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Treatment for PPMS

Posted Sep 29 2009 10:33pm


Our brains continuously repair themselves, no differently than other organ systems. We have a number of defense mechanisms built in to protect those systems. For example, our skin is the first barrier to pathogens. We have an immune system to fight off intruders if they get by the skin. Mucosal layers inside our bodies are also defenders, as are the hair in our noses or our eyelashes. The skin cells, hair, and mucous die off, are shed, and grow back. We have different levels of defense built in to our body; redundant systems, you might say. If one system doesn't work, the next line of defense kicks in, and so on.

Myelin is one of the defense mechanisms built in to protect the central nervous system (and you thought it was just a way to transmit signals more efficiently). When myelin is destroyed, it can and usually does, grow back. The process of demyelination and remyelination is the basis of relapsing remitting multiple sclerosis. But you already knew that. Repeated demyelination leads to fewer successful remyelinations.

The blood brain barrier is another one of the body's defence mechanism. It normally prevents pathogens and T cells(immune cells) from entering the CNS. But an infection or virus can compromise its ability. When the body recovers from the infection, the blood brain barrier can regain its integrity and the pathogens or T cells are trapped on the wrong side where they can wreak their havoc. The T cells detect myelin as foreign matter and set out to destroy it. That triggers the inflammatory process which stimulates other immune cells which causes more inflammation which stimulates other immune cells...and so on.

Demyelination is what causes the signals to be transmitted improperly or not at all. It leaves the neuron exposed to pathogens or danger and leaves it vulnerable to destruction. This is what causes permanent disability. In the relapsing remitting form of MS, demyelination results in an inflammatory reaction. In the primary progressive form of MS there is no remyelination and very little inflammation, so the neurons are left unprotected. The current drugs on the market and those in the pipeline focus on the inflammatory process by attempting to reduce it. And that's the basic reason we have little in the way of a treatment for PPMS.

From the National Multiple Sclerosis Society website:
" * The immune-modulating drugs currently used to treat relapsing forms of MS do not seem to be as effective in PPMS.
* In PPMS, there is a lack of easily-identifiable outcomes to measure in clinical trials. In the trials for the approved disease-modifying therapies (the interferon beta medications, glatiramer acetate, natalizumab, and mitoxantrone) investigators looked at outcomes such as number of relapses and number of new lesions (also called plaques) seen on magnetic resonance imaging (MRI) to determine if people who received the treatment had lower numbers than those who received a placebo (non-active substance). In other words, the investigators looked at things they could easily count over the course of a two-three year trial. Because people with PPMS don’t experience relapses or the same kind of inflammation in the central nervous system, there are fewer events that can be counted.
* The disease progression that occurs in PPMS can be quite slow — which means that a trial would have to last many years to determine if a treatment slowed or halted that progression."

There are a few drug trials going on for treatment of PPMS, but the main focus surrounds repair and protection. By the time a person is diagnosed with PPMS, the damage has already been done. So how do we stop MS at this stage and how do we repair the damage? The best treatment for PPMS at this point would appear to be autologous stem cell transplant.

I've written about Autologous Stem Cell Transplant before, but here's a recap:
First, bone marrow is removed from the MS patient. The patient then undergoes chemotherapy to completely anhilate their own immune system. Then transplant the bone marrow back into the patient. In essence, the patient's immune system is shut off, then turned back on again, much like rebooting a computer. There is a current study under way in Ottawa, lead by Dr. Mark Freedman. His purpose in beginning that study was to observe the genesis of MS. So far the study is a failure as no one has shown any signs or symptoms of MS since being transplanted. By rebooting the immune system, MS was destroyed. Cool. But this is still a study that is going on and will for some time. And the cost is quite high.

After we've stopped the disease in its track, then repair of the damage has to begin. There are a number of researchers looking at improving the repair process, but these are still in the animal studies stage. Researchers are also investigating methods of repairing the blood brain barrier to promote myelin repair.

What can we do now to promote the repair process? Eat fat. Well, that's a little simplistic, but myelin really is fatty tissue so eat foods with the healthy fats in them. From Wikipedia:
"The Canadian Government has recognized the importance of DHA omega-3 and permits the following biological role claim for DHA: 'DHA, an omega-3 fatty acid, supports the normal development of the brain, eyes and nerves'....As the importance of omega-3 fatty acids to health has received increasing awareness, the number of food products enriched in omega-3 fatty acids has increased. Many companies add fish oil or flax oil into their final product to enrich it in omega-3 fatty acids. Some animal products, such as milk and eggs, can be naturally enriched for omega-3 fatty acids by feeding the animals a diet that is rich in omega-3 fatty acids."

There are few studies of chemotherapy and rituximab on PPMS patients but for the reasons noted above, it will be a while before results, if any, are seen. In the meantime, keep shouting from the rooftops for people to donate money for the MS cause. In my most recent presentations to community groups about why donating to MS is a good idea, I stress the need for support of people with disabling MS. I stress that if I have to, I can take a needle once a week for the rest of my life if necessary, but I don't want to watch my friends and colleagues becoming bedridden.

S.
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