Missing link found between brain, immune system; major disease implications

In a stunning discovery that overturns decades of textbook teaching, researchers have determined that the brain is directly connected to the immune system by vessels previously thought not to exist. The discovery could have profound implications for diseases from autism to Alzheimer's to multiple sclerosis.

Maps of the lymphatic system: old (left) and updated to reflect UVA's discovery.

Credit: University of Virginia Health System

In a stunning discovery that overturns decades of textbook teaching, researchers at the University of Virginia School of Medicine have determined that the brain is directly connected to the immune system by vessels previously thought not to exist. That such vessels could have escaped detection when the lymphatic system has been so thoroughly mapped throughout the body is surprising on its own, but the true significance of the discovery lies in the effects it could have on the study and treatment of neurological diseases ranging from autism to Alzheimer's disease to multiple sclerosis.

"Instead of asking, 'How do we study the immune response of the brain?' 'Why do multiple sclerosis patients have the immune attacks?' now we can approach this mechanistically. Because the brain is like every other tissue connected to the peripheral immune system through meningeal lymphatic vessels," said Jonathan Kipnis, PhD, professor in the UVA Department of Neuroscience and director of UVA's Center for Brain Immunology and Glia (BIG). "It changes entirely the way we perceive the neuro-immune interaction. We always perceived it before as something esoteric that can't be studied. But now we can ask mechanistic questions."

"We believe that for every neurological disease that has an immune component to it, these vessels may play a major role," Kipnis said. "Hard to imagine that these vessels would not be involved in a [neurological] disease with an immune component."

New Discovery in Human Body

Kevin Lee, PhD, chairman of the UVA Department of Neuroscience, described his reaction to the discovery by Kipnis' lab: "The first time these guys showed me the basic result, I just said one sentence: 'They'll have to change the textbooks.' There has never been a lymphatic system for the central nervous system, and it was very clear from that first singular observation -- and they've done many studies since then to bolster the finding -- that it will fundamentally change the way people look at the central nervous system's relationship with the immune system."

Even Kipnis was skeptical initially. "I really did not believe there are structures in the body that we are not aware of. I thought the body was mapped," he said. "I thought that these discoveries ended somewhere around the middle of the last century. But apparently they have not."

'Very Well Hidden'

The discovery was made possible by the work of Antoine Louveau, PhD, a postdoctoral fellow in Kipnis' lab. The vessels were detected after Louveau developed a method to mount a mouse's meninges -- the membranes covering the brain -- on a single slide so that they could be examined as a whole. "It was fairly easy, actually," he said. "There was one trick: We fixed the meninges within the skullcap, so that the tissue is secured in its physiological condition, and then we dissected it. If we had done it the other way around, it wouldn't have worked."

After noticing vessel-like patterns in the distribution of immune cells on his slides, he tested for lymphatic vessels and there they were. The impossible existed. The soft-spoken Louveau recalled the moment: "I called Jony [Kipnis] to the microscope and I said, 'I think we have something.'"

As to how the brain's lymphatic vessels managed to escape notice all this time, Kipnis described them as "very well hidden" and noted that they follow a major blood vessel down into the sinuses, an area difficult to image. "It's so close to the blood vessel, you just miss it," he said. "If you don't know what you're after, you just miss it."

"Live imaging of these vessels was crucial to demonstrate their function, and it would not be possible without collaboration with Tajie Harris," Kipnis noted. Harris, a PhD, is an assistant professor of neuroscience and a member of the BIG center. Kipnis also saluted the "phenomenal" surgical skills of Igor Smirnov, a research associate in the Kipnis lab whose work was critical to the imaging success of the study.

Alzheimer's, Autism, MS and Beyond

The unexpected presence of the lymphatic vessels raises a tremendous number of questions that now need answers, both about the workings of the brain and the diseases that plague it. For example, take Alzheimer's disease. "In Alzheimer's, there are accumulations of big protein chunks in the brain," Kipnis said. "We think they may be accumulating in the brain because they're not being efficiently removed by these vessels." He noted that the vessels look different with age, so the role they play in aging is another avenue to explore. And there's an enormous array of other neurological diseases, from autism to multiple sclerosis, that must be reconsidered in light of the presence of something science insisted did not exist.

---

Story Source:

The above post is reprinted from materials provided by University of Virginia Health System. Note: Materials may be edited for content and length.

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Journal Reference:

1. Antoine Louveau, Igor Smirnov, Timothy J. Keyes, Jacob D. Eccles, Sherin J. Rouhani, J. David Peske, Noel C. Derecki, David Castle, James W. Mandell, Kevin S. Lee, Tajie H. Harris, Jonathan Kipnis. Structural and functional features of central nervous system lymphatic vessels. Nature, 2015; DOI: 10.1038/nature14432

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Missing link found between brain, immune system; major disease implications

In a stunning discovery that overturns decades of textbook teaching, researchers have determined that the brain is directly connected to the immune system by vessels previously thought not to exist. The discovery could have profound implications for diseases from autism to Alzheimer's to multiple sclerosis.

Maps of the lymphatic system: old (left) and updated to reflect UVA's discovery.

Credit: University of Virginia Health System

In a stunning discovery that overturns decades of textbook teaching, researchers at the University of Virginia School of Medicine have determined that the brain is directly connected to the immune system by vessels previously thought not to exist. That such vessels could have escaped detection when the lymphatic system has been so thoroughly mapped throughout the body is surprising on its own, but the true significance of the discovery lies in the effects it could have on the study and treatment of neurological diseases ranging from autism to Alzheimer's disease to multiple sclerosis.

"Instead of asking, 'How do we study the immune response of the brain?' 'Why do multiple sclerosis patients have the immune attacks?' now we can approach this mechanistically. Because the brain is like every other tissue connected to the peripheral immune system through meningeal lymphatic vessels," said Jonathan Kipnis, PhD, professor in the UVA Department of Neuroscience and director of UVA's Center for Brain Immunology and Glia (BIG). "It changes entirely the way we perceive the neuro-immune interaction. We always perceived it before as something esoteric that can't be studied. But now we can ask mechanistic questions."

"We believe that for every neurological disease that has an immune component to it, these vessels may play a major role," Kipnis said. "Hard to imagine that these vessels would not be involved in a [neurological] disease with an immune component."

New Discovery in Human Body

Kevin Lee, PhD, chairman of the UVA Department of Neuroscience, described his reaction to the discovery by Kipnis' lab: "The first time these guys showed me the basic result, I just said one sentence: 'They'll have to change the textbooks.' There has never been a lymphatic system for the central nervous system, and it was very clear from that first singular observation -- and they've done many studies since then to bolster the finding -- that it will fundamentally change the way people look at the central nervous system's relationship with the immune system."

Even Kipnis was skeptical initially. "I really did not believe there are structures in the body that we are not aware of. I thought the body was mapped," he said. "I thought that these discoveries ended somewhere around the middle of the last century. But apparently they have not."

