GlaxoSmithKline had an investor update yesterday which mentioned a novel new MS drug in their pipeline. In laymen''s terms, this is an ORAL (!) drug whose activity is comparable to Antegren. It''s also interesting to see that GSK, who currently does not offer an MS therapy, is calling Antegren "the latest advance in the treatment of the disease" even though Antegren has not achieved regulatory approval yet, and in spite of all the cautions the other MS drug manufacturers have made against Antegren. Politics make strange bedfellows?

In any case, this drug, with the glamorous name "683699" is currently in Phase IIb trials (dosing) and is targeted for availability in 2008. Again, for those of you that hate needles (all of you?), the end looms near as many major new MS drug studies now are focusing on oral therapies (e.g., Teva''s laquinimod).

"Today GlaxoSmithKline gave investors and financial analysts an update on its compounds in development to treat Central Nervous System disorders, a therapy area that represents approximately 20% of the company''s total R&D pipeline...

-- New compounds have significant potential to fight neurodegenerative and psychiatric diseases, including the first oral integrin antagonist for multiple sclerosis, novel treatments for Alzheimer''s disease and schizophrenia, and new mechanisms to treat depression and anxiety...

683699, being developed in collaboration with Tanabe, is expected to be the first oral integrin antagonist for the treatment of multiple sclerosis. In a recent study, oral ''699 matched the biomarker activity of intravenous Antegren - the latest advance in the treatment of the disease. The compound is in Phase IIb with filing expected in 2008."

Click "read more" for the full story...

A few months ago, our community member Finn wrote an excellent article on the state of MS treatments today called "Is it a Boomerang or What? Controversial Thoughts on MS Research." Today, we are proud to post his second editorial entitled, "How much for the Hope?" discussing the obstacles in the way of formal approval for drugs showing great promise as treatments for MS, but originally developed to treat other conditions, such as high cholestorol and acne. Finn posits that these affordable, readily-available alternatives, such as statins and LDN, pose a threat to the standard CRABs and their establishment, introducing further difficulties in getting them evaluated and approved.

Again, we issue a big "thank you" to Finn and extend an invitation to all of our community members to prepare articles on topics important to them-- we will be extremely happy to share them with the rest of the community.

Now, the article:

"At the moment there are four drugs in clinical use that are developed for MS, three beta interferons (Avonex, Betaferon/Betaseron, Rebif) and glatiramer acetate (Copaxone). Together they are known as the ABCRs. They are all expensive, injectable drugs with potentially severe side effects. For almost ten years now they have been recommended as a first line treatment for relapsing-remitting MS by both neurologists and MS-societies around the world. Those recommendations have often been supported with sales promotion material and results from clinical trials funded by the drug companies.

Recently things have been starting to change. There have been doubts about the effectiveness of ABCRs almost as long as they have been used, but within the last two years researchers have been able to demonstrate that even oral drugs commonly used to treat high cholesterol (simvastatin) and acne (minocycline) could be as effective as - or even more effective than - the ABCRs in treating MS. There is also a growing amount of anecdotal evidence on the internet that the opiod antagonist naltrexone taken in low doses (LDN) has relieved MS-symptoms in many individuals. So it is understandable that the manufacturers of the ABCRs and some of the instances funded by them have started to fight back against this kind of development. In doing so they are using three major arguments..."

Click "read more" to read this great editorial

Very promising new study on combination therapy of IFN-beta (e.g., betaseron) with a human antibody called "daclizumab"... Of course, the usual "larger studies are needed" applies, particularly since this one was only on eleven patients! However, it is very interesting that they are talking not only about reduction of lesions, but also of "significant clinical improvements" which is what we''re really aiming for with MS treatments...

"A small clinical trial of patients with multiple sclerosis (MS) who did not respond to interferon alone found that adding the human antibody daclizumab improved patient outcome. Patients who received the combined therapy had a 78 percent reduction in new brain lesions and a 70 percent reduction in total lesions, along with other significant clinical improvements.

Ten patients showed a dramatic reduction in both the severity and number of brain lesions as demonstrated by magnetic resonance imaging. The decrease in new lesions, as well as the total decrease in lesions, occurred gradually over a 2-month span. Improvement was also seen on a neurological rating scale and in a test of hand function. The clinical improvement was unexpected in such a small trial, since a larger number of patients is usually required to show clinical effects. One patient with extremely high inflammation activity responded initially to daclizumab but, as disease activity returned, was given higher doses of the antibody and was excluded from final analysis.

''While these results are preliminary, this discovery offers hope for thousands of patients with ertain forms of MS. Findings like this are helping us to better understand how this disease affects the immune system, which offers hope for all MS patients,'' said Story C. Landis, Ph.D., NINDS director."

Click "read more" for the full article...

