Pursuing New Treatments for Cervical Dystonia

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Erwin B. Montgomery, Jr. MD
University of Alabama
1720 7th Ave. South Ste. 350C
Birmingham, AL 35294
January 19, 2009

While there are effective treatments for cervical dystonia such as botulinum toxin injections or Deep Brain Stimulation, many patients have only incomplete relief. Consequently, there is a need for better treatments. But how are we to find these better treatments? Unfortunately, Mother Nature has not given us many clues. In Parkinson’s disease, there is a specific abnormality that can be seen in the brains of patients, specifically, degeneration of the dopamine neurons. Discovery of the loss of dopamine neurons lead to a rational development of medications that attempt to replace the actions of the lost dopamine.

Even with today’s technology, the brains of patients with cervical dystonia appear normal. We cannot trace the cause of dystonia to abnormalities in any one part of the brain, any one type of nerve cell or one type of brain chemical. So where do we look for clues that will help?

For generalized dystonia, important clues for possible future therapies are gained from important research in the genetic causes of some forms of dystonia. But there are problems with this approach. First, while it is possible that understanding the causes of some forms of generalized dystonia may help future patients with cervical dystonia, there is no guarantee that this will happen. Even if a genetic basis for cervical dystonia were discovered it is probably many years, if not decades, before such discoveries lead to better treatments. Even if there is a genetic basis for cervical dystonia, the damage done by the genetic abnormality may not be reversible. This is particularly true if the genetic abnormality causes a cascade of secondary problems in the brain. Consequently, we need to look elsewhere if we are to better help patients here and now. We need to know how brain activity is abnormal whatever the cause and then find ways to restore normal brain activity. It is not clear that first finding the gene will translate to understanding how brain activity becomes abnormal.

There is reason for optimism. There are effective therapies that may get at the direct mechanisms by which neurons in the brain cause cervical dystonia. Botulinum toxin injections, while very effective, only mask the symptoms by preventing the abnormal brain activity from causing the muscles in the head and neck to contract. Deep Brain Stimulation does not prevent the muscles from contracting and may work by directly affecting the abnormal brain activity in patients with cervical dystonia.

One of our research projects examines how neural activity in the brains of patients with cervical dystonia is abnormal. Once we know how neuronal activity is abnormal we can look for ways to reproduce those abnormalities in the brains of laboratory animals to create what is called an “animal model” for cervical dystonia. Such animal models are extremely important. For example, the incredible explosion of research in new treatments for Parkinson’s disease was a direct result of the discovery of a chemical toxin that reliably reproduces in laboratory animals many of the brain abnormalities seen in humans with Parkinson’s disease. This allowed for a dramatic increase in research in Parkinson’s disease and many new therapies. We hope to do the same for cervical dystonia.

How are we going to determine what the brain abnormalities are in patients with cervical dystonia? During DBS, we routinely record the electrical activity of individual nerve cells in specific parts of the brain such as the globus pallidus which is within the basal ganglia of the brain and important in whatever causes cervical dystonia. Before placing the permanent DBS electrodes, we use a temporary microelectrode. The tip of the electrode is very small, about the size of three red blood cells placed next to each other. This small tip allows us to record electrical activities from individual nerve cells in the brain. Nerve cells in the globus palllidus communicate and instruct other neurons and muscles using pulses of electricity that can be recorded. The problem is analyzing what the neurons are saying to each other and how that communication fails and causes dystonia.

A big problem is how to know what neuronal activity is normal and what activity is abnormal. Obviously, we cannot record neuronal activity in normal persons. We need to compare the neuronal activities in the part of the brain affected by dystonia to parts of the brain not affected by dystonia, such as the same part of the brain in patients with other neurological conditions. But this problematic because you are not comparing the neuronal activity in parts of the brain affected by dystonia to normal brains.

We are trying to get around this problem by taking advantage of the relatively restricted effects of cervical dystonia. We plan to record in areas of the brain related to muscles that are involved such as the head and neck and areas in the brain not affected by the dystonia, such as arm or a leg. We then will compare the neuronal activities between these different areas to determine what id abnormal. We then can attempt to reproduce these abnormalities in laboratory animals and this may lead to better treatments as well.

There are many challenges facing our research. It is expensive and we are dependant on external funding through grants and gifts. We are very appreciative of the grants we have received from Spasmodic Torticollis/Dystonia, Inc. Also scientists are under constant threats by animal rights terrorists. Studying the genetics and molecular changes that occur in dystonia may lead to preventions or possible cures many years in the future and this is very attractive to scientists, foundations and institutes. While it seems that these projects get a much greater share of support, we are motivated to this being our line of research because we believe it will help patients sooner.

My mom and I wanted to thank you for hosting such a great symposium this year. This was our third year and we are looking forward to next years. E. Mathews