Thursday, July 30, 2009

Barking up the Wrong Tree...

barking up the wrong treeImage by iammikeb via Flickr

A promising experimental MS drug, targeted at patients with progressive disease, has failed its late stage trials. The drug, Dirucotide, was reported to have shown remarkable effectiveness in early-stage trials, and, as there are very limited treatment options for those with progressive MS, much anticipation accompanied the compound's hoped for success. To put it bluntly, the fact that this drug failed really sucks.

Dirucotide was designed to work by restoring a patient's immunological balance, thereby suppressing the immune attack that is supposedly behind the MS disease process. Its failure highlights two important points; first, that early stage trial results can be very misleading, and second, that perhaps it's time to look beyond tinkering with the immune system when searching for answers to the MS puzzle.

My neurologist has been warning me for years to take all published early-stage trial results with several grains of salt. More often than not, there are financial motivations behind their release; in the case of large public companies, to drive up stock prices, and in the case of smaller, private companies, to attract investor cash. One must never forget the power of the almighty dollar.

The unfortunate reality is that Multiple Sclerosis has become a multibillion dollar a year industry, and competition among competing drug manufacturers is intense. Stock prices rise and fall on bits of news and hints of future success or failure, and pharmaceutical companies provide a steady stream of positive information designed to pique investor interest. Dirucotide, for instance, was initially developed by a small biotech company, BioMS. After the drug's success in early trials, pharmaceutical giant Eli Lilly stepped in to partner with BioMS for the much larger late stage studies. Unfortunately, both companies were burned by the false optimism generated by the drug’s early positive results. This is not to say that those results were deliberately misleading, but they were put to very good use by the PR folks.

Virtually every MS drug on the market seeks to either modulate or suppress the immune system. According to the autoimmune theory that now dominates MS research, an aberrant immune response during which a patient's immune cells attack their own nerve tissue is the driving force behind the disease. Therefore, logic dictates that suppressing this immune attack should alleviate the ravages of the MS. One must simply get the body to stop disrespecting itself.

In patients with Relapsing Remitting Multiple Sclerosis, who exhibit high levels of inflammation in their central nervous systems, this approach has seen success, as is evidenced by reduced relapse rates and improved MRI images. In patients that eventually transition to or start out with progressive disease, in which there is typically very little evidence of inflammation, these therapeutic approaches have proven to have little or no value.

Left untreated, the vast majority of RRMS patients eventually transition to the progressive form of the disease. Even when treated, it's not clear that today's MS drugs do more than just delay this transition. Once a patient has transitioned to the progressive form of MS, drugs targeted at the immune system have proven to be virtually useless in arresting disability progression. Given that fact, it seems to me to that the immune response targeted by all current MS drugs is more a symptom of the disease than its cause.

In my mind, treating MS by suppressing the immune system is like treating a broken leg with painkillers. The patient stops hurting, but nothing is done to address the underlying cause of the pain. Of course, this analogy is a bit simplistic, as treating a broken leg with painkillers has no actual therapeutic value, whereas immunosuppression and modulation in RRMS patients has been shown to have more than cosmetic effect.

Still, the fact remains that there is some unknown factor driving the Multiple Sclerosis engine, a factor which continues to damage nerve tissue after the hallmark immune response subsides. Might it not be that the immune response seen in MS patients is not an attack directed at their own tissue at all, but is an overwrought and hyper-aggressive attempt by the body to respond to an as yet undiscovered "X factor"? Unfortunately, very little privately funded research is targeted at discovering what this hidden culprit might be.

Virtually every drug now being developed to treat MS is meant to either suppress or modulate the human immune system. Over 70% of medical research in the United States is funded by publicly traded pharmaceutical companies, whose legal mandate states that they are beholden to their stockholders, not to the patients taking their drugs. The job of a pharmaceutical company CEO is to increase his company's profits, and thus the price of its stock. Once again, it's all about the money, honey. When there are billions of dollars being made by marketing drugs that only marginally address the root cause of serious illnesses, the profit motive runs counter to the desire to find cures. To their credit, the drug companies have managed to develop products that have turned previously fatal diseases such as diabetes and AIDS into chronic illnesses, but this success has also served to make the victims of these diseases lifelong consumers of highly profitable pharmaceutical products.

I'll end with a plea to the MS researchers of the world: Please, please, stop focusing solely on the immune component of the Multiple Sclerosis disease process, and instead set your sights on whatever it is that might be destroying a patient's nervous system, or might be the root cause of a patient's immune system going on the attack.

Folks, it's time to start digging a little deeper...


  1. So . . . inflammatory conditions, such as migraine headaches, may actually have something to do with MS and the immunomodulation therapies?

  2. I hope your plea reaches the ears of at least some MS researchers, Marc!

    Of course their task is made so much more difficult by the fact that the course of this disease can be so different for different patients.

    I hope some answers are found, maybe not in our lifetime but sometime in the future...

  3. Someone is reasearching corrolation of brain eating with MS in Brazil. Hello! Who is funding this? Aren't there better things to do??

  4. BTW - I Never eat brains.

  5. I am very disappointed with the non-performance/ lies surrounding Dirucotide. I'm SPMS and out of medical options. I am Canadian and had a little bit of pride that this small company out of Alberta was making a contribution in the MS world. NOT.

    One less drug to suffer through I guess. I do hope the universe hears our pleas to find a cure. If it's too late to help me, please protect our children.

  6. I have my theories on the cause, though not being a scientist, no ideas on a cure. Sadly there is no prize for finding the cause. There is no money to be made there; only money lost as companies hide their discoveries in a race to be the first with a real treatment.