'Very Well Hidden'

The discovery was made possible by the work of Antoine Louveau, PhD, a postdoctoral fellow in Kipnis' lab. The vessels were detected after Louveau developed a method to mount a mouse's meninges -- the membranes covering the brain -- on a single slide so that they could be examined as a whole. "It was fairly easy, actually," he said. "There was one trick: We fixed the meninges within the skullcap, so that the tissue is secured in its physiological condition, and then we dissected it. If we had done it the other way around, it wouldn't have worked."

After noticing vessel-like patterns in the distribution of immune cells on his slides, he tested for lymphatic vessels and there they were. The impossible existed. The soft-spoken Louveau recalled the moment: "I called Jony [Kipnis] to the microscope and I said, 'I think we have something.'"

As to how the brain's lymphatic vessels managed to escape notice all this time, Kipnis described them as "very well hidden" and noted that they follow a major blood vessel down into the sinuses, an area difficult to image. "It's so close to the blood vessel, you just miss it," he said. "If you don't know what you're after, you just miss it."

"Live imaging of these vessels was crucial to demonstrate their function, and it would not be possible without collaboration with Tajie Harris," Kipnis noted. Harris, a PhD, is an assistant professor of neuroscience and a member of the BIG center. Kipnis also saluted the "phenomenal" surgical skills of Igor Smirnov, a research associate in the Kipnis lab whose work was critical to the imaging success of the study.

Alzheimer's, Autism, MS and Beyond

The unexpected presence of the lymphatic vessels raises a tremendous number of questions that now need answers, both about the workings of the brain and the diseases that plague it. For example, take Alzheimer's disease. "In Alzheimer's, there are accumulations of big protein chunks in the brain," Kipnis said. "We think they may be accumulating in the brain because they're not being efficiently removed by these vessels." He noted that the vessels look different with age, so the role they play in aging is another avenue to explore. And there's an enormous array of other neurological diseases, from autism to multiple sclerosis, that must be reconsidered in light of the presence of something science insisted did not exist.

---

Story Source:

The above story is based on materials provided by University of Virginia Health System. Note: Materials may be edited for content and length.

Continue to Read more ...

Multiple sclerosis: becoming aware of its invisible difficulties

Multiple sclerosis affects an estimated 2.3 million people worldwide, although chances are if you were to pass somebody with the condition in the street you might not realize they had the condition at all. In fact, they might not realize it themselves. Multiple sclerosis can be as mysterious as it is complex and debilitating.

Defining and diagnosing multiple sclerosis is a notoriously difficult task due to the lack of a single test for the condition.

At present, nobody knows precisely what causes this disease of the central nervous system. Its severity ranges dramatically from relatively benign cases to the devastatingly disabling, bringing partial or complete paralysis to the body.

According to the National Institutes of Health (NIH), somewhere between 250,000 and 350,000 people in the US have been diagnosed with multiple sclerosis (MS). Because the Centers for Disease Control and Prevention (CDC) do not require physicians to report new diagnoses of the disease, the prevalence of MS can only be estimated.

In addition, many symptoms of the condition are invisible. MS is a notoriously difficult disease to diagnose, and so many people must live with their chronic disease untreated until doctors can rule out all other possibilities.

This week is National MS Awareness Week in the US. For this Spotlight feature, we will be taking a look at this complex and elusive condition in an attempt to pin down precisely what makes it such a mysterious and difficult disease to contend with.

What is MS?

MS is a whereby the body's immune system targets its own central nervous system - the brain, spinal cord and optic nerves. At present, the precise target that the immune system attacks - the antigen - is unknown, leading experts to regard MS as "immune-mediated" rather than an "autoimmune" disease.

When MS attacks the central nervous system, a fatty substance that protects the nerve fibers called myelin is damaged, along with the nerve fibers themselves. After becoming damaged, myelin forms scar tissue, in a process known as sclerosis.

The damage to the myelin and nerve fibers leads to the disruption and interruption of electrical signals being transmitted throughout the central nervous system, and it is this effect that MS has on the nerve impulses that produces the symptoms of the disease.

People with MS can experience a wide range of symptoms. The National MS Society (NMSS) emphasize the point that no two people have exactly the same MS symptoms, and each person's symptoms can change or fluctuate over time.

Due to the role the central nervous system has in the body, many areas can be affected by the disease. Common symptoms include fatigue, walking difficulties, vision problems, bladder problems, pain and cognitive changes.

One thing that many of these symptoms have in common is that they can be described as "invisible symptoms." In the video below, Rosalind Kalb, PhD, from the NMSS, discusses the effect of these symptoms and some of the challenges they present:

Due to the presence of invisible symptoms, some people with MS may appear to be much healthier than they are. Others might not be aware of symptoms they are inwardly struggling with, and, therefore, might have unreasonable expectations of the person with MS.

Another element of the disease that alters people's expectations is that MS has several different disease courses that have been identified - ways in which the disease presents itself and develops over time. The NMSS describe the following:

• Relapsing-remitting (RRMS) - around 85% of people with MS are believed to have this form, characterized by clearly defined flare-ups (relapses) of worsening symptoms, followed by periods of partial or complete recovery (remissions). During remission periods, no disease progression is apparent
• Secondary-progressive (SPMS) - many people transition to this form of the disease, whereby MS begins to progress more steadily, with or without periods of remission
• Primary-progressive (PPMS) - around 10% of people are believed to have this form of MS, characterized by neurologic function steadily worsening over time. While there may be temporary improvements from time to time, there are no distinct relapses or remissions
• Progressive-relapsing (PRMS) - the least common disease course, whereby MS is characterized by steadily worsening neurologic function with occasional relapses occurring from time to time. In PRMS, the disease continues to progress without remissions.

A clear line of communication between individuals and their physicians is vital. Symptoms such as fatigue can also occur as a result of other conditions, such as interrupted sleep due to sleep apnea. People with MS must be wary when a new symptom presents; it is important to discuss symptoms with a health care professional rather than simply attributing it to MS.

The prospect of an MS diagnosis can be a daunting one, and not just because of the symptoms that can potentially be experienced. At present, there is no known cure for MS, although studies often claim to offer hope.

Rewiring the immune system?

In the UK, The Telegraph reported that a "'miracle' stem cell therapy reverses multiple sclerosis." For the study, published inJAMA, doctors used chemotherapy to "knock out" parts of the immune system that were not working properly and then rebuild them using stem cells from the patient's blood.

Could stem cells be used to "reboot" the immune system of people with MS?

The article reporting on the study describes wheelchair-bound patients able to walk again and blind patients having their vision restored. These are dream results for many MS patients. However, the British National Health Service (NHS) were swift to put the story in perspective.

Although improvements were made in the levels of disability experienced by almost 64% of the study participants, the study was limited by only focusing on one form of MS - RRMS - and by not including a control group in the investigation. As a result, the researchers cannot be certain that these improvements are attributable to the treatment.

"These preliminary findings from this uncontrolled study require randomized trials," the authors of the study write, in acknowledgment of the study's limitations.

"It's also worth noting that not everyone will be able to tolerate the aggressive chemotherapy used," add the NHS on their Choices website, "and that the technique did not work for people with more severe or longstanding MS (over 10 years)."

