the study suggest that differing antibody levels produced in response to the common virus Epstein Barr Virus (EBV), may predict the course of MS.

If proven in further studies, this would be the first credible biological indicator, or biomarker, identified for MS that could predict disability progression from a simple blood test.

The innovative work was carried out at the Institute of Neurology, UCL and the Institute of Cell and Molecular Biology, Barts and The London and was funded by the MS Society.

It is hoped the findings will aid the development of better ways to predict who goes on to develop MS after initial MS-like symptoms and help in identifying more effective therapies for the 100,000 people living with MS in the UK.

The paper’s lead author, Clinical Research Fellow Dr Rachel Farrell, said: "All the participants in our study had previous history of infection with EBV, which has been shown in other studies and is not surprising given that a large majority of the adult population is infected with EBV.

"What was surprising is that the levels of a molecule in the blood called anti-EBNA-1 IgG, induced by the virus, were associated with the activity of MS. "The results of this work show that those participants who had new areas of MS damage in the brain also had high levels of the anti-EBNA-1 IgG molecule in their blood."

The researchers received funding of nearly £35,000 from the MS Society’s Innovation Research grant scheme. The authors of the study, published in the journal Neurology, concluded that anti-EBNA-1 IgG is a potential biomarker in MS that might be useful in predicting disability and progression. They added that the work needed to be validated in larger studies and in combination with other as yet unidentified biomarkers.

Dr Susan Kohlhaas, Research Communications Officer at the MS Society, said: "We’re delighted that such an interesting study has produced these valuable results that will give scientists a new avenue of MS research to explore. "Identifying biomarkers of MS is a key area of research and this work is a stepping stone on the path to mapping out the course of the condition and potentially determining prognosis.  "People with MS find the uncertainty of what the future holds very daunting so more knowledge about what might lie in store could be a big help."

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Multiple Sclerosis: National Search For Proteins That Cause MS
Main Category: Multiple Sclerosis
Article Date: 26 Aug 2009 – 4:00 PDT

Australian researchers will aim to discover the proteins that cause multiple sclerosis (MS), thanks to a new nationwide research effort.  The national research project is the first of its kind in Australia and one of the first of its kind in the world.

"This collaborative research project has the potential to find crucial answers about a debilitating disease that affects millions of people worldwide," says the Hon. Mark Butler MP, Parliamentary Secretary for Health. More than 2.5 million people worldwide have MS, with the disease costing the Australian community alone an estimated $2 billion each year. Despite considerable research efforts so far, there are few effective treatments for MS.

The new research project will receive funding of $1 million over four years, starting this year, under the Australian Research Council’s Linkage Projects funding scheme and from MS Research Australia (MSRA), the research arm of MS Australia. The research is a major national collaboration between the University of Adelaide, Monash University, University of Queensland and the Sir Charles Gairdner Hospital, with the University of Adelaide as lead institution.

"With MS, there are a number of major stages that occur in the disease, including activation and remission," says the lead investigator, Professor Shaun McColl (School of Molecular & Biomedical Science, University of Adelaide).

"At each of these major stages, certain genes are activated. Those genes express proteins, and we believe these could have the effect of switching the disease on and off. If we can discover the key proteins and their roles in the development of MS, we could go a long way towards finding potential treatments or cures for the condition," he says.

The area of research involved in discovering such proteins is known as proteomics.

"There is no doubt that identification of a set of proteins that are specifically linked to different stages and pathological processes in MS will provide insight into the disease," says Professor Claude Bernard (Multiple Sclerosis Research Lab, Monash University). "It will also help evaluate the prognosis of patients with MS, guide their treatment and provide novel therapeutic approaches," he says.

Mr Jeremy Wright, Executive Director of MS Research Australia, says: "This is a natural step for MSRA to help researchers make important new discoveries that will translate into real outcomes for people with MS. Together with the ARC, we are investing $1 million into this promising new area for MS research."

Facts about MS
Multiple sclerosis is an autoimmune disease in which the body’s own immune cells attack a person’s central nervous system. MS affects the ability of nerve cells in the brain and spinal cord to communicate with each other. More than 2.5 million people around the world have MS. Three out of every four people diagnosed are women. MS is the most common neurological disease in young adults. It often strikes when a person is at their most active, usually in their early 20s, with increasing professional, social and/or family responsibilities.
Source:
Professor Shaun McColl
University of Adelaide

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MS Society Statement – Molecule Found In Brain May Protect From Damage Caused By MS
Main Category: Multiple Sclerosis
Article Date: 25 Aug 2009 – 0:00 PDT

The MS Society, the UK’s largest charity dedicated to supporting everyone affected by multiple sclerosis (MS), has responded to the news issued by the University of Bristol concerning the study of Galanin in MS.

