New molecule may lead to inflammation inhibitor

Scientists have developed a new drug-like molecule that can inhibit inflammation. The find has shown promise in preventing the progression of multiple sclerosis.

Walter and Eliza Hall Institute scientists have developed a small drug-like molecule called WEHI-345 that binds to and inhibits a key immune signaling protein called RIPK2. This prevents the release of inflammatory cytokines. Examining WEHI-345’s potential to treat immune diseases in experimental models of MS, it was found that WEHI-345 prevented further progression of the disease in 50 percent of cases after symptoms of MS first appeared.

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. Calling the results extremely important, researchers said WEHI-345 had potential as an anti-inflammatory agent.

The study’s lead author, Dr Ueli Nachbur, said institute scientists would use WEHI-345 to further investigate the signaling pathway that produced inflammatory cytokines and to develop a better, stronger inhibitor of RIPK2 for treating inflammatory disease. “This signaling pathway must be finely balanced, because WEHI-345 only delayed signaling rather than blocked it. Nevertheless, this delay is enough to completely shut off cytokine production,” he said.

The research was published in the journal Nature Communications.

Online Radio Station for MS is First of its Kind

MSFocusRadio.org offers 24/7/365 education, empowerment for MS community.

 

The Multiple Sclerosis Foundation (MSF) is proud to announce the launch of a new online radio station, MSFocus Radio. Found on the web at www.MSFocusRadio.org, or on mobile devices via a free app, this service of the MSF is a first of its kind for the MS community.

 

Featuring original content produced by the MSF in conjunction with our panel of healthcare experts, MSFocus Radio provides motivation, education, and empowerment to people affected by multiple sclerosis, 24 hours a day, seven days a week. MSFocus Radio is the MS resource that travels anywhere, thanks to free apps for both iOS and Android devices (available through iTunes and Google Play) provided by the MSF. 

 

Noting the station’s worldwide availability and round-the-clock scheduling, MSF Co-Executive Director Jules Kuperberg commented, “MSFocus Radio has dramatically broadened the scope of MSF's outreach both nationally and worldwide.”

 

To listen to MSFocusRadio or download the apps, visit www.msfocusradio.org now.

Teams Report Success Enhancing Myelin Repair in Mice Using Stem Cells and Other Novel Approaches

Two teams of researchers funded in part by the National MS Society report success in stimulating the repair of nerve-insulating myelin in mouse models of MS. Myelin is a major target of immune attacks in MS, and although these are early results and further work is needed, these findings show some promise for strategies to repair damage and restore function for people with multiple sclerosis.
Background: In MS, myelin, the material that surrounds and protects nerve fibers, is damaged in the brain and spinal cord, and so are the cells that make myelin, called oligodendrocytes. Though the replacement cells that could repair myelin, called oligodendrocyte precursor cells (OPCs), exist in the brain, in MS they cannot adequately repair the damaged myelin.
Stem Cell Study: Lu Chen, PhD, Thomas Lane, PhD (University of California, Irvine) and colleagues report that administering neural precursor cells (nerve stem cells) to mice with MS-like disease reduced inflammation, decreased myelin damage, and increased myelin repair.
The team injected the stem cells into the spinal cord of mice with an MS-like disease induced by a virus. Although the stem cells were rejected by the body, and were not detectable within eight days after transplant, they were effective nevertheless in reducing the disease. Improvements in motor abilities of the treated mice were still apparent after six months.
The team noted that improvements went along with an increase in a type of immune cell called “regulatory T cells,” or “Tregs.” To test whether the Tregs contributed to the improvements, they blocked Tregs activity, which reduced the stem cells treatments’ impact.
The team speculates that the stem cells may be stimulating the immune environment in a way that activates mouse OPCs, even though the stem cells themselves do not turn into myelin-making OPCs. They are now investigating this idea further to discover the factors released by the stem cells. Ultimately, this information could contribute to the development of stem cell therapies and even cell-free therapies that stimulate recovery in people with MS.
Stimulating Resident Cells: Jessica Williams, PhD, Robyn S. Klein, MD, PhD, and colleagues (Washington University School of Medicine) report that targeting a signaling receptor (docking site) called “CXCR7” on immature oligodendrocytes in mice enhances myelin repair.
Dr. Klein’s team focused on a messenger protein (chemokine) that interacts with the immature OPCs. They studied mice that were given a toxin called cuprizone, which mimics myelin damage that occurs in the brain during MS. Once cuprizone is withdrawn, myelin repair occurs. The team found that CXCR7 activity increased during myelin damage, and then reduced with myelin repair. When the team administered an experimental compound that inhibits CXCR7, the numbers of OPCs, as well as mature oligodendrocytes, increased within myelin-damaged areas. Myelin repair was enhanced.
These data suggest that CXCR7 might serve as an important therapeutic target to promote myelin repair. Since these studies were conducted in mice, further research is necessary to ultimately determine whether this approach might be an effective approach for stimulating myelin repair in people with MS.
Conclusion:  Achieving success in the Society’s priority area of nervous system repair would provide life-changing advances for people with MS.  