This example serves to illustrate that there is still a great deal of work that needs to be carried out before patients can look forward to definitive treatment for this chronic illness. The presence of different courses of MS also means that levels of treatment available vary depending on what form of MS a person has.

Dr. Annette Langer-Gould, a research scientist and neurologist at Kaiser Permanente in Pasadena, CA, described to Medical News Today the current situation regarding MS treatment in the US:

"We have highly effective immunomodulatory treatments for relapsing, nonprogressive MS, somewhat effective treatments for relapsing progressive MS, but, unfortunately, progressive, nonrelapsing MS is a neurodegenerative process more similar to Alzheimer's disease and Parkinson's disease than to relapsing forms of MS."

For patients with progressive MS that does not relapse, the focus is a proactive management of symptoms to maximize function and quality of life. "This takes more time and energy on the part of the physician and patient, and a multidisciplinary approach often with the help of a social worker, primary care physician, physical and occupational therapy and urology," she explained.

Further complexity

Dr. Langer-Gould also drew MNT's attention to the categorization of the disease courses of MS. In contrast to the four defined courses described by the NMSS, Dr. Langer-Gould said that newer terms were being used:

"The subtypes of MS are relapsing, nonprogressive MS, relapsing progressive MS and progressive, nonrelapsing MS. The older terms - primary or secondary progressive MS, chronic progressive MS - are terms that are no longer being used because they confuse general neurologists and patients and don't really help guide care."

While experts have previously accepted that MS is more prevalent among white people than black people, a recent study has refuted this claim.

MS is a disease that appears to be constantly redefined the more that researchers and experts find out about it. The way in which the disease is dealt with has changed greatly in a short period, and as more is discovered, we can expect the way MS is treated and discussed to continue changing.

A study from Kaiser Permanente examining the electronic health records of over 3.5 million members in Southern California suggested that MS is more common in black women than in white women. These findings directly contrast with what had previously been established: that black people were less susceptible to the disease.

Conflicting findings arising from studies such as this demonstrate the level of mystery that surrounds MS. Experts believe that the development of MS is influenced by environmental factors, exposure to infectious microbes and genetic factors, but as yet they have not been able to pin the disease down precisely.

Such uncertainty is also present in the diagnosis of MS. As symptoms of the disease can vary so greatly, it can take a considerable amount of time before a patient is successfully diagnosed.

"Recognizing patients who are at high risk of early disability (or imminent risk of disability) and getting these individuals on the optimal treatment plan is the biggest challenge general neurologists face today," suggested Dr. Langer-Gould.

As new forms of treatment for the management of MS symptoms have been discovered, the need for quick diagnosis has changed. When there was no effective treatment for highly aggressive MS, being able to identify people with this form of the disease was less critical.

"Now we are lucky that we do have such highly effective medications (natalizumab and fingolimod and in some instances rituximab as well), but timely identification of the individuals who need these treatments remains a critical barrier," Dr. Langer-Gould explained.

Invisible symptoms, invisible disease?

Unfortunately, such treatments do not come cheap in the US. "The other big challenge for many Americans with MS is the astronomical rise in prices of the MS medications, including treatments that are not particularly effective," Dr. Langer-Gould told us. "For many people their co-pay is far more than they can afford."

She suggests that action needs to be taken, with patient advocacy groups working alongside Congress in order to help bring affordable medications to the market while simultaneously controlling the rising costs of medication.

Another aspect of MS that the government could help with is tracking the disease on an epidemiological level. As mentioned earlier in this article, physicians are not required to report to a central database whenever a new diagnosis is made.

A lack of reporting in combination with difficulties in diagnosis and classifying cases of MS - there is no standard method for testing or identifying the disease - means that all epidemiological numbers are estimated and contributes to the lack of certainty surrounding the disease.

Keeping a centralized record of the number of MS cases in some way would certainly help scientists attempting to track the incidence and prevalence of the disease, and could contribute toward helping determine what causes MS.

MS is one of the most complex diseases that an individual can experience. Due to this fact, it is important that awareness of the condition is raised. For more information, take a look at the NMSS information on what can be done to raise awareness or the MNT Knowledge Center page about the condition.

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Hope that nerve damage in MS could be repaired

By shedding light on how cells regenerate the myelin sheath surrounding nerve fibres in the brain, a new study published in Nature Neuroscience opens the door to treatments that could repair nerve damage and restore lost function in patients with multiple sclerosis (MS).
MS is a disease in which the immune system attacks and destroys myelin, the protein that insulates the nerves in the spinal cord, brain and optic nerve and stops the electrical signals from leaking out.
As the myelin is gradually destroyed, patients experience symptoms ranging from mild numbness in the limbs to paralysis or blindness.
The disease progresses not just because the immune system gradually destroys the myelin, but also because a natural repair process fails. Cells called oligodendrocytes are able to repair the myelin damage themselves - "remyelination" - but in MS this fails after a while.
There are over 400,000 living with MS in the European Union. There are currently no approved therapies that tackle the disease by promoting regeneration of the myelin.

Two immune cell findings may be important for future therapy

In this latest study, led by the Universities of Edinburgh and Cambridge in the UK, researchers describe how they studied immune cells called macrophages, known to be involved in remyelination, and found two important features that could lead to new therapies that promote myelin regeneration:

1. For remyelination to proceed, macrophages have to become anti-inflammatory
2. Macrophages release a protein called activin-A that actively encourages remyelination.

First author Dr Veronique Miron, of the Medical Council Centre for Regenerative Medicine at the University of Edinburgh, says in a statement:

"Approved therapies for multiple sclerosis work by reducing the initial myelin injury - they do not promote myelin regeneration.
This study could help find new drug targets to enhance myelin regeneration and help to restore lost function in patients with multiple sclerosis."

For their study, Miron and colleagues examined myelin regeneration in human tissue samples and in mice.
They wanted to understand what stimulates remyelination and which biological molecules, cells, or other factors may be involved that could serve as targets for regenerative treatments that restore lost vision, movement and other functions in people with MS.
Previous studies have shown that macrophages - immune cells that gobble up disease pathogens, debris and other undesirable materials, among other things - are also involved in regeneration.
For example, there is a group of macrophages called M2 that is essential for regenerating skin and muscle.

Hunt for potential drug targets

So what Miron and the team wanted to find out was whether M2 macrophages were also involved in myelin regeneration, and if so, were there particular molecules involved in stimulating remyelination that could serve as useful drug targets?
On examining a mouse model of human myelin damage and regeneration, the team found that M2 macrophages were present and increased in number when remyelination started. This suggests, they say, that M2 macrophages may control remyelination.
Previous research had already established that oligodendrocytes are the cells that normally produce the myelin found in the brain and spinal cord, so Miron and colleagues set about trying to discover if M2 macrophages were able to trigger the oligodendrocytes on their own, or whether they needed to work with another group of cells or processes.
To find out they put some oligodendrocytes in a test tube and exposed them to proteins released by M2 macrophages.
The result was a success. Exposure to M2 macrophage proteins spurred the oligodendrocytes to make more myelin.
The researchers also found that when they took M2 macrophages out of the equation, remyelination dramatically reduced, showing they were necessary for myelin to regenerate.
This was confirmed in further examinations of mouse models of remyelination, and brain tissue from people with MS. The researchers found in both cases that high numbers of M2 macrophages are present when remyelination is efficient, and the numbers are vastly reduced when it is not.
The team also found that a protein produced by macrophages, activin-A, contributes to the regenerative effects of M2 macrophages.
They found high levels of activin-A in M2 macrophages when remyelination was starting and also when they added the protein to oligodendrocytes in test tubes they started to make myelin.
To confirm the role of activin-A, the researchers blocked its effect on oligodendrocytes after myelin damage, and discovered the M2 macrophages were not as able to stimulate them to make more myelin.
They conclude that their findings point to a key step in myelin regenration, namely that when M2 macrophages release activin-A, they spur oligodendrocytes to make myelin.