The exact role of galanin in MS, and its potential as a treatment for MS, is still not certain but further research should clarify this. The researchers indicate that the next step will be to develop galanin into a drug that could be tested in clinical trials, but admit that this is some years off.

Dr Doug Brown, Research Manager at the MS Society, said: "This is an early study and there’s a long way to go before we understand what this means for people with MS, but any insight into how MS might be treated is valuable to researchers. This is worth further investigation."

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Hard To Treat Diseases (HTDS.PK) Scientists Present Encouraging Results For The Future Of Multiple Sclerosis Treatment
Main Category: Multiple Sclerosis
Article Date: 15 Aug 2009 – 1:00 PDT

Hard to Treat Diseases, Inc. (HTDS:PK), announced that there is great progress being made with the experimental findings to aid in the suppression or ultimately the cure of Multiple Sclerosis not only in their lab in Belgrade, but around the world.

In a recent study posted on Aug. 12, 2009 scientists have reversed the Multiple Sclerosis in mice. The study showed the suppression of the immune cells, forcing remission and reversing the disease in mice.

Multiple Sclerosis attacks the central nervous system. The researchers explained that "The new treatment, called GIFT15, is composed of two proteins, GSM-CSF and interleukin-15, that are fused in the lab. Normally, the individual proteins act to stimulate the immune system, but when they’re stuck together, the proteins suppress immune response, the researchers explained. They do this by converting B-cells — a type of white blood cell normally involved in immune response — into immune suppressive cells."

Dr. Jacques Galipeau and his collegues of the Jewish General Hospital Lady Davis Institute for Medical Research and McGill University in Montreal, took normal B-cells from mice and sprinkled GIFT-15 on the B-cells and when this was given in a single dose intravenously back to the mice that were ill with Multiple sclerosis not only did the disease go away but no significant side effects were seen in the mice as per the researchers.

Researchers in Belgrade are also making progress via using other methodologies that involve Ribavirin and Tiazofurin. Administration of ribavirin and tiazofurin attenuated proliferation of autoreactive T lymphocytes and their infiltration into the nervous tissue, and thereby prevented myelin destruction. These results are encouraging for the future of MS therapy.

In other company news, The company has received many inquiries from its shareholders and followers visa vie meeting the August 15th Q2 financials filings deadline. Mr. Terry Yuan CEO of HTDS said, "The management has decided to release HTDS consolidated financials today August 14th 2009 shortly after the market closes. The reason for that is twofold.

One, we are very pleased where our share price now sits as of close of business day August 13 2009.We have come a long way from being a sub,sub, penny stock, to a transparent well organized, well capitalized company; together with having the market finally begin to recognize our values, and the work our team is doing in Serbia and here in China. HTDS management’s aim is to continue with a good solid pace of adding value to HTDS and our shareholders. Secondly, HTDS management goal is to reward both our long and midterm shareholders, instead of catering to those seeking a daily quick profit. We remind our followers that the Q2 financial numbers, obviously will not reflect the recently announced contracts."

Safe Harbor Statement:

Information in this filing may contain statements about future expectations, plans, prospects or performance of Hard to Treat Diseases, Inc. that constitute forward-looking statements for purposes of the safe harbor Provision’s under the Private Securities Litigation Reform Act of 1995. The words or phrases "can be," "expects," "may affect," "believed," "estimate," "project," and similar words and phrases are intended to identify such forward-looking statements. HTDS Corporation cautions you that any forward-looking information provided by or on behalf of Hard to Treat Diseases, Inc. is not a guarantee of future performance. None of the information in this filing constitutes or is intended as an offer to sell securities or investment advice of any kind. Hard to Treat Diseases, Inc.’s actual results may differ materially from those anticipated in such forward-looking statements as a result of various important factors, some of which are beyond Hard to Treat Diseases, Inc.’s control. In addition to those discussed in Hard to Treat Diseases, Inc.’s press releases, public filings, and statements by Hard to Treat Diseases, Inc.’s management, including, but not limited to, Hard to Treat Diseases, Inc.’s estimate of the sufficiency of its existing capital resources, Hard to Treat Diseases, Inc.’s ability to raise additional capital to fund future operations, HTDS Corporation’s ability to repay its existing indebtedness, the uncertainties involved in estimating market opportunities and, in identifying contracts which match Hard to Treat Diseases, Inc.’s capability to be awarded contracts. All such forward-looking statements are current only as of the date on which such statements were made. Hard to Treat Diseases, Inc. does not undertake any obligation to publicly update any forward-looking statement to reflect events or circumstances after the date on which any such statement is made or to reflect the occurrence of unanticipated events.