New Guideline from the American Academy of Neurology

The American Academy of Neurology, an association of neurologists and neuroscientists dedicated to promoting high-quality care for people with nervous system disorders, has released a guideline on the use of complementary and alternative medicine (CAM) in MS. The guideline was created by a panel of medical experts who evaluated all available published research studies. Through a comprehensive process, the panel carefully assessed the outcomes of relevant research studies, and also whether study findings could be generalized to the larger population of people with MS, and whether any safety concerns should be considered by physicians and patients who might use these treatments.
The widespread use of CAM by people with MS highlights the unmet need for more research and better therapies that will help people with MS live their best lives. Summaries of the guideline are available for patients and for clinicians.
Specific Guideline Information
Among studies of several forms of marijuana and its derivatives that were evaluated by the panel, the guideline reports that evidence suggests that:

• Oral cannabis extract and synthetic THC (tetrahydrocannabinol, a major active component of marijuana) are effective for reducing patient-reported spasticity and pain, but not MS-related tremor or spasticity measured by tests administered by the physician;
• Sativex oral spray (GW Pharmaceuticals) is effective for improving patient-reported spasticity, pain, and urinary frequency, but not bladder incontinence, MS-related tremor or spasticity measured by tests administered by the physician;
• Smoked marijuana research studies have not produced enough evidence to assess its safety or effectiveness for treating MS symptoms including spasticity, pain, balance, posture, and cognition.

Oral cannabis extract, THC and Sativex are not currently approved by the FDA for use by people with MS. The guideline notes that, as with any therapy, along with potential benefits come potential side effects, and for these cannabis derivatives the most commonly reported side effects were dizziness, drowsiness, difficulty concentrating and memory disturbance.
The guideline also points out that the long-term safety of marijuana use for MS symptom management is not yet known.
Read about the National MS Society’s position statement and more about the use of marijuana for MS symptoms.
Among other CAM therapy studies in MS evaluated by the panel, the available research evidence suggested that:

• ginkgo biloba is ineffective for improving cognitive function, but might reduce fatigue;
• magnetic therapy might reduce fatigue;
• reflexology might help ease unusual skin sensations such as tingling, but there is insufficient evidence to evaluate its potential for treating pain, fatigue, and other symptoms;
• the use of omega-3 fatty acids with low-fat diet to reduce relapses or disability, or improving quality of life is not supported by current evidence.

The guideline includes a table of all of the CAM therapies that were evaluated. For many of these, the panel concluded that there was not enough evidence from research studies to advise as to their effectiveness in treating MS or its symptoms. The guideline also indicates that there is little known about how CAM therapies interact in the body with each other or with disease-modifying therapies that individuals may be taking. The effects and side effects reported from non-MS studies were not evaluated.
While many people with MS report that they experience benefits from CAM therapies, this guideline confirms the need for more research to demonstrate the effectiveness of these treatment strategies. The National MS Society is committed to ensuring that no opportunity is wasted in our mission to stop MS progression, restore function lost to MS, and end MS forever so that people with MS can live their best lives. We have supported, and will continue to support, CAM research and will continue to advocate for additional government funding for CAM research.