Potential for synergistic drugs

The study suggests it may be possible to partner drugs that reduce the initial myelin damage, with ones that regenerate it in the central nervous system and thus restore lost functions in MS patients.
The researchers now plan to look in more detail at how activin-A works and whether its effects can be enhanced.
The study was funded by the MS Society, the Wellcome Trust and the Multiple Sclerosis Society of Canada.
In another study published earlier this year, researchers described how a new treatment for MS that resets the patient's immune system was found to be safe and well tolerated in a small trial.

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State Battles Federal Government for Independence in Medical Marijuana Case

Magistrate Maria-Elena James ruled that a cannabis dispensary in Oakland, CA, is free to stay open while local authorities fight federal prosecution to shut it down, reports Reuters.
The ruling came in on July 3rd, just under the wire for local supporters of the Harborside Health Center to celebrate their temporary medical marijuana freedom on the Fourth of July.
This long-standing court case between California and the US government is currently in an appeals stage, whereby the local government is contesting Magistrate James's February decision that the city has no right to interfere in a federal prosecutor's action to shut down or seize the property of the Oakland-based pot store.
Currently in the US, marijuana is not an approved drug according to the Federal Drug Administration (FDA), but rather an illegal narcotic. Still, the District of Columbia and 16 states have deemed cannabis to be legal if sold as a medicine prescribed by a doctor.

The medical world weighs in on marijuana

Outside of politics, the medical community has waged its own debate over the last decade about the health merits of marijuana. The Center for Medicinal Cannabis Research (CMCR), which is run by the University of California, has been conducting scientific studies for several years.
In one study involving effects of cannabis on pain from HIV-related peripheral neuropathy, the CMCR concluded that 52% of patients who smoked marijuana had over a 30% reduction in pain, compared to 24% in the placebo group.
And in another study conducted by the CMCR and published by the Canadian Medical Association Journal (CMAJ), researchers found that smoked cannabis significantly reduced symptoms and pain associated with multiple sclerosis spasticity.

Cannabis for medical use is a polarizing issue

Still, the medical community is divided, with some professionals calling for more in-depth studies and research before medical marijuana is prescribed to patients.
A paper published by the National Center for Biotechnology Information (NCBI) suggests that:

"over the longer term cannabis may have unwanted systemic and psychoactive adverse effects that must be taken into consideration in chronic pain populations, who have high rates of co-occurring medical illness and co-morbid psychiatric and substance use disorders."

Whether a medical or political issue, medical marijuana has strong supporters who are either for or against it.
In an act of solidarity with the state's physicians, the Medical Board of California published standards for physicians who prescribe medical marijuana to patients.
According to a statement from the Board, physicians who prescribe cannabis will not receive any ill effects toward their physician's license, so long as they follow good medical practice during patient consultation, including:

• History and good faith examination of the patient
• Development of a treatment plan with objectives
• Provision of informed consent including discussion of side effects
• Periodic review of the treatment's efficacy
• Consultation, as necessary
• Proper record keeping that supports the decision to recommend the use of medical marijuana.

Though the case involving the fate of Oakland's medical marijuana dispensary has yet to be resolved, Cedric Chao, the attorney representing the city in the case, remains positive, saying:

"The court has recognized that Oakland has legitimate interests in protecting its residents' health, in promoting public safety, and in protecting the integrity of its legislative framework for the regulation of medical cannabis. Today's order, coming right before the July Fourth holiday, reminds us all that one of the strengths of our country is its independent judiciary."

The state of California and supporters of the Harborside Health Center may be on the verge of a metaphorical Boston Tea Party scenario with the federal government, but for this Independence Day, they can hold onto their tea.
Or even smoke it.

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Salt May Play Role In Autoimmune Disease

A healthy immune system is a finely balanced system: too little activity and we fall prey to disease, too much, and it attacks our own tissue, triggering autoimmune diseases like multiple sclerosis. Now three studies published online this week in Nature suggest the amount of salt we eat may influence this balance by indirectly encouraging the overproduction of immune cells.

In the three studies the researchers focused on a group of immune cells known as T cells because they play an important role in clearing disease-causing pathogens and also in autoimmune disease. They were particularly interested in how T cells develop.

TH17 Cells Have Been Implicated In a Number of Autoimmune Diseases

Previous research has suggested that some types of autoimmunity may be tied to overproduction of a type of immune cell called TH17, a type of helper T cell that protects against pathogens.

However, Th17 cells have also been implicated in diseases like multiple sclerosis, psoriasis, rheumatoid arthritis, and ankylosing spondylitis. Treatments for some of these diseases, such as psoriasis, involve manipulating T cell function.

Until now, scientists have struggled to pinpoint the molecular machinery behind the overproduction of TH17 cells, partly because the usual way of activating native immune cells in the lab, such as RNA interference (RNAi) to manipulate genes, either harms them or disturbs their development.

First Study: Using Nanowires to Manipulate Genes in TH17 Cells

But, by using a new method based on nanowires to manipulate genes in immune cells without altering the cells' functions, the authors of the first study, led by Aviv Regev, a biologist at the Massachusetts Institute of Technology, in Cambridge, in the US, were able "systematically" to assemble and validate a model of how TH17 cells are controlled in mice.

Regev got the idea for the new approach after attending a lecture given by co-author, Hongkun Park, a physicist at Harvard University, also in Cambridge, on how to use silicone nanowires to disarm single genes in cells without disturbing the way the cells operate.

She says in a report by Nature NEWS that without such a model they would probably have been only "guessing in the dark".

Co-author Vijay Kuchroo, an immunologist at Brigham and Women's Hospital in Boston, Massachusetts, says in a statement that until they got the new technology using the nanowires, every time they downregulated a gene (with the previous technology), the cell would change.

The team identified and validated 39 "regulatory factors" altogether, uncovering the most important points in the network and untangling their biological meaning.

They conclude that their findings highlight "novel drug targets for controlling TH17 cell differentiation".

Second Study: Discovering Key Role of SGK1 Signal

In the second study, Regev and another team, this time led by Kuchroo, took snapshots of how immune cells were produced over a three day period.

One protein in particular grabbed their attention, SGK1 (short for serum glucocorticoid kinase 1), a well-studied signaling protein that had not been described in T cells before, but is known to regulate how salt is absorbed in cells of the gut and in kidneys.

