RESEARCH
Where Is It At?

The Dystonia Foundation holds regular medical conferences where dystonia experts from all over the world discuss advances in research. It is encouraging to see that this work has now given rise to increased interest in dystonia among researchers. Earlier this year, for example, the U.S. government announced a new program to support scientists who wish to study "the causes and mechanisms of dystonia." 

At a symposium held in Atlanta this summer, it was reported that "dramatic progress" is being made in dystonia research. Here are some of the advances made in recent years.

Dopa-Responsive Dystonia

Thanks to genetic research, in 1995 it was discovered that a rare form of dystonia called dopa-responsive could be practically cured with a drug called levodopa. It was discovered that with this form of dystonia a gene deficiency leads to a lowered production of a chemical called dopamine that plays a crucial role as a message transmitter in the brain. The problem can be corrected by raising the level of dopamine with small doses of levodopa. The two children that appeared on Oprah Winfrey's "It's A Miracle" earlier this month have dopa-responsibe dystonia. It is the only form of dystonia that benefits from medication so remarkably. When the discovery was made, doctors began giving levodopa to patients with other forms of dystonia, but without success.

Hereditary Dystonias

Recently scientists have traced the defective gene in a form of generalized dystonia to abnormalities in a gene they have called DYT1. Only about 30% of carriers of the gene develop symptoms. If a person carries the gene but still has no symptoms by the age of 28, he or she may live the rest of their lives without symptoms.

The DYT1 gene is the code for a protein called TorsinA whose exact function is still unknown. Scientists speculate that it is also associated with an imbalance in dopamine signalling in the brain. Whatever it does, it is clear that it interferes with the developmental process of the brain. Researchers are looking into this.

Here in Ottawa Dr. David Grimes is researching another form of inherited dystonia called inherited myoclonus-dystonia (IMD). Dr. Grimes explains: "It is a rare form of dystonia that normally begins in childhood. Individuals affected often have both dystonia and another involuntary movement called myoclonus. Myoclonus is a rapid jerking movement that can affect any muscle in the body. The basic understanding of this form of dystonia is just beginning to be unravelled as two different genes have now been implicated in its cause. The first gene is called the D2 dopamine receptor gene found on chromosome 11. However it is not clear at this point whether this gene can cause the disease on it's own or not. The second gene called epsilon sarcoglycan is found on chromosome 7 and is involved in supporting the cells' outer covering. It seems at this point that in many individuals with IMD, their dystonia is caused by abnormalities in this gene."

This discovery has prompted a whole new thinking on how this particular form of dystonia could be caused, says Dr. Grimes. Recently IMD has also been linked in one family to a area on chromosome 18. A specific gene defect has not been found yet but other cell covering genes that are found in this area on chromosome 18 are currently being investigated for abnormalities. "Understanding how rare sub types of dystonia are caused will improve our understanding of the more common forms of dystonia," says Dr. Grimes.

Problems with Sensory Process

Many people with dystonia know from experience that sometimes they can prevent an abnormal movement by moving in a particular way, by lifting their arms, touching their face, singing out loud, holding a straw protruding from their mouth, etc. These are called "sensory tricks" (geste antagoniste) and scientists have been investigating this phenomenon. They discovered that there is a sensory deficit in dystonia and the "sensory tricks" may be an instinctive attempt to correct it.

Dystonic movements are characterized by simultaneous contraction of muscles that move the body in opposite directions. In properly executing a movement the muscle to be activated must be excited while the opposite muscle and other nearby muscles must be inhibited. Research now believes that there is a loss of inhibition in dystonia. The pathway to the central brain that is responsible for exciting the muscles is working fine but the pathway responsible for inhibiting the opposite muscles is not. The "sensory tricks" might play the role of causing the required inhibition. Researchers are presently investigating this using different approaches like drugs or "brain retraining" exercises.

Treatment

The introduction of botulinum toxin in the late 1980's revolutionized the treatment of dystonia. Botox has become the most used therapeutic tool in the treatment of blepharospasm, oromandibular dystonia, spasmodic dysphonia, cervical dystonia, and writers cramp and other limb dystonias. But it does not work for everyone.

Various drugs are used to treat dystonia with relative success, but there is no consistency and often patients choose to do without the side effects. Scientists recognize that the treatment of dystonia with drugs is largely based on empirical rather than scientific rationale. In other words, if a particular drug works for you, keep using it, but there is no explanation for why it works. Drugs called "anticholinergics" have been found to be most useful in the treatment of generalized and segmental dystonia. Other drugs that are sometimes useful are the benzodiazepines, baclofen, and anticonvulsants such as carbamazepine. Of course you may know them as Ativan, Clonazepam, Lorazepam, etc.

The real progress in terms of drugs is that patients, talking with their doctors, learn as they go about dosage and when to take it. 

Most importantly, it has become clear that patient education, physical therapy, complementary therapies, healthy living and supportive care are very important integral elements of a comprehensive treatment of dystonia.