Controversial treatment for MS - and another angle for research of IBD

I don't know much about multiple sclerosis, but I see articles about it all the time as I monitor news about autoimmune diseases. I came across an article about a controversial treatment for MS that a person in Britain couldn't get because it hasn't been officially sanctioned by the government yet via clinical trials. For a person with IBD, I found the treatment less interesting than what it suggests about the potential cause of the disease.

Here's a really short excerpt just to give you an idea:

In 2005, Zamboni’s wife Elena was diagnosed with MS and he embarked on a mission to find out everything about it, from poring over medical literature dating back 100 years or more, to using state-of-the-art body-imaging techniques.

His conclusion was that this wasn’t only an autoimmune disease, but also a vascular one, caused by restricted, blocked, malformed or twisted veins in the trunk and neck. A small study showed that 90 per cent of his patients had venous obstruction. He named the condition chronic cerebrospinal venous insufficiency (CCSVI) and went further, postulating that an excess of iron, which causes inflammation and cell death, was responsible for tipping the immune system out of balance, resulting in MS symptoms.

The treatment was to unblock these twisted or malformed veins (similar to an angioplasty). What I found interesting is that an autoimmune disease, in this case MS, might not just be caused by the environment or genetic susceptibility, it might also include a physical malformation in the body that can be reversed! Might there be something similar with IBD? They should add that to the list of things to research.

UPDATE (8/2/2010): Saw an article in the WSJ about a study that refutes the Zamboni theory regarding jugular vein blockage. Jury is still out I suppose.

Why some people with IBD may not respond to corticosteroids

We all know that corticosteroids are one of the first drugs prescribed to deal with IBD. But it doesn't always work for everyone. Why?

I just came across a press release about new research that uncovered why many people with lupus (another autoimmune disease) do not respond to corticosteroids - or at least steroids in high doses. An excerpt that explains why this is the case:

Currently, those with lupus and other autoimmune diseases, commonly treat the condition with corticosteroids to suppress their overactive immune system and prevent it from attacking healthy tissues which can result in symptoms such as inflammation, pain and organ damage.

These steroid treatments work by killing certain immune system cells, including plasmacytoid dendritic cells (PDCs) that overproduce type 1 interferons, an immune system substance that contributes to lupus and other autoimmune diseases. However, unlike other conditions, steroid treatments are not as effective against these cells in those with lupus.

By largely studying children with systemic lupus erythematosus (SLE), BRI scientists in collaboration with scientists at Dynavax in Berkeley, CA, were able to solve the mystery behind the resistance. They determined that two immune system proteins known as toll-receptor 7 (TLR7) and toll-receptor 9 (TLR9), cause an activation of PDCs—the very cells steroids target—negating the effects of treatment. BRI scientists reported their findings in the June issue of the journal Nature.

A similar resistance mechanism might be at play with people with IBD (and other autoimmune diseases). It hasn't been proven yet obviously, but it's certainly something to consider when you're working with your doctor to deal with a serious flare-up. The traditional prednisone or budesonide (Entocort) may not work for you simply because your body works against the mechanism of the drugs.

Two new drugs that could be used for autoimmune and inflammatory diseases

Saw two recent articles about new drugs that could be used to treat autoimmune and inflammatory diseases, including multiple sclerosis, inflammatory bowel disease, arthritis, and others.

The first article was about a cancer drug, bortezomib, that was used in an animal study to treat inflammatory disease. The cancer drug induced cell death in only the harmful (active and proliferating) T-cells.

The second article was about a new protein from Compugen called CGEN-15001 that was found to abolish recurring relapses of multiple sclerosis in an animal study. The protein also delayed the onset of the disease. The protein apparently has some effect on the regulatory pathways in the immune system.

Both seem pretty interesting.

Virus Plus Gene Mutation Spurs Crohn's Disease in Mice

Saw an article about a new study that found a specific link between a gene mutation and virus that caused Crohn's Disease in mice. The study found that mice that had a gene variant linked to Crohn's Disease only developed Crohn's symptoms when they were infected by a specific, common norovirus called MNV.

Here's an excerpt:

Two years ago, the researchers at Washington University School of Medicine in St. Louis and others discovered that mice with an ATG16L1 gene variant associated with Crohn's disease in humans develop similar abnormalities in gut immune cells called Paneth cells. But the mutation alone wasn't enough to trigger Crohn's disease.

In a routine screening, the team later found that mice with the gene variant developed Crohn's disease symptoms within seven days after exposure to the MNV norovirus.

The study appears in the June 25 issue of the journal Cell.

It's been suspected that autoimmune and other diseases might be influenced by viral infections, but "this is the first really clear indication of a disease caused by a susceptibility gene and a specific virus," study co-leader Thaddeus Stappenback said in a journal news release.

That last statement is important. They found a specific viral infection that can trigger the disease for a specific genetic predisposition. Given there are many genetic markers for CD, there may be many possible viral infections (or bacterial infections) that can trigger the disease. So there is lots of research still to be done. But this is an important finding. As an aside, I had another recent post about a bacteria triggering arthritis in mice, so there are many angles on this research.

Nice overview of IBD, CD, and UC from Duke Research

Came across this nice 50 min overview video from Duke (my alma mater) covering different types of manifestations and management recommendations for inflammatory bowel disease, including both Crohn's Disease and Ulcerative Colitis. Highlights of note:

• minute 36:00 - The speaker comments on clinical protocol for inducing remission right around minute 36. Gives you an idea of what your doctor is basing their recommendations on.
• minute 39:30 - Non-Anti-TNF agents that are under clinical trial and study for treatment of IBD. Everything from helminthic therapy to stem cell treatment.

Broccoli extract effective against IBD and UC

Saw an article about how a plant-derived compound called Phenethylisothiocyanate (PEITC) showed potential anti-inflammatory activity and reversed many symptoms of ulcerative colitis. The PEITC compound is found naturally in the Brassica genus of plants, which includes cabbage, cauliflower, watercress, and broccoli.

An excerpt:

"I tested this substance in a mouse model that is already established and widely used. What we found is that it not only alleviates several clinical signs of ulcerative colitis — for example, it attenuates the damage that occurs in the colon tissues and colon epithelium, as well as the clinical signs like diarrhea and blood in stool. The weight loss is a major sign in colitis and that was alleviated, too," Dey added.

Good evidence to suggest that you should eat your greens! If you hate broccoli, you'll just have to get over it cause it's good for you.

Alopecia Areata and Narcolepsy both confirmed as autoimmune diseases

The list of health issues that are being categorized as autoimmune diseases are just stacking up! Saw an article a couple weeks ago that alopecia areata, a disease that causes hair loss and baldness, was caused by an autoimmune response. And a more recent article confirmed that narcolepsy is also autoimmune.

In alopecia areata, they found that some genes which attract killer immune cells are overexpressed in hair follicles. The immune cells attack the follicles and lead to rapid hair loss. In narcolepsy, the body's immune system attacks cells responsible for creating a certain hormone (hypocretin) in people's brains that's responsible for keeping people awake. The lack of hypocretin causes people to randomly and unexpectedly fall asleep.

It's amazing how many health problems are falling under the autoimmune category.