By manipulating salt levels in cultured mouse cells, the researchers found SGK1 expression was stronger the more salt there was, causing more TH17 cells to be produced.

Kuchroo says:

"If you incrementally increase salt, you get generation after generation of these TH17 cells."

Third Study: Confirming Findings in Mouse and Human Cells

In the third study, researchers led by David Hafler, a neurologist at Yale University in New Haven, Connecticut, confirmed the findings in mouse and human cells.

Hafler says this was easy to do, "you just add salt".

They also found that mice fed with a high-salt diet developed a more severe form of experimental autoimmune encephalomyelitis (EAE), "in line with augmented central nervous system infiltrating and peripherally induced antigen-specific TH17 cells".

EAE is an animal model of brain inflammation that is used to study autoimmune disease in the lab.

Hafler and colleagues conclude that " ... increased dietary salt intake might represent an environmental risk factor for the development of autoimmune diseases through the induction of pathogenic TH17 cells".

Implications

The researchers do not wish people to go away from these findings assuming that high salt diets alone cause autoimmune diseases.

In their studies they had to induce autoimmune disease, the salt played an additional role. And there are other factors too, as Kuchroo explains:

"It's not just salt, of course. We have this genetic architecture - genes that have been linked to various forms of autoimmune diseases, and predispose a person to developing autoimmune diseases. But we also suspect that environmental factors - infection, smoking, and lack of sunlight and Vitamin D - may play a role."

"Salt could be one more thing on the list of predisposing environmental factors that may promote the development of autoimmunity," says Kuchroo.

Regev also says it is far too early to say people shouldn't eat salt because it leads to autoimmune disease.

"We're putting forth an interesting hypothesis - a connection between salt and autoimmunity - that now must be tested through careful epidemiological studies in humans," she explains.

Hafler adds, "As a physician, I'm very cautious."

He says people should be on a low-salt diet anyway, for general health reasons.

The researchers now plan to apply the new model and build on the results to identify and follow up on potential drug targets.

Support for the research came from the National Human Genome Research Institute, the National Institutes of Health, National Multiple Sclerosis Society, the Klarman Cell Observatory, Guthy Jackson Foundation, and the Austrian Science Fund.

A study published in 2012 finds that the the prevalence and incidence of autoimmune diseases is on the rise in the US and researchers at the Center for Disease Control and Prevention are unsure why.

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What Is MS? What Is Multiple Sclerosis?

Multiple sclerosis, also known as MS, is a chronic disease that attacks the central nervous system, i.e. the brain, spinal cord and optic nerves. In severe cases the patient becomes paralyzed and/or blind, while in milder cases there may be numbness in the limbs.

Over 350,000 people have MS in the USA. The Cleveland Clinic says that MS-related health care costs are thought to be over $10 billion per year in the United States.

According to the National Health Service, UK, approximately 100,000 people live with multiple sclerosis in Great Britain. Symptoms usually appear initially between 15 and 45 years of age. Women are twice as likely to get MS than men.

The term Multiple Sclerosis comes from the Latin multus plus plica meaning "fold", and the Greek sklerosis meaning "hardening".

According to MediLexicon's medical dictionary, Multiple Sclerosis (MS) is:

"a common demyelinating disorder of the central nervous system, causing patches of sclerosis (plaques) in the brain and spinal cord; occurs primarily in young adults, and has protean clinical manifestations, depending on the location and size of the plaque; typical symptoms include visual loss, diplopia, nystagmus, dysarthria, weakness, paresthesias, bladder abnormalities, and mood alterations; characteristically, the plaques are "separated in time and space" and clinically the symptoms show exacerbations and remissions".

With MS the central nervous system (CNS) is attacked by the person's own immune system. That is why MS is known as an auto-immune disease.

Nerve fibers are surrounded by myelin, which protects them. Myelin also helps conduct electrical signals (impulses) - i.e. myelin facilitates a good flow of electricity along the nervous system from the brain. Myelin regulates a key protein involved in sending long-distant signals.

The myelin of a patient with MS disappears in multiple areas. This leaves a scar (sclerosis). Multiple Sclerosis means "Scar Tissue in Multiple Areas". The areas where there is either not enough or no myelin are called plaques or lesions. As the lesions get worse the nerve fiber can break or become damaged.

When a nerve fiber has less myelin the electrical impulses received from the brain do not flow smoothly to the target nerve - when there is no myelin the nerve fibers cannot conduct the electrical impulses at all. The electrical impulses are instructions from the brain to carry out actions, such as to move a muscle. With MS, you cannot get your body to do what your brain wants it to do.

Who Can Develop Multiple Sclerosis?

• MS can affect people of all ages.


• It is more common among people aged from 20 to 50 years.


• More women develop MS than men.


• People of European descent are more likely to develop MS, compared to other people. However, people of all ancestries can get it.


• You can inherit a greater susceptibility of getting MS from your parents.


• In 2007 the World Health Organization (WHO) estimated that approximately 2.5 million people had MS.


• Multiple sclerosis rates are higher the further away you live from the equator. This leads many to believe that exposure to sunlight impacts on MS risk.

What Are The Causes Of MS?

Although experts are still uncertain, most of them say that the person's own immune system attacks the myelin as if it were an undesirable foreign body - in the same way our immune system might attack a virus or bacteria.

Why might our immune system attack the myelin?

The reasons could be:

• Genetic - some studies have shown that the genes we inherit from our parents may, in part, impact on our risk of developing MS. If you have a parent, sibling, or grandparent who has/had MS, your risk of developing it yourself is greater than average.
  
  Several genes are most likely involved in influencing multiple sclerosis risk, experts say. Scientists believe that a set of gene variants we are born with, plus exposure to some environmental trigger(s), affect the immune system of some people which eventually leads to MS symptoms.
  
  We are probably not that far from identifying those gene variants. The largest MS genetic study ever undertaken, involving 250 scientists from around the world and led by the Universities of Cambridge and Oxford, reported in the journal Nature in August 2011 that over 50 genes had been identified and associated with MS.


• Environmental - MS prevalence varies according to geographical area and population groups. MS is much more common in northern Europe than southern Europe, northern USA than southern USA. It seems that the more exposure to sunlight we have, the lower our MS risk is. The more sunlight we are exposed to, the less likely we are to have low levels of vitamin D - therefore, long-term vitamin D levels probably play a role in MS risk.
  
  Italian scientists explained in July 2012 at the 22nd Meeting of the European Neurological Society (ENS) in Prague, Czech Republic, that people with high vitamin D levels are less likely to develop MS.
  
  In the USA, Caucasian people have a higher risk of developing MS than other racial groups; regardless of geographical location.
  
  Studies indicate that people who move from a higher-risk area to a lower-risk one only acquire the risk of the new area if they move before they reach adolescence. This means that there is something in the environment we are exposed to early in life which influences risk.
  
  Exposure to a toxic substance, such as a heavy metal or solvent has been suggested, but no clear conclusions have been reached.
  
  People with MS are less likely to suffer from gout. MS patients have lower-than-average levels of uric acid in their system, which leads scientists to believe that uric acid protects from MS.
  
