The Forest Whispers My Name III » MS

Multiple Sclerosis May Cause Changes in Thalamus: Study

pmb — Fri, 30 Dec 2011 23:57:27 +0000

(HealthDay News) — New research suggests that in addition to the disabling lesions it’s known to cause, multiple sclerosis also damages the part of the brain that affects thinking skills, motor function and the senses.
“The thalamus is a central area that relates to the rest of the brain and acts as the ‘post office,’” study co-author Khader Hasan, an associate professor at University of Texas Health Science Center at Houston, said in a university news release. “It also is an area that has the least amount of damage from lesions in the brain, but we see volume loss, so it appears other brain damage related to the disease is also occurring.”

Hasan and colleagues published their observations in a recent issue of the Journal of Neuroscience. The study authors noted that aging alone can bring about changes in the size of the thalamus region, resulting in some shrinkage after age 70. However, the research team wanted to see if multiple sclerosis (MS) — which is often associated with the onset of dementia — accelerates such structural shifts.

The radiology researchers used cutting-edge MRI scanning equipment to analyze brain structure in 109 MS patients, compared to 255 healthy men and women. The result: MS patients had greater volume loss in the thalamus region than healthy patients, after accounting for age. And the greater the loss in thalamus volume, the more disabled the patient was, the investigators noted.

“This is looking at multiple sclerosis in a different way,” Hasan said in the news release. “The thalami are losing cellular content and we can use this as a marker of what’s going on. If we can find a way to detect the disease earlier in a more vulnerable population, we could begin treatment sooner.”

Teriflunomide is as effective as interferon beta 1a in reducing relapse rate

pmb — Mon, 26 Dec 2011 13:58:58 +0000

A study comparing teriflunomide with beta interferon 1a (Rebif) has found that the two drugs had a similar effect on relapse rates and that teriflunomide was safe and generally well tolerated. The two year TENERE study involved 324 people with relapsing remitting MS taking one of two doses of teriflunomide or Rebif.

A two year phase III study previously, compared two doses of teriflunomide with placebo in 1,088 people with relapsing remitting MS. Both doses of teriflunomide reduced relapse rate by about 31% compared to placebo. The higher dose (14mg daily) reduced the risk of disability progression (sustained for 12 weeks) by 30%.

Terilunomide (Aubigo) is an oral formulation and an application is expected to be filed in early 2012 to licence the drug in Europe.

Sanofi’s Multiple Sclerosis Drug Disappoints – Analyst Blog

pmb — Sat, 24 Dec 2011 03:59:29 +0000

Sanofi’s subsidiary,Genzyme , recently announced disappointing top-line results of its phase III candidate,Aubagio (teriflunomide ).

Results were presented from the phase IIITENERE trial, which was conducted on 324 patients with relapsing forms of multiple sclerosis (RMS ).

Aubagio failed to show statistical superiority over Pfizer/MerckKGaA’s Rebif . Results showed that 48.6% and 37.8% of patients receiving 7 mg and 14 mg of Aubagio respectively achieved the primary endpoint as compared to 42.3% of patients receiving Rebif , over a two-year period.

However, both doses of Aubagio were found to be safe and well tolerated. Sanofi plans to present detailed data from the phase III TENERE trial at an upcoming medical meeting.

TENERE is the second completed study evaluating the efficacy of Aubagio in RMS patients. In October 2010, Sanofi had announced positive results onAubagio from a pivotal phase III study (TEMSO) in patients withRMS .

There are three more studies in progress, namely TOWER, TOPIC and TERACLES which makes the program one of the largest and broadest amongst any oral multiple sclerosis agent under development.

Competition in the oral MS market will be intense and Aubagio needs to demonstrate superior efficacy and tolerability to gain share.

Novartis’ Gilenya already has a lead in the oral MS market with the product being approved in September 2010.

Another major competitor could be Biogen Idec’s BG-12, which has shown encouraging data so far.

In such a scenario and given the TENERE data, Aubagio, if approved, will most likely generate modest sales.

Aubagio is currently under regulatory review in the US with the EU filing slated for the first quarter of 2012.