This study is just a summary of the work done in remyelination, but its conclusion reflects what is quickly becoming the accepted strategy to treat MS in the future: a multi-modal approach tailored to an individual''s particular MS designation. Much work let to be done in this field obviously, but it''s good to see that this general approach is starting to be adopted.

"Remyelination has been seen in up to 70% of lesions but repair is generally incomplete. The demonstration of neuropathological heterogeneity of MS lesions suggests different pathophysiological subtypes and it is therefore unlikely that there is a uniform cause of incomplete remyelination in MS...

More information on the pathogenesis of MS, the reason why repair mechanisms fail in MS and a better understanding of the regulation of remyelination are required. This will ultimately lead to a specific treatment tailored for the individual patient and will probably involve a combination of immunomodulation, remyelination and neuroprotection."

Click "read more" for the full abstract...

This is the first time we''ve heard about fibrin being a possible causative factor in MS... the mention of snake venom as a possible treatment is also rather interesting...

"Tissue damage due to Multiple Sclerosis (MS) is reduced and lifespan lengthened in mouse models of the disease when a naturally occurring fibrous protein called fibrin is depleted from the body, according to researchers at the University of California, San Diego (UCSD) School of Medicine...

However, the research team cautions that fibrin plays an important role in blood clotting and systemic fibrin depletion could have adverse effects in a chronic disease such as MS. Therefore, additional research is needed to specifically target fibrin in the nervous system, without affecting its ability as a blood clotting protein...

... the researchers tested drug-induced fibrin depletion, which was accomplished by administering ancrod, a snake venom protein, to the transgenic mice. Consistent with the genetics-based experiments, the pharmacological depletion also delayed the onset of inflammatory myelin destruction and down-regulated the immune response. Previous studies by other investigators who used ancrod in experimental autoimmune encephalomyelitis (EAE), another animal model of MS, also showed amelioration of neurologic symptoms."

Please click "read more" to get the full article... 

We are extremely proud to present the following article, written by our very own community member, Finn. In it, Finn broadly discusses current MS research and its implications on possible causes and therapies. Finn also critically analyzes the standard CRAB treatments in light of new developments. The author has spent a great deal of time poring over the literature, and this read is enlightening and informative.

This is MS is an entirely unbiased site, and we want to encourage all of our members to feel free to share their thoughts about MS with us and the community at large. MS is receiving a great deal of attention in the medical field, and piecing together the various studies to create a cohesive theory, as Finn has done, is an extremely helpful task. We welcome submissions from all of our community members-- if there''s a topic that interests you, please send us a note and we''d be happy to work with you to pull it together and get it published.

Without further ado, the article:

"Consensus opinion is that MS-research has been progressing rapidly during the past ten years. As an MS-sufferer myself I would like to believe it. But if the amount of research projects is compared to the results achieved so far, one might want to ask oneself if there have been any major breakthroughs during that time..."

Please click "read more" to read the entire piece.

This abstract is short on details but shows that research is coming to grips with the idea that MS is not simply a malfunction of the immune system and instead involves direct damage to the brain. Protecting the brain, which right now can be achieved at least partially with antioxidant supplementation and a careful diet/environment (e.g., no smoking, regular exercise, etc)

"In the past, neuroprotective therapies were mostly explored in neurodegenerative disorders like Parkinson''s and Alzheimer''s disease, and in ischaemic stroke.

More recently, however, neuroprotection has been proclaimed an important goal for multiple sclerosis (MS) therapy.

The basis for widening the scope of neuroprotection is evidence that neuronal and axonal injury are key features of MS lesions.

In contrast with degenerative and ischaemic central nervous system injury, however, neurodegeneration in MS appears to be caused by an inflammatory, presumably autoimmune, process.

The challenge for neuroprotection in MS is therefore greater than in degenerative and ischaemic disorders, because MS requires the combination of neuroprotective therapy and effective immunomodulation."

Click "read more" to retrieve the references...

This is a tantalizing story about a new drug being trialed at the Mayo Clinic-- but there is no information about what this drug is and our preliminary searches could not locate any either. If any of our more industrious members would like to do some digging, we''d be much obliged. For now, here''s what we have:

"Multiple sclerosis often strikes without warning, many times attacking people in their 20s and 30s. Now, researchers at the Mayo Clinic are testing a new drug to see if it might be able to prevent many of the debilitating symptoms of MS from ever developing, KMBC''s Kelly Eckerman reported...

It''s too early to know for sure if the new drug may stop the damage from progressing, but Dr. Dean Wingerchuk, a Mayo neurologist, seems hopeful.

"If we treat very aggressively early in the disease, and get rid of as much inflammation as possible, we will be able to delay or, perhaps even, in some people, prevent the nerve degeneration -- the progression that occurs down the road," Wingerchuk said."

Click "read more" for the rest of the article...