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New Immune-Suppressing Treatment Forces Multiple Sclerosis Into Remission In Mice
Main Category: Multiple Sclerosis
Also Included In: Immune System / Vaccines
Article Date: 14 Aug 2009 – 0:00 PDT

 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.

Commenting on the study, Helen Yates, Multiple Sclerosis Resource Centre Chief Executive said, "This could be a very exciting development in the field of MS as well as a number of other conditions. As Dr. Galipeau rightly points out, this research needs much greater investigation and that requires funding. MSRC welcomes the findings of the Jewish General Hospital Lady Davis Institute for Medical Research and McGill University and hopes that further research is started soon."

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.

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Diabetes Drug Shows MS Potential
Main Category: Multiple Sclerosis
Also Included In: Diabetes;  Clinical Trials / Drug Trials;  Neurology / Neuroscience
Article Date: 29 Jul 2009 – 3:00 PDT

A small trial testing the benefits in multiple sclerosis (MS) of a drug used to treat type II diabetes, in combination with beta-interferon-1a, has been shown to potentially prevent brain cell loss.

The results of the trial in 21 people investigating the effects of pioglitazone (also known as Actos) were published last month in the Journal of Neuroimmunology.

Although the results of the trial showed some evidence of less damage in the brains of people with MS, there were too few people in the study to determine whether this effect was real.

Dr. Susan Kohlhaas, Research Communications Officer at the MS Society said, "These results suggest that pioglitazone may have some benefit in combination with beta-interferon for people with relapsing remitting MS, but this trial is not large enough to determine exactly what that benefit will be.

She added, "A larger clinical trial is needed to decide whether or not pioglitazone will be of benefit to people with MS."
View drug information on ACTOS

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FUT-175 Complements Experimental Autoimmune Encephalomyelitis (EAE)

Dr. Feng Lin and colleagues at Case Western Reserve University in Cleveland, OH have discovered that the complement inhibitor FUT-175 delays EAE onset. They present these findings in the August 2009 issue of The American Journal of Pathology.

Multiple sclerosis (MS) is an autoimmune disease in which the body’s immune response attacks the central nervous system (CNS), causing physical and cognitive disability. Complement, molecules involved in clearing infection, may enhance this misguided immune response.

Li et al therefore examined the effects of FUT-175, a drug with few clinical side effects that prevents the functions of complement, on the development of EAE, a mouse model of MS. They found that FUT-175 prevented production of activated complement and inhibited specific immune responses with little non-specific toxicity. FUT-175 treatment delayed EAE disease onset and decreased the severity of disease. Thus, FUT-175 may be a novel candidate to treat autoimmune diseases such as MS.

This study by Li et al "provide[s] further insight into how to most effectively apply … complement inhibitors for treating Tcell-mediated diseases."

Li Q, Nacion K, Bu H, Lin F: The complement inhibitor FUT-175 suppresses T cell autoreactivity in experimental autoimmune encephalomyelitis. Am J Pathol 2009, 175: 661-667

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Advances In Lab-Grown Motor Nerves Can Lead To Cures For Diabetic Neuropathy And Help Further Understand Multiple Sclerosis And Related ConditionsMain Category: Neurology / Neuroscience
Also Included In: Diabetes;  Multiple Sclerosis
Article Date: 23 Jul 2009 – 0:00 PDT

In the July issue of Biomaterials, published by Elsevier, researchers from the University of Central Florida (UCF) report on the first lab-grown motor nerves that are insulated and organized just like they are in the human body. The model system will drastically improve understanding of the causes of myelin-related conditions, such as diabetic neuropathy and later, possibly multiple sclerosis (MS). In addition, the model system will enable the discovery and testing of new drug therapies for these conditions.