Daily pill could stop or even reverse multiple sclerosis

pmb — Sun, 25 Sep 2011 11:57:13 +0000

Doctors have made an ‘exciting’ breakthrough that could lead to a new treatment to stop – or even reverse the symptoms – of multiple sclerosis.

Researchers have discovered that people with MS have significantly lower levels of brain chemicals called neuro-steroids.

Neuro-steroids help build brain cells and maintain their function, connecting different areas of activity in the brain.

Scientists and neurologists at the University of Alberta in Edmonton, Canada believe that it would be possible to replace the missing chemical with a daily pill that would represent a completely different way of dealing with the disease.

Dr Chris Power announced the discovery in a research paper in the latest issue of Brain.

He said: ‘This frankly is an exciting breakthrough and has huge potential. The role of neurosteroids in the brain has been known for some time but no one thought – until now – that they might play a role in MS.’

The link with the disease was made when his team tested the brains of 16 patients from Alberta – which has the highest levels of MS in the world – and discovered that they had significant lower levels of a particular neuro-steroid allopregnanolone compared to a group of patients who had died from other diseases.

‘The chemical is already available which speeds up the process that could eventually get this into humans with MS,’ he said.

Researchers are interested in the vitamin D link because it has been established that there are higher levels of MS in Northern areas of the world such as Scotland where reduced levels of the vitamin have been linked to less exposure to sunlight.

When mice with MS were treated with allopregnanolone it had a significant effect, reducing inflammation levels in the brain and repairing nerve fibres.

In MS the myelin sheath around nerves is destroyed by the disease which is triggered by the immune system ‘over reacting’ and attacking healthy cells rather than invading infections and diseases.

MS in its severest form can cause loss of mobility but the Canadian researchers found that the mice given the steroid were found to have increased levels of mobility over a 30 day period following the start of treatment.

Dr Power said: ‘Overall we found that the mice showed a 50 per cent reduction in MS disease severity in the brain.’

At present there a number of drugs that slow the progression of MS but after a period of time many patients ‘fail’ on the treatments and their disease continues to progress.

Dr Power believes that regular treatment with allopregnanolone – and possibly other neurosteroids halt the disease and can reverse some of the symptoms.

He said: ‘We were surprised by our initial discovery that this neurosteroid was present in reduced levels in MS patients and then amazed to discover that when we used it as treatment it had such significant effects.’

Funding for the research came from the Canadian Government and the country’s MS Society.

Dr Power is now hoping to get Government or drug funding to start the first stages of human trials with allopregnanolone within the next couple of years.

He said: ‘Initially we will be looking that it is safe to take. But to some extent that work has been done because of the trials in other disease areas. Our research on mice showed no toxicity.

‘If we overcome that hurdle – which we should then we would be onto stage two trials to establish that it works as a treatment.

‘We are talking about it being at least six or seven years away as a treatment but I am optimistic about our chances even though there are a number of hurdles to overcome.’

Research Identifies How Vitamin D Combats MS

pmb — Wed, 17 Aug 2011 10:07:59 +0000

Mechanism suggests a potential new path toward pharmaceutical treatment of MS, as well as therapies for other autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, eczema and psoriasis.

For years scientists have noted an association between levels of vitamin D in a person’s body and the person’s ability to resist or minimize the effects of multiple sclerosis (MS) but didn’t understood the mechanism involved. Until now.

New breakthrough research by a collaborative team at UMDNJ-New Jersey Medical School and Stanford indicates that vitamin D directly terminates the production of a disease-causing protein.

As the investigators outline in their report, published in the September issue of Molecular and Cellular Biology (“1,25-Dihydroxyvitamin D3 ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A” ):

• During MS (“EAE” in mice), a damaging protein called interleukin-17 (IL-17) is produced by immune cells in the brain.

• The research team found that after vitamin D binds to its receptor, the receptor parks itself on the gene that encodes IL-17.

• By doing so, the vitamin D receptor occupies a site normally reserved for a protein called NFAT, which is required to turn the IL-17 gene on.

• The gene stays off and IL-17 levels plummet.