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Multiple sclerosis cases hit 2.3 mln worldwide

(Reuters) - The number of people living with multiple sclerosis around the world has increased by 10 percent in the past five years to 2.3 million, according to the most extensive survey of the disease to date.

The debilitating neurological condition, which affects twice as many women as men, is found in every region of the world, although prevalence rates vary widely.

Multiple sclerosis (MS) is most common in North America and Europe, at 140 and 108 cases per 100,000 respectively, while in sub-Saharan Africa the rate is just 2.1 per 100,000, the Multiple Sclerosis International Federation's Atlas of MS 2013 showed on Wednesday.

The atlas also confirmed that MS occurs significantly more in countries at high latitude, with Sweden having the highest rate in Europe and Argentina having more cases than countries further north in Latin America.

The reason for the link to high latitudes is unclear but some scientists have suggested that exposure to sunlight may reduce the incidence of the disease.

The survey found a big increases in the number of medical experts trained to diagnose MS and help patients with treatment, while the number of magnetic resonance imaging (MRI) machines available to carry out scans has doubled in emerging countries.

But huge disparities remain when it comes to access to modern disease-modifying drugs.

MS medicine has seen a number of advances in recent years, particularly with the introduction of a new generation of oral therapies such as Novartis' Gilenya, Biogen Idec's Tecfidera and Sanofi's Aubagio.

These medicines offer an effective alternative to older disease-modifying treatments that are given by injection.

The survey found that injectable drugs like Biogen's Avonex and Teva's Copaxone were partly or fully funded in 96 percent of high-income countries, while Gilenya was available in 76 percent.

However, none of these drugs was available under government programmes in low-income countries. (Reporting by Ben Hirschler; Editing by Alistair Lyon)

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Unique type of immune cell contributes to multiple sclerosis (MS