  It is unlikely there is just one trigger, experts say, but rather MS is probably triggered by multiple factors.


• Infections - doctors and researchers have often mentioned viruses, such as Epstein-Barr (mononucleosis), varicella zoster, as possible MS triggers; however, this theory has not been backed up scientifically.


• Too much salt - too much salt may trigger the immune system, causing autoimmune diseases, researchers from the Massachusetts Institute of Technology reported in the journal Nature (March 2013 issue). The excessive consumption of salt might increase our risk of developing multiple sclerosis.

What Are The Signs And Symptoms Of MS?

MS affects the central nervous system, which controls all the actions in the body. When nerve fibers which carry messges to and from the brain are damaged, symptoms may occur in any part of the body.

In most cases, signs and symptoms generally appear between the ages of 20 and 40. For some patients, they are so mild that they do not notice anything until much later in the course of the disease. Others may be aware of them very early on

The most common symptoms are:

• Bladder problems - patients may have difficulty emptying their bladder completely, needing to go to the toilet more frequently. Urge incontinence (suddenly dying to go, or unintentional passing of urine), and Nocturia (needing to go frequently during the night) are also common symptoms.


• Bowel problems - half of all MS patients are frequently affected with constipation, which can sometimes be serious (fecal impaction). If the fecal impaction is not resolved, the problem may lead to bowel incontinence.


• Cognitive Function - according to the Multiple Sclerosis Resource Center, UK, about 50% of people with MS say they experience cognitive problems to some extent, increasing to 80% among the most severe cases. The most commonly reported cognitive abnormalities include problems with memory, abstraction, attention and word finding.
  
  In March 2012, researchers from the Kessler foundation reported on a study they carried out which showed that warmer weather has a negative effect on the cognitive performance of patients with MS.


• Depression - researchers from UCLA say MS patients have a 50% chance of developing depression. They add that depression among MS patients is not psychological, but linked to atrophy in part of the hippocampus.


• Emotional Changes - MS may have a profound emotional effect on the individual when a diagnosis is first made. It may be hard to adjust to the diagnosis of such an unpredictable disorder, which carries a risk of some level of physical disability. Also, demyelination and nerve fiber damage in the brain can cause emotional changes. In short, a person with MS may experience emotional changes for either psychological or physical reasons, or both.
  
  Researchers from the LSU Health Sciences Center New Orleans, USA, showed that stress management treatment reduced the formation of new brain lesions in people with MS considerably.


• Fatigue - this is one of the most common symptoms of MS, and affects approximately 80% of patients. The person's ability to function properly at work and at home may be seriously undermined by fatigue. It is the main reason MS patients leave their jobs.


• Dizziness and Vertigo - people with MS commonly experience dizziness and problems with balance. Vertigo is not the same as dizziness; it is a sensation that the room around you is moving or spinning.


• Head movements may cause electric-shock like sensations.


• Numbness or weakness - usually in one or more limbs, and typically affects just one side of the body at a time, or just the bottom half of the body.


• Pain or tingling in some parts of the body.


• Sexual Dysfunction - loss of interest in sex is common for people with MS. Males commonly find it difficult to reach or maintain an erection; they may also find it takes longer to ejaculate. Females may find achieving orgasm more difficult.


• Spasticity and muscle spasms - damaged nerve fibers in the spinal cord and brain can cause muscles to tightly and painfully contract (spasms). Muscles might get stiff and be resistant to movement (spasticity).


• Tremor - involuntary quivering movements


• Vision Problems - Double vision or blurring vision. There may be partial or total loss of vision, which usually affects one eye at a time. When the eye moves there is pain (optic neuritis, inflammation of the optic nerve)


• Gait - gait can be a problem for people with MS. Gait refers to the way you walk. MS can change the way people walk, because their muscles are weaker, they may have problems with balance and dizziness, plus fatigue.

These symptoms are less common, but also possible:

• Headache
• Hearing Loss
• Itching
• Respiration / Breathing Problems
• Seizures
• Speech Disorders
• Swallowing Problems
• Tremor

As the MS advances these symptoms may appear:

• Alterations in perception and thinking
• Fatigue
• Heat sensitivity
• Muscle spasm
• Sexual dysfunction

MS is an unpredictable disease. Each individual will experience it in different ways.. For some, MS starts with a subtle sensation, and it could take months and even years without any MS progression being noticed. For others, however, symptoms worsen much more rapidly - within weeks or months.

MS is very much an individual disease. People are encouraged not to compare what affects them against what other patients might experience.

The Four Courses Of Multiple Sclerosis

There are 4 courses of the disease. In each case, the MS may be mild, moderate or severe.

Relapsing-Remitting MS (RRMS): Over 80% of patients start off with this type.

• Relapsing - there are acute and unpredictable "exacerbations" (acute attacks, also called "flare-ups"). During this period symptoms get worse.
• Remitting - and then there are periods of full or partial recovery. Sometimes there is no recovery.
• The attacks may evolve over days or even weeks, and recovery can take weeks, or even months. In between the attacks there is calm, and symptoms do not worsen.

Primary-Progressive MS (PPMS): About 15% of patients have this type.

• There are no clear relapses or remissions.
• The progression of the disease is steady.
• It is the most common form of MS in those who develop the disease after 40 years of age.

Secondary-Progressive MS (SPMS):

• Starts off as a relapsing-remitting type of MS. Relapses and partial recoveries occur.
• However, in between cycles the disability does not go away.
• Eventually it becomes a progressive disease with no cycles.
• The progressive stage may start very early on, years, or even decades later.

Progressive-Relapsing MS (PRMS): The least common form.

• Symptoms worsen progressively, steadily
• There are acute attacks. Some recovery may follow, or may not.
• In the early stage, it seems the patient has primary progressive MS.

How Is MS Diagnosed?

It is still not yet possible to diagnose MS by sending samples to a lab or collecting physical findings.

The doctor needs to use several strategies to decide whether a patient meets the criteria for an MS diagnosis. To do this, other possible causes of the symptoms need to be ruled out.

The doctor will talk to the patient, carefully look at his/her medical history, carry out a neurolgic exam, order imaging scans, visual evoked potentials (VEP), spinal fluid analysis, and perhaps some further tests.

The health care professional needs to do the following before diagnosing MS:

• Detect evidence of damage in two or more separate parts of the CNS (central nervous system). The CNS includes the spinal cord, brain and optic nerves.
and

• Have proof that the CNS damage happened at least one month apart
and

• Eliminate other potential diagnoses

In 2001, the International Panel on the Diagnosis of Multiple Sclerosis revised the criteria to include precise instructions for using magnetic resonance imaging (MRI), visual evoked potentials (VEP) and cerebrospinal fluid analysis to hasten the diagnostic process. These tests can be used to look for a second area of damage in a person who has experienced only one episode of MS-like symptoms - referred to as a clinically-isolated syndrome (CIS). A person with CIS might not develop MS. The criteria were revised again in 2005 - it is now known as The Revised McDonald Criteria, and has improved the process.