• At the same time, the vitamin D receptor turns on another gene, whose product generates suppressive T cells that combat the destructive action of their IL-17-producing counterparts.

According to the researchers, led by UMDNJ Prof. Sylvia Christakos, PhD, the mechanism they identified suggests what might be a new path toward pharmaceutical treatment of MS, as well as therapies for other autoimmune diseases that might include rheumatoid arthritis, type 1 diabetes, eczema and psoriasis.

Overactive Immune Response Silenced By New Anti-Inflammatory Agents

pmb — Wed, 17 Aug 2011 08:14:17 +0000

A new way to fight inflammation uses molecules called polymers to mop up the debris of damaged cells before the immune system becomes abnormally active, researchers at Duke University Medical Center report.

The discovery, published in the journal Proceedings of the National Academy of Sciences, offers a promising new approach to treat inflammatory auto-immune disorders such as lupus and multiple sclerosis, which are marked by an overactive immune response. “Depending on the disease, cells that are damaged drive or perpetuate the immune response,” said Bruce A. Sullenger, Ph.D., director of the Duke Translational Research Institute and senior author of the study.

“We have shown that we can inhibit that process.” Sullenger said the idea for the new approach stems from earlier findings by Duke scientists and others that dying and diseased cells spill nucleic acids – the building blocks of life that include DNA and RNA – that then circulate at high levels in the bloodstream.

While DNA and RNA inside the cell regulate important functions such as growth and division, outside of cells in the blood, these nucleic acids serve as powerful signals to the immune system that something is amiss. Once activated, the immune system launches an attack to fight whatever caused the cell damage, whether an infection or toxic substance. Under normal circumstances, this inflammatory response eventually restores order. In some cases, however, the inflammatory response becomes persistent and out of control, leading to tissue damage and causing symptoms such as fever and pain. Chronic inflammation has been implicated in lupus, multiple sclerosis, obesity, psoriasis, irritable bowel syndrome, arthritis and numerous other maladies.

The Duke scientists, working to interrupt this cycle, focused on a set of molecules called nucleic acid binding polymers that were designed to infiltrate the nucleic acid inside of cells and deactivate specific immune triggers. “Then we had a ‘eureka moment,’” Sullenger said.

“Because the inflammatory nucleic acids are outside of cells, whereas DNA and RNA normally function inside cells, we realized that the polymers could bind to the external nucleic acids without disrupting intracellular functions of DNA and RNA.” It was a simple mop-up approach, and it worked as planned in experiments on mice: “We could use the polymers as molecular scavengers – sponges to go around and soak up and neutralize those inflammatory nucleic acids so the immune system doesn’t recognize them and go into the overdrive of inflammation,” Sullenger said.

David S. Pisetsky, M.D., Ph.D., a rheumatologist at Duke and co-author of the study, said the anti-inflammatory approach has numerous potential applications, not only for auto-immune disorders, but also for the acute tissue damage of severe bacterial and viral infections, shock and injuries.

“One setting to test the effects of the polymers involves acute events such as injuries, where it may be easier to measure the presence of the nucleic acids in the blood and the effects of polymer binding,” Pisetsky said, adding that the long-term safety of the new anti-inflammatory approach in humans remains unknown. Sullenger said patents have been filed on the finding, and the team is pressing ahead to develop therapies. “At some level we’ve opened up this huge treasure chest of opportunities and now we have to figure out which way to go,” he said.

In addition to Sullenger and Pisetsky, study co-authors include: Jaewoo Lee; Jang Wook Sohn; Ying Zhang; and Kam W. Leong. The study was funded in part by the National Heart, Lung and Blood Institute. The researchers reported no conflicts of interest.

Major genetic study of Multiple Sclerosis reveals DNA hot spots of disease susceptibility

pmb — Mon, 15 Aug 2011 21:58:20 +0000

Enlarge

Multiple sclerosis (MS) is a complex disease that is not caused by a single gene or environmental factor. Rather, many overlapping causes contribute to the disease, as shown here. These may include the action of various genes and exposure to chemicals, pathogens, and other external triggers. The study of epigenetic and other regulatory mechanisms linked to MS susceptibility is only beginning to emerge. Credit: J.Oksenberg/UCSF.