Researchers at the National Institutes of Health have found evidence that a unique type of immune cell contributes to multiple sclerosis (MS). Their discovery helps define the effects of one of the newest drugs under investigation for treating MS — daclizumab — and could lead to a new class of drugs for treating MS and other autoimmune disorders.
In these disorders, the immune system turns against the body's own tissues. Ongoing clinical trials have shown that daclizumab appears to help quiet the autoimmune response in MS patients, but its precise effects on the legions of cells that make up the immune system are not fully understood.
The new study, published in Science Translational Medicine, shows that one effect of daclizumab is to thin the ranks of lymphoid tissue inducer (LTi) cells. These cells are known to promote the development of lymph nodes and related tissues during fetal life, but their role during adulthood has been unclear. The new study marks the first time that LTi cells have been implicated in any human autoimmune disorder.
"While further study is required to confirm the role of LTi cells in autoimmunity, our results point to the cells as a promising target for the development of new drugs to treat autoimmune disorders," said Bibiana Bielekova, M.D., an investigator at NIH's National Institute of Neurological Disorders and Stroke (NINDS).
Dr. Bielekova and her team found that among MS patients participating in clinical trials of daclizumab, the number of LTi cells was elevated in patients not receiving daclizumab compared to those on the drug. Patients receiving daclizumab also had reduced signs of inflammation in the cerebrospinal fluid (CSF) that surrounds the brain. And the researchers found that daclizumab appears to steer the body away from producing LTi cells, in favor of another cell type that counteracts autoimmunity.
In MS, the immune system attacks myelin, a material that insulates nerve fibers running throughout the brain and spinal cord. This typically leads to vision loss, and other sensory changes such as numbness and tingling, weakness, and fatigue. The disorder affects approximately 400,000 people in the United States. In about 85 percent of patients, MS starts as a relapsing-remitting form, in which symptoms come and go. Many patients eventually develop secondary progressive MS, in which symptom flare-ups are followed by worsening disability. Many medications are available to decrease the number of flare-ups, but no medication is effective at slowing the course of progressive MS.
The newer, sophisticated drugs for relapsing-remitting MS target key cells and molecules responsible for triggering and maintaining autoimmunity. Cytotoxic T cells, the immune system's specialized mobile infantry, are known to lead the attack. Antibodies, the immune system's guided missiles, appear to help reinforce it.
Daclizumab is a lab-engineered antibody, or monoclonal antibody, that alters signaling by interleukin-2 (IL-2), a key factor that mobilizes T cells. In a large clinical trial (NCT00109161), it has shown promise as an add-on therapy for patients taking the approved MS drug interferon-beta. Another ongoing trial (NCT00390221) is investigating whether or not daclizumab is effective as a stand-alone therapy for reducing relapses in MS.
The drug was designed to suppress T cell responses to IL-2, and it does so — but Dr. Bielekova had found previously that this suppression is indirect and depends on other immune cells. For example, one effect of daclizumab is to stimulate the non-specialized counterparts of T cells, called natural killer cells. These cells in turn suppress T cell activity.
In their new study, Dr. Bielekova and her team discovered that daclizumab's stimulatory effect on natural killer cells is paired with an inhibitory effect on LTi cells. They found evidence that the drug, via its effects on IL-2 signaling, acts on a type of stem cell. The drug appears to decrease the likelihood that this stem cell will develop into LTi cells, and sway it toward becoming natural killer cells.
"This helps explain why natural killer cells are activated and their numbers are expanded by daclizumab therapy," Dr. Bielekova said. Meanwhile, she said, the drop in LTi cells was "intriguing" in itself, given the cells' role in lymph node development.
Lymph nodes — found conspicuously in the armpits, neck and groin — are patches of tissue where T cells and antibody-producing B cells set up camp. Inside the nodes, T cells and B cells are found in clusters called lymphoid follicles, where they wait for a signal that the body is under siege from infection. In autoimmune disorders, abnormal lymphoid follicles can develop and contribute to the autoimmune response. Secondary progressive MS, in particular, is associated with abnormal lymphoid follicles in the connective tissues (or meninges) surrounding the brain. These are believed to contribute to chronic brain inflammation in MS, eventually leading to shrinkage of the brain.
Dr. Bielekova and her team reasoned that daclizumab, by suppressing LTi cells, should reduce the growth of lymphoid follicles. Since it is not possible to visualize these follicles in the live brain, the researchers measured the effects of daclizumab on markers of inflammation in the CSF. They found that CXCL13, a protein linked to lymphoid growth, and the IgG index, a measure of antibody production, decreased by an average of 50.4 percent and 13.5 percent, respectively, in trial participants who took the drug for six and half months.
"To our knowledge, no other MS therapy reduces IgG index," Dr. Bielekova said.
She cautioned that these data provide only an indirect link between LTi cells and brain inflammation in MS. If further research confirms that the cells play an important role in MS or other autoimmune disorders, "pursuing the development of new drugs to selectively inhibit LTi cells could be a useful therapeutic strategy," she said.
This study was funded by the NIH-NINDS intramural research program. The lead authors were Justin Perry and Sungpil Han. Mr. Perry was a fellow in NIH's Postbaccalaureate Intramural Research Training Award program, and is currently a Ph.D. student in the neuroscience program at Washington University in St. Louis. Mr. Han is an M.D.-Ph.D. student at Pusan National University in South Korea, and is supported in part by a fellowship from the Korea Research Foundation to study at NIH. Patient data were derived from a small completed trial (NCT00071838) which showed that daclizumab may reduce lesions in relapsing-remitting MS, and from an ongoing trial to investigate the drug's mode of action (NCT01143441).
NINDS (http://www.ninds.nih.gov) is the nation’s leading funder of research on the brain and nervous system. The NINDS mission is to reduce the burden of neurological disease – a burden borne by every age group, by every segment of society, by people all over the world.

Mom's Story

I am working on a second edition of Mom's Story, A Child Learns About MS. It will be at Amazon this fall.

Mom's Story

I am working on a second edition of Mom's Story, A Child Learns About MS. It will be at Amazon this fall.