MS, diabetic neuropathy, and many conditions that are caused by a loss of myelin, which forms protective insulation around our nerves, can be debilitating and even deadly. Adequate treatments do not yet exist. Researchers at the UCF have identified this to be a result of a deficiency in model research systems.

James Hickman, a bioengineer at UCF and the lead researcher on this project explained: "The nodes of Ranvier act like power station relays along the myelin sheath. They chemically boost signals, allowing them to get across breaks in myelin, or from node to node, at the electrically charged nodes of Ranvier. Nerve malfunctions, called neuropathies, involve a breakdown in the way the brain sends and receives electric signals along nerve cells, leading to malfunctions at the nodes of Ranvier, along with demyelination". Hickman’s team has now achieved the first successful model nodes of Ranvier formation on motor nerves in a defined serum-free culture system.

Researchers have long recognized the need for lab-grown motor nerve cells that myelinate and form nodes of Ranvier in order to use controlled lab conditions to zero in on the causes of demyelination. Yet, due to the complexity of the nervous system, it has been a challenge to study demyelinating neuropathies, and researchers have been confined to using animal models.

The main difference with this research was that Hickman’s group began with a model that was serum-free. They had already developed techniques for growing various nervous system cells in serum-free media, including motoneurons, and here they attempted myelination using the growth medium they have worked with for many years.

In the body, nerve cells grow in two distinct environments: In the peripheral nervous system (PNS), cells are exposed to blood and other fluids that contain high concentrations of protein, among various other constituents, depending on where the cells are located in the body. In the central nervous system (CNS), the spinal cord and brain are surrounded by cerebrospinal fluid that contains only trace amounts of protein. This system now allows for both the PNS and CNS to be studied in the same defined system.

The UCF team plans to use their new model system to explore the origins of diabetic neuropathy. Once the causes of myelin degradation are identified, targets for new drug therapies can be tested with the model. Other planned experiments will focus on how electrical signals travel through myelinated and unmyelinated nerves to reveal how nerves malfunction as well as for spinal cord injury studies. "Being able to study these fully developed structures means we can really start looking at these things in a way that just wasn’t possible before," commented Hickman.

Notes:
The full article is "Node of Ranvier formation on motoneurons in vitro" by John W. Rumsey, Mainak Das, Maria Stancescu, Marga

Bott, Cristina Fernandez-Valle, James J. Hickman. It appears in Biomaterials, Volume 30, Issue 21, July 2009, Pages

3567-3572, published by Elsevier.

Source:
Allyn Molina
Elsevier

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Gene Regulates Immune Cells’ Ability To Harm The Body
Main Category: Multiple Sclerosis
Also Included In: Genetics;  Arthritis / Rheumatology
Article Date: 17 Jul 2009 – 2:00 PDT

A recently identified gene allows immune cells to start the self-destructive processes thought to underlie autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis, researchers at Washington University School of Medicine in St. Louis have found.

Researchers showed that mice without the Batf gene lacked a type of inflammatory immune cell and were resistant to a procedure that normally induces an autoimmune condition similar to human MS. They plan to look for other genes and proteins influenced by Batf that could be targets for new treatments for autoimmune diseases.

"Batf allows immune cells to head down a pathway that’s been a very hot topic in immunology because of its potential links to autoimmune disease," says senior author Kenneth Murphy, M.D., Ph.D., professor of pathology and immunology and a Howard Hughes Medical Institute investigator. "We showed that Batf regulates the only other gene previously revealed to control this pathway, so Batf may have quite a bit to teach us about autoimmunity."

The findings appear in Nature on July 16.  Lead author Barbara Schraml, Ph.D., found that the loss of Batf affected immune cells known as T cells. Normally T cells take on specialized roles, becoming cells that promote various defensive responses or that recruit inflammatory cells to sites of infection. In mice without Batf, though, one of those roles was blocked: the mice had no inflammatory Th17 cells.

Researchers including Murphy first identified the Th17 pathway four years ago. While such cells help defend the body from bacterial infections, scientists have found that IL17, an inflammatory compound made by Th17 cells, is frequently present at sites of active autoimmune disease.

"Th17 cells draw in other immune cells to the site," Murphy says. "It makes the Th17 cell a bit like the instigator of an autoimmune riot lots of cells rush in, and harmful things can start to happen."

Batf is a transcription factor, which means that the protein made from the gene acts to turn the production of proteins from other genes on and off. Its only previously identified role was as a partner with another common transcription factor.