Genetic secrets of multiple sclerosis may be buried in 50 “hot spots” in the human genome, which were just uncovered by a consortium of more than 240 scientists in 23 countries.

MS Research Doubles Number Of Genes Associated With The Disease, Increasing The Number To Over 50

pmb — Fri, 12 Aug 2011 08:16:34 +0000

Dr. John Rioux, researcher at the Montreal Heart Institute, Associate Professor of Medicine at the Université de Montréal and original co-founder of the International Multiple Sclerosis Genetics Consortium is one of the scientists who have identified 29 new genetic variants linked to multiple sclerosis, providing key insights into the biology of a very debilitating neurological disease. Many of the genes implicated in the study are relevant to the immune system, shedding light onto the immunological pathways that underlie the development of multiple sclerosis.

The research, involving an international team of investigators led by the Universities of Cambridge and Oxford, was published Aug 12th in the journal Nature. This is the largest MS genetics study ever undertaken and includes contributions from almost 250 researchers as members of the International Multiple Sclerosis Genetics Consortium and the Wellcome Trust Case Control Consortium.

Multiple sclerosis is one of the most common neurological conditions among young adults, affecting around 2.5 million individuals worldwide. The disease results from damage to nerve fibres and their protective insulation, the myelin sheath, in the brain and spinal cord. The affected pathways – responsible in health for everyday activities such as seeing, walking, feeling, thinking and controlling the bowel and bladder – are prevented from ‘firing’ properly and eventually are destroyed. The findings announced today focus attention on the pivotal role of the immune system in causing the damage and help to explain the nature of the immune attack on the brain and spinal cord.

In this multi-population study, researchers studied the DNA from 9,772 individuals with multiple sclerosis and 17,376 unrelated healthy controls. They were able to confirm 23 previously known genetic associations and identified a further 29 new genetic variants (and an additional five that are strongly suspected) conferring susceptibility to the disease.

A large number of the genes implicated by these findings play pivotal roles in the workings of the immune system, specifically in the function of T-cells (one type of white blood cell responsible for mounting an immune response against foreign substances in the body but also involved in autoimmunity) as well as the activation of ‘interleukins’ (chemicals that ensure interactions between different types of immune cell). Interestingly, one third of the genes identified in this research have previously been implicated in playing a role in other autoimmune diseases (such as Crohn’s Disease and Type 1 diabetes) indicating that, perhaps as expected, the same general processes occur in more than one type of autoimmune disease.

Previous research has suggested a link between Vitamin D deficiency and an increased risk of multiple sclerosis. Along with the many genes which play a direct role in the immune system, the researchers identified two involved in the metabolism of Vitamin D, providing additional insight into a possible link between genetic and environmental risk factors.

Dr. Alastair Compston from the University of Cambridge who, on behalf of the International Multiple Sclerosis Genetics Consortium, who led the study jointly with Dr. Peter Donnelly from the Wellcome Trust Centre for Human Genetics, University of Oxford, said: “Identifying the basis for genetic susceptibility to any medical condition provides reliable insights into the disease mechanisms. Our research settles a longstanding debate on what happens first in the complex sequence of events that leads to disability in multiple sclerosis. It is now clear that multiple sclerosis is primarily an immunological disease. This has important implications for future treatment strategies.”

Dr. Donnelly added: “Our findings highlight the value of large genetic studies in uncovering key biological mechanisms underlying common human diseases. This would simply not have been possible without a large international network of collaborators, and the participation of many thousands of patients suffering from this debilitating disease.”

Dr. John Rioux, holder of the Canada Research Chair in Genetics and Genomic Medicine, furthermore stated that “the integration of the genetic information emerging from studies of this and other chronic inflammatory diseases such as Crohn’s disease, ulcerative colitis, arthritis and many others is revealing what is shared across these diseases and what is disease-specific. This is but one of the key bits of information emerging from these studies that will guide the research of disease biology for years to come and be the basis for the development of a more personalized approach to medicine.”