Gauging MS progression through the patient's eyes

A person's multiple sclerosis progression can be determined by measuring how much their retina has thinned, researchers from Johns Hopkins MS Center reported in Neurology. The authors specified that a layer of the retina in the eyes thins when MS progresses.

The researchers wrote "This study suggests that retinal thinning, measured by in-office eye scans, called OCT, may occur at higher rates in people with earlier and more active MS."

What Are The Treatment Options For MS?

There is no cure for MS yet. Existing treatments focus on suppressing the autoimmune response and managing symptoms. Some MS patients do not need treatment because their symptoms are so mild, while others do.

The most common drugs used for treating MS; plus some new ones and a supplement that apparently does not help

• Corticosteroids - these drugs reduce inflammation. During a MS relapse inflammation can become problematic. Corticosteroids are the most commonly prescribed drugs for MS patients.
  
  Prednisone can be taken orally while methylprednisolone is administered intravenously.
  
  During a relapse there is a breakdown of the blood-brain-barrier (BBB) - harmful substances from the bloodstream might cross this barrier and make their way to the brain and spinal cord.
  
  Steroids stabilize the BBB and help prevent harmful substances leaking through. These drugs are also immunosuppressive - they help stop our body's immune system from attacking itself.


• Interferons - these medicines seem to slow down the progression of worsening MS symptoms. However, they must be used with care as they can also cause liver damage.
  
  Interferon alpha is used for treating some cancers, but has no effect on multiple sclerosis. Interferon gamma was also found to have no beneficial effect on multiple sclerosis. However, interferon beta has shown effectiveness as a multiple sclerosis treatment (A Canadian study contradicts this, see below). While the exact method by which interferon beta 1a achieves its beneficial effects in multiple sclerosis remains unknown, some researchers believe it may reduce inflammation. Studies looking at how interferon beta behaves in the lab suggest it may stop harmful cells from entering the brain. However, this is just a theory.
  
  Canadian scientists reported in JAMA in July 2012 that Interferon Beta may not slow long-term progression of MS. They had carried out a study with participants who had relapsing-remitting MS. They concluded that there was no clear evidence showing that Beta A had any measurable effect on the long-term disability progression of MS.


• Copaxone (Glatiramer) - this drug is aimed at stopping the immune system from attacking myelin. It is a combination of four amino acids (proteins). It is injected once a day, subcutaneously (under the skin). The patient may experience flushing and shortness of breath after receiving the injection.


• Tysabri (Natalizumab) - this drug is used on patients who either cannot tolerate other treatments or did not experience any benefits from them. It increases the patient's chances of developing multifocal leukoencephalopathy, a fatal brain infection. The drug is believed to work by reducing the ability of inflammatory immune cells to attach to and pass through the cell layers lining the intestines and blood-brain barriers.


• Mitoxantrone (Novantrone) - usually used only for patients with advanced MS. It is an immunosuppressant medication that can damage the heart.
  
  Novantrone was approved for the treatment of some cancer about 15 years ago. MS patients may find the idea of using chemotherapy cancer treatment disconcerting. In 2000 the Food and Drug Administration (FDA) approved Novantrone as the "only treatment for worsening MS". The recommended treatment schedule for Novantrone usage in MS is much less intensive than for cancer treatment.
  
  For MS patients whose illness is rapidly progressing and getting worse despite other therapies, Novantrone can help slow down the progression of disability and help preserve the patient's independence.


• Cannabis extract - a Phase III trial found that MS patients who took cannabis extract (tetrahydrocannabinol) had improvements in their symptoms of pain, muscle stiffness and insomnia.


• Aubagio (teriflunomide), a once-daily tablet for adults with relapsing forms of MS was approved by the FDA in September 2012. Clinical trials showed that those on Aubagio had relapse rates 30% lower compared to those on placebo.
• Do omega-3 fatty acid supplements help MS patients? - according to scientists at Haukeland University Hospital in Bergen, Norway, who carried out a double blind, placebo-control trial, omega-3 fatty acids do not help MS patients.

Rehabilitation

Rehabilitation is designed to help the MS patient improve or maintain his/her ability to perform effectively at home and at work. The focus is on general fitness and energy management, while at the same time dealing with the problems related to mobility and accessibility, speech and swallowing, memory, thinking and perception.

For an MS patient to achieve good quality health care, rehabilitation is usually a crucial component.

Rehabilitation programs generally include:

• Physical therapy (UK term is physiotherapy) - aims to provide people with the skills to maintain and restore maximum movement and functional ability.


• Occupational therapy - The therapeutic use of work, self-care, and play activities to increase development and prevent disability. It may include adaptation of task or environment to achieve maximum independence and to enhance the quality of life (American Occupational Therapy Association).


• Speech and swallowing therapy - professionals who are trained to assess speech and language development and to treat speech and language disorders are called Speech Language Pathologists, or Speech Therapists. They are also trained to help people with swallowing disorders.


• Cognitive rehabilitation - assists in the management of specific problems in thinking and perception. The patient learns and practices skills and strategies to improve function and/or make up for deficits that remain.


• Vocational rehabilitation - helps people with disabilities make career plans, learn job skills, get and keep a job.

Plasma exchange (plasmapheresis)

Plasmapheresis involves withdrawing whole blood from the patient. The plasma is removed from the blood and replaced with new plasma. Then the blood, with all its red and white blood cells is transfused back into the patient. This process is effective in treating patients with autoimmune diseases because it takes out the antibodies in the blood that are attacking parts of the patients body they should not be attacking.

However, whether plasmapheresis is of benefit to MS patients is unclear. Studies using plasmapheresis on patients with primary and secondary progressive MS have had mixed results.

Beware of fertility treatment - researchers from the Raúl Carrea Institute for Neurological Research in Buenos Aires, Argentina reported that females with MS who undergo ART (assisted reproduction technology) infertility treatment may risk increased disease activity.

Research Into Multiple Sclerosis

Over the last ten years, there has been a great deal of research into multiple sclerosis. Below are some examples:

Lemtrada (alemtuzumab), a medication used for the treatment of a type of leukemia, was shown to help MS patients in two Phase III trials. Lemtrada appears to "reboot" the immune system in MS cases that had not responded to first-line therapy; it reduced the risk of brain shrinkage and disability. Researchers from the University of Cambridge reported in the November 1, 2012, issue of The Lancet that alemtuzumab helped people with early MS who relapsed on previous treatments, as well as those who were treatment naïve (had not yet received any treatment).

Repairing Multiple Sclerosis Damage May be Possible - researchers at Oregon Health & Science University reported in Annals of Neurology (November 2012 issue) that they may be able to repair the damage to the central nervous system associated with multiple sclerosis by blocking an enzyme in the brain called hyaluronidase.

In animal experiments, the scientists blocked the activity of hyaluronidase in mice with MS-like disease, and found that myelin-forming cell differentiation was restored. In other words, remyelination (myelin repair) started to occur.

The authors added that the drug they used on the mice to block hyaluronidase activity would not work on humans, because of the serious side effects. However, they believe that creating one that is suitable for humans is feasible. Any therapy that promotes remyelination would completely change the lives of millions of MS sufferers around the world.

