Out of the Box Treatment for Multiple Sclerosis

I came across an article that is an interesting illustration of the scientific process in medicine that’s a good example of : 1. Good science reporting, 2. A well-reported Phase 1 clinical trial, 3. Good prior plausibility, and 4. Out of the box thinking.

There’s been some discussion of  bad science reporting when it comes to medicine. If something is lauded as a miracle-cure and it turns out not to be, then confidence in biomedical research is eroded. Sometimes real harm is done when people forgo evidence-based treatment in search of miracle “natural” cures. This is what is happening with stem-cell research, (too many miracles promised). I think stem cells are a good laboratory model for studying cell biology, possibly of certain diseases — but there’s little plausability that injecting stem cells into the body will cure everything from arthritis to Multiple Sclerosis.

Good Science Reporting

So I was pleasantly surprised when I read this article in Medical News Today. It’s an example of good science news reporting. First, they note that it’s a Phase 1 clinical trial, and what that means: assessing safety. There were no serious adverse events as a result of the therapy and the results of the trial didn’t cure the disease. The article gives a good lay-person description of Multiple Sclerosis. The author did not interview conspiracy cranks who might say that MS is caused by fluoride or chemtrails; just a frank & brief description of what is known about it. They give a description of how the therapy might work and why it might be better than current existing therapies. Then they summarize some of the findings: no one died, maintained immune function against tetanus (positive control marker). The article also unambiguously states that the study was too small to know if it was effective (editorial restraint!). Based on the sample size (9), we can’t know that the patients who were followed for 3 months didn’t progress with MS because they weren’t going to anyway, or as a result of the treatment. Only a large, double-blinded, controlled study comparing this therapy vs. another accepted therapy would work. The article mentions the next step — raising $1.5 mil. for Phase 2 trials. There is, of course, a positive and hopeful spin. But it does NOT over-state, it does NOT over-hype, it does NOT recommend the treatment for other indications, it does NOT conspiracy-monger, scientists are NOT “baffled,” and it does NOT give anecdotal testimony. My only critique is that they could have linked to the clinical trials registry (this is registered in the EU), and updated the article to link to the June 5 publication in Science Translational Medicine.

Out of the Box Thinking

I like this study because it explores a different avenue of therapy than those currently offered. The currently available MS therapy involves immunosuppression.

  1. Interferonβ therapy is a medication that is actually a protein secreted by human immune cells. Its major effects are to inhibit T cell proliferation and decrease interferon-γ production. It inhibits MHC class II expression — which is how immune & non-immune cells communicate with each other and facilitates the adaptive immune response (essentially saying “this thing is harmful”). It induces regulatory T-cell function, and inhibits monocyte activation — things that generally reduce the function of the immune system all over the body.
  2. Natalizumab is a monoclonal antibody that recognizes, binds to, and blocks a cell adhesion molecule (called α4-integrin). This adhesion molecule is on immune cells that allows them to attach to the lining of a tissue (e.g., blood vessel) and pass in between the cells to enter a specific body compartment (like the brain or intestines) and then carry out its immune functions. So essentially, your blocking your immune system from being able to monitor tissues distal from your blood, bone marrow, or lymph for infectious agents.
  3. Other immunosuppressive drugs like steroids (e.g., methylprednisolone) that cause generalized immunosupression and metabolic side-effects.

The treatment being described here takes another approach, and instead of being immune suppressive, it attempts to take advantage of the part of the immune system that recognizes “self” and induces immune-tolerance. There are built-in mechanisms of the normal functioning immune system to so suppress an immune reaction against our own proteins. This is something that happens during B-cell maturation in lymph nodes. If a B-cell recognizes “self” antigens too strongly, then it dies or undergoes apoptosis. What we want with MS, is for B-cells that might recognize myelin to die and not to produce antibodies & inflammation and destruction of myelin. The therapy described here is to take six known MS-related myelin antigens, tag them onto a patient’s leukocytes, undergo day-long quality-control tests, and inject them back into the patient. The leukocytes will then “train” the B cells that the myelin antigens are self, and hopefully undergo apoptosis. It’s a different take on the disease. It’s more specific than currently available therapy and it doesn’t induce immunosuppression.

It might not turn out to be effective, it might have serious adverse effects at higher dosages. It IS exciting because it is almost like a reverse-vaccine. Vaccines are used to induce an immune response to particular antigens (i.e.: on the tetanus bacteria), and this treatment is inducing immune tolerance to antigens (i.e.: human myelin). It isn’t being reported as a miracle cure, and it at has least an ounce of prior plausibility (unlike stem cell therapy). I’m looking forward to following the progress of line of research.

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