As Archie Bunker would say: “you STUPID woman!” – Second reported death after controversial MS treatment

pmb — Tue, 12 Jul 2011 00:30:14 +0000

You really have to be really dumb to still believe that italian hoax.

A Calgary woman has died in the United States following controversial neck vein surgery to treat her multiple sclerosis. Maralyn Clarke died April 18, shortly after undergoing treatment at Synergy Health Concepts Inc. in Orange County, Calif.

She becomes the second victim of the vein procedure, almost a year after Mahir Mostic of St. Catharines, Ont., died in October 2010 following a similar operation in Costa Rica. The treatment is based on a procedure developed by Italian Dr. Paolo Zamboni, whose research suggests that multiple sclerosis may be associated with vascular problems.
Clarke, 56, flew to California on April 13 in search of a cure for an illness she had lived with for years. Her husband, Frank Lamb (unavoidable pun will follow), said his wife experienced severe headaches, nausea and vomiting a few hours after being discharged and was taken to a nearby hospital. She was taken off life support on April 18.

“I think they discharged her before she could make full recovery,” he said Friday, adding that her blood pressure was still high when she left the facility.
Clarke’s final diagnosis included irreversible brain injury, according to her medical records. Officials at the Synergy Health Concepts refused to comment on the case, saying state laws prevent them from sharing confidential information regarding their patients.
Because Zamboni’s treatment —— which uses angioplasty or ballooning to open blocked neck veins — is not available in Canada, a number of CCSVI patients have opted for going overseas for treatment.
Since the procedure was first introduced, it has raised heated controversy among physicians as well as in the general public. Some argue there is a risk of provoking a stroke if the vein surgery is not properly carried out. Experts say there should be rigorous studies to assess whether the procedure works and is safe. But those who have already allegedly been victims to the operation will hardly find any solace.

“It’s been tough, very tough,” said Lamb, referring to life since his wife’s death. “And every time somebody else calls, it gets tougher.” – maybe he should have thought of that before allowing his wife to go on a suicide trip. Oh wait, he is a LAMB, after all. Duh…

Current Mood: Annoyed & blah & Alarmed

Biogen Idec study reveals potential new multiple sclerosis treatment approach

pmb — Fri, 08 Jul 2011 13:12:45 +0000

Biogen Idec, a leader in the research and development of treatments for people with Multiple Sclerosis (MS), announced results from a study that suggest that inhibiting death receptor-6 (DR6) function may represent a novel approach in the treatment of multiple sclerosis by blocking autoimmune response while promoting remyelination. Data from in vitro and in vivo models were published online and will be published in the July print issue of Nature Medicine.

“Our approach to finding new treatments for this complex disease looks beyond known pathways affected by current MS treatments,” said Sha Mi, Ph.D., distinguished investigator, neurobiology research, Biogen Idec. “Our in vivo and in vitro studies demonstrate that inhibiting or blocking DR6 function results in robust axonal remyelination. These data provide strong evidence that this targeted approach warrants further research and ultimately may lead to an important new way of treating demyelinating diseases, including MS.”

MS affects each person differently, and more treatment options that target multiple pathways are needed in order to meet the various needs of patients. This study is the first-ever to demonstrate the negative role that DR6 plays in regulating remyelination within the central nervous system. Equally important, the data support the development of DR6 antagonist as a treatment for MS, a neurodegenerative disease that contains both autoimmune and demyelination components. The dual role of DR6 antagonists in promoting remyelination and inhibiting autoimmune activation represents a novel approach for the treatment of multiple sclerosis and other central nervous system diseases that result from demyelination.
“Until we find a cure, Biogen Idec is dedicated to driving ground-breaking research and pursuing highly differentiated therapies for the treatment and management of MS and other central nervous system diseases,” said Douglas E Williams, executive vice president, research & development, Biogen Idec. “No currently approved MS treatment targets DR6, and the identification of the potential role of this receptor illustrates the breadth of our ongoing commitment to using cutting-edge science to discover of potential new treatment options for the MS community.”