Nanoparticles to trick the immune system and protect the myelin sheath - researchers from Northwestern University Feinberg School of Medicine successfully used nanoparticles covered with proteins that tricked the immune systems of mice so that they stopped attacking myelin and halting MS progression. The mice had relapsing remitting MS.

The scientists say their breakthrough also has the potential for treatment for patients with type 1 diabetes, asthma, and other auto-immune diseases.

They reported in Nature Biotechnology (November 18th, 2012 issue) that MS relapses were prevented in mice for up to 100 days. In human terms, this is equivalent to several years.

The nanoparticles seem to be as effective as using the human body's own white blood cells to deliver the antigen. Phase I/II trials are currently underway on humans with MS. Nanoparticles are much cheaper and easier to use, the authors added.

BG-12 (dimethyl fumarate) - in September 2012, the results of two Phase III clinical trials that evaluated oral dimethyl fumarate, found that it may reduce relapses and disability progression in patients with relapsing-remitting MS.

Alzheimer's molecule reverses paralysis and inflammation - scientists from Stanford University School of Medicine found that a molecule known as the main culprit in Alzheimer's disease surprisingly reversed paralysis and inflammation in mice with multiple sclerosis.

Sodium accumulation - a French study revealed that sodium buildup is linked to MS disability. MRI scans detected the accumulation of sodium in certain parts of the brain among patients with early-stage MS, and throughout the entire brain in those with advanced MS. The scientists say sodium may be a biomarker for the degeneration of nerve cells that occurs in MS.

High Vitamin D levels protects mother but not baby from MS - pregnant women have a smaller risk of developing MS if their vitamin D levels are high. Scientists from Umeå University Hospital added that the developing fetus does not appear to receive the same protection if the mother's vitamin D levels are high. They reported their findings in the journal Neurology.

Jonatan Salzer, MD., neurologist and study author, said: "In our study, pregnant women and women in general had a lower risk for MS with higher levels of the vitamin, as expected. However, a mother's levels of vitamin D during early pregnancy did not have an effect on MS risk for her baby."

MS And Life Expectancy

The lifespan of a person with MS is usually about the same as a healthy person who does not have MS. In rare cases the MS may be so malignant that it is terminal.

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Nanoparticles Stop Multiple Sclerosis In Mice

A breakthrough new experimental treatment that uses nanoparticles covered with proteins to trick the immune system, managed to stop it attacking myelin and halt disease progression in mice with relapsing remitting multiple sclerosis (MS). The researchers say the approach may also be applicable to other auto-immune diseases such as asthma and type 1 diabetes.

Corresponding author Stephen Miller is the Judy Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine in Chicago in the US. He says in a statement:

"We administered these particles to animals who have a disease very similar to relapsing remitting multiple sclerosis and stopped it in its tracks."

"We prevented any future relapses for up to 100 days, which is the equivalent of several years in the life of an MS patient," he adds.

The study results suggest the nanoparticles are as effective as using patients' own white blood cells to deliver the antigen, an approach that is being tested in a phase I/II trial in MS patients. Using nanoparticles would be much cheaper and easier, say the researchers.

Miller and colleagues report their study, which was funded by the Myelin Repair Foundation, the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (NIH), and the Juvenile Diabetes Research Foundation, in the 18 November online issue of Nature Biotechnology.

Multiple Sclerosis (MS)

An auto-immune disease is where the immune system mistakenly attacks healthy tissue as well as clearing away harmful pathogens and cell debris. The type of tissue it attacks gives rise to different diseases.

In the case of Multiple Sclerosis (MS), the auto-immune target is myelin, the protein that forms the protective sheath that insulates nerve fibers in the brain, spinal cord and eyes and preserves the vital electrical signals they carry.

When the myelin is destroyed, the electrical signals can't travel, and the result is the characteristic symptoms of MS, which range from mild limb numbness to paralysis or blindness.

About 80% of MS patients have the relapsing remitting form of the disease, where there are periods of symptom flare-up (relapse) interspersed with periods where they stop (remit), either partially or completely.

Protein-Covered Biodegradable Nanoparticles Trick the Immune System

The researchers used biodegradable nanoparticles covered with myelin proteins or antigens to trick the immune system into treating myelin as "friendly". The nanoparticles are made from the same material as dissolvable stitches, except they are much smaller, about 200 times thinner than human hair.

For their study, they injected the nanoparticles, bearing their myelin antigen cargo, into mice bred to develop a disease similar to the human form of relapsing remitting MS.

The particles travelled to the spleen, a key immune system organ that removes unwanted materials such as old and dying cells from the blood, makes new blood cells and stores blood platelets.

Once in the spleen, the particles were engulfed by macrophages, white blood cells that literally gobble up and digest pathogens and unwanted materials and then send signals to other immune cells to target those materials.

But the effect in this case was to make the immune system view the nanoparticles as ordinary dying blood cells and nothing to be concerned about. This created immune tolerance to the myelin antigen by directly inhibiting the myelin responsive T cells. It also increased the numbers of regulatory T cells and further calmed the autoimmune response.

"Resets" Rather than Shuts Down Immune System

An attractive feature of this study is it shows a potential therapy that does not suppress the whole immune system as do current therapies for MS, which make patients more vulnerable to everyday infections and put them at higher risk for cancer.

Instead, the nanoparticles, with their myelin antigens, "reset" the immune system to normal. The result is it stops treating myelin as an alien invader and stops attacking it.

Christine Kelley, National Institute of Biomedical Imaging and Bioengineering director of the division of Discovery Science and Technology at the NIH, says:

"The key here is that this antigen/particle-based approach to induction of tolerance is selective and targeted. Unlike generalized immunosuppression, which is the current therapy used for autoimmune diseases, this new process does not shut down the whole immune system."

Biodegradable Material Is Already FDA Approved

The nanoparticles Miller and colleagues used are made of a polymer called Poly(lactide-co-glycolide) (PLG), which comprises lactic acid and glycolic acid, both natural metabolites in the human body. PLG is most commonly used for biodegradable sutures or dissolvable stitches.

Because PLG is already approved by the US Food and Drug Administration (FDA) for other uses, this should make it easier to get approval for using it to move this research from mice to human subjects.

The nanoparticles used in this study were developed by co-corresponding author Lonnie Shea, professor of chemical and biological engineering at Northwestern's McCormick School of Engineering and Applied Science.

The researchers tested different sizes of nanoparticles and found 500 nanometers was the best at resetting the immune response.

Potential for Treating Range of Auto-Immune Diseases

Miller says:

"The beauty of this new technology is it can be used in many immune-related diseases. We simply change the antigen that's delivered."

Shea and Miller are currently testing the nanoparticles to treat type 1 diabetes and airway diseases such as asthma.

Nanoparticles offer an attractive alternative to other approaches: they can be readily produced in a laboratory and standardized for manufacturing. This suggests therapies based on these mateials would be cheaper and more accessible to a general population.

Scott Johnson, CEO, president and founder of the Myelin Repair Foundation, says:

"The overarching goal is to ensure this important therapeutic pathway has its best chance to reach patients, with MS and all autoimmune diseases."

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