Schraml showed that Batf had to be present for Th17 cells to make ROR-gamma-T, the only other gene known to force T cells to become Th17 cells. She also found that the presence of Batf made it possible for T cells to make more IL17.

"Normally transcription factors do not make ideal drug targets, but our Batf-knockout mice provide a unique tool to find the other proteins that are important in the development of Th17 cells," says Murphy. "Those proteins could be good targets for treatments for autoimmune diseases."

Schraml BU, Hildner K, Ise W, Lee W-L, Smith WA-E, Solomon B, Sahota G, Sim J, Mukasa R, Cemerski S, Hatton RD, Stormo GD,

Weaver CT, Russell JH, Murphy TL, Murphy KM. The AP-1 transcription factor Batf controls TH17 differentiation. Nature, July 16, 2009.

Funding from the Howard Hughes Medical Institute, the National Institutes of Health and Daiichi-Sankyo Co. Ltd. supported this research.  Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through itsaffiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Source: Washington University in St. Louis

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Into How Brain Stem Cells Develop Into Cells Which Repair Damaged Tissue
Main Category: Multiple Sclerosis

Article Date: 03 Jul 2009 – 0:00 PDT

The joint research, funded by the National Multiple Sclerosis Society and the UK MS Society as well as the National Institutes of Health and Howard Hughes Medical Institute, was conducted by scientists at the University of California San Francisco (UCSF) and University of Cambridge and was published in the journal Genes and Development.

Multiple sclerosis is an autoimmune disease which is caused by the body’s immune system attacking nerve fibres and their protective insulation, the myelin sheath, in the central nervous system. This damage prevents the nerves from ‘firing’ properly, and then leads to their destruction, resulting in physical and intellectual disabilities.

It is currently thought that two components determine clinical outcomes in MS. First, it is important to stop ongoing damage (mainly achieved by controlling inflammation in the central nervous system). The second is to repair the damage that has occurred to the protective myelin sheaths surrounding the nerve fibres (this involves a regenerative process called remyelination in which new myelin sheaths are restored to nerve fibres).

While there exist several effective treatments to reduce inflammatory damage, no treatments are available to augment remyelination to repair the damage to nerve fibres. Critical to the development of such repair therapies is to understand how the brain’s own stem cells can replace the myelin forming cells (oligodendrocytes) lost in the disease. During early stages of the disease the brains own stem cells are surprisingly good at repairing damage in MS. However, for reasons that until now have not been well explained, they become less efficient as the disease progresses.

In this study the researchers have identified the Wnt pathway, which plays an active role in the maintenance and proliferation of stem cells, as a crucial determinant of whether oligodendrocytes can efficiently make myelin. Their studies demonstrate that if the Wnt pathway is abnormally active, then the process is inhibited. This opens up the exciting possibility that the repair can be enhanced in MS patients by drugs that block the Wnt pathway.

Professor Robin Franklin from the University of Cambridge, a co-senior author of the study, explained the significance of their findings: "The pathway we identified plays a critical role in whether repair to the damaged cells will or will not occur. Interestingly, mutations in this particular pathway are also involved in several cancers. In this regard, drugs that inhibit this pathway from signaling have been sought which might suppress tumour growth. These same drugs may also find a role in promoting repair in MS."

Lead author of the study, Stephen Fancy, PhD, a postdoctoral fellow in the lab of co-senior author David Rowitch, MD, PhD, a Howard Hughes Medical Institute Investigator at the University of California, San Francisco, said: "We believe we have made a significant step forward in understanding why repair might fail in neurological diseases such as MS by identifying a pathway which inhibits the myelin repair process," said the MS Society Director of Research, Jayne Spink, said: "We are delighted with the outcome of this outstanding research, which gives us greater knowledge of the mechanics of MS. This works opens up new avenues of research and lends itself to more study. Being able to uncover the secrets behind the damage caused in MS will take us forward in our understanding of this debilitating condition."

"Our studies work have implications for other diseases," said UCSF’s Rowitch. "In a condition called periventricular leukomalacia (PVL), which can lead to cerebral palsy in extremely premature infants, recent studies show a similar inability of oligodendrocytes to perform their important repair function. In respect to failed myelin repair, we see a parallel between the chronic demyelinated plaques of multiple sclerosis and the lesions of PVL."

Source:
Genevieve Maul
University of Cambridge