Study Identifies Gene Linked to Vitamin D Deficiency

A recent study at Oxford University in England and published in Annals of Neurology, has identified a gene that causes vitamin D deficiency, a condition suspected of having a role in the development of MS.
The study examined the DNA of a group of people with MS who also have a large number of family members with the disease. All the DNA samples showed a distortion of the CYP27B1 gene which controls vitamin D levels in the body. And in a few rare cases where the DNA showed two copies of the distorted gene, the person was found to have a genetic form of rickets caused by vitamin D deficiency as well as MS.
The cause of myelin damage related to MS is still hotly debated: some believe it to be an autoimmune disease while others cite viruses or the environment as the culprit. There is growing evidence however of a correlation between MS and vitamin D deficiency. Epidemiological studies also show that populations closer to the equator and the sun, have far fewer case of MS than populations closer to the north or south poles. Researchers at Oxford University have now taken this premise a step further by showing that vitamin D deficiency and therefore possibly MS could have a genetic cause.
Despite this pivotal link, not all people with vitamin D deficiency develop MS. More research is needed to fully understand why. However, a distortion of the CYP27B1 gene is increasingly apparent in MS cases and it’s possible that the gene generates other, yet undetected, complications that lead to the disease—such as genetically caused rickets.
“Although vitamin D deficiency doesn’t always cause MS, it unveiled a critical genetic source that could be causing other problems that lead to MS,” says Jeffrey Epstein, whose foundation partially supported the study. “Even if we don’t understand all of the implications of that gene’s distortion, research can focus on gene therapy, and that will accelerate a cure.”
The study was partly funded by the National Multiple Sclerosis Society, The Wellcome Trust and the support of science investor, Jeffrey Epstein and The Jeffrey Epstein VI Foundation.

Company Decides Not to Seek Approval of Cladribine for MS

Merck Serono announced that it has decided not to pursue approval of its oral therapy Cladribine for the treatment of relapsing forms of multiple sclerosis. According to a company press release, discussions with the U.S. Food and Drug Administration made it apparent that the ongoing clinical trials of the therapy would not address the FDA’s requirements for approval. Details of these requirements have not been made public.


In March 2011, the company received a letter from the FDA indicating that its application for approval was not ready in its current form and outlining requirements for additional information. The company has stated that it plans to complete the current clinical trials and patient registry that are underway, and that results will be published.

“It’s disappointing that completion of the Cladribine trials will not lead to approval of a new therapy option for people living with MS,” says Dr. Timothy Coetzee, Chief Research Officer at the National MS Society. “However, thanks to the many people who participated in these clinical trials, results from these studies will add to the body of knowledge about MS and should help spur new leads toward stopping MS, reversing its damage and ending MS forever.”

Additional therapies, including oral therapies, are currently making their way through the development pipeline.

Scientists Reverse Multiple Sclerosis in Mice

Experimental treatment suppresses immune cells, forcing remission, study says

By Robert Preidt

.WEDNESDAY, Aug. 12 (HealthDay News) -- An experimental treatment that suppresses the immune system to put multiple sclerosis into remission completely reversed the disease in mice, Canadian scientists say.

In MS, the immune system attacks the central nervous system. 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.

"GIFT15 can take your normal, run-of-the-mill B-cells and convert them ... into these super-powerful B-regulatory cells," study team leader Dr. Jacques Galipeau, of the Jewish General Hospital Lady Davis Institute for Medical Research and McGill University in Montreal, said in a university news release.

He and his colleagues took normal B-cells from mice and sprinkled GIFT15 on the B-cells. "And when we gave them back intravenously to mice ill with multiple sclerosis, the disease went away," Galipeau said.

The treatment was fully effective with a single dose, and no significant side effects were seen in the mice, the researchers reported.

Their findings were published online Aug. 9 in Nature Medicine.


More information

The U.S. National Institute of Neurological Disorders and Stroke has more about multiple sclerosis.

Read more: http://www.healthline.com/healthday/scientists-reverse-multiple-sclerosis-in-mice#ixzz1IycEpuL5

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Visit me and pickup a copy of Mom's Story at the Second Annual Disability Empowerment Center (DEC) Health and Wellness Fair, April 9, 9:00-4:00.