Helps exercise with dystonia

Dystonia - Research for Better Therapies

Dystonias (Greek: dysregulated tension) are movement disorders. The result: those affected suffer from involuntary convulsive movements and poor posture. The characteristics are very diverse. In severe cases, dystonia can affect the whole body. Often only one part of the body is affected, for example the hand. As with the composer Robert Schumann (1810–1856), who actually wanted to become a pianist. But dystonia ended his career and he turned to composing.

As different as they are - all forms of dystonia probably have a common cause: the regions of the brain that coordinate our unconscious movements work incorrectly. In terms of their cause, dystonias are therefore not purely muscular, but neurological disorders.

In the neurological clinic and polyclinic of the Würzburg University Hospital, private lecturer Dr. Chi Wang Ip Dystonia patients with botulinum toxin, also known as botox, among other things. Injected in the right dose, the nerve toxin produced by bacteria relaxes the muscles and reduces cramps. "Poison is always a question of the dose," says Ip. The effects of botulinum toxin can last for months. If it subsides, it is injected again. In this way, however, doctors can only alleviate the symptoms - a cure is not yet possible. In order to be able to treat patients more specifically in the future, senior physician Ip and his team are researching the causes and mechanisms of dystonia. The Federal Ministry of Education and Research promotes their work in the DYSTRACT network for the research and treatment of dystonic diseases.

Treating causes instead of just alleviating symptoms

“We are developing an animal model to get to the bottom of the possible causes of dystonia. In a second step, better therapies are to be developed on the basis of the new findings, ”said Ip. The focus of his work is the so-called idiopathic torsional dystonia, dystonia type 1 or DYT1 for short. It is considered the most common and most severe form of hereditary dystonias and is one of the rare diseases: one in 200,000 people is affected. Symptoms begin in childhood, usually in one arm or one leg. Often the children twist their hands and fingers in screw-like movement patterns. Most of the time, the dystonia spreads to other areas of the body. “People who develop dystonia are heavily stigmatized by society. That is why we want to improve the therapy options for children especially with DYT1, which starts early, ”says Ip.

Many dystonia patients reported in the Würzburg botulinum toxin and movement disorder clinic that they fell ill after a certain event, often after a physical trauma. For example, one patient reported that after an injury to the mouth while playing the trumpet, dystonia developed in the mouth area. “We know from DYT1 that only 30 to 40 percent of genetically predisposed people actually develop dystonia, even though they all have the same genetic change. Why do some get sick while others don't? We suspect that external influences are involved in triggering dystonia, ”explains Ip. The Würzburg researchers are testing this hypothesis on genetically modified mice. Their genetic modification affects the same gene that is also modified in DYT1 patients. It is the TOR1A gene, which encodes the blueprint of a protein. Its exact function is not yet known. However, researchers suspect that it helps to correctly fold and / or break down other proteins in the cell.

Interestingly, DYT1 mice do not develop dystonia - they usually do not show any symptoms of the disease. To test whether trauma could trigger the disease, the animals' sciatic nerve was depressed and its function impaired. In fact, Ip and his team succeeded for the first time in triggering a dystonia-like movement disorder in mice. They analyzed the animals' movements using a computer-assisted gait analysis and developed a scale for the severity of the dystonia.

"Research for Rare Diseases"

Since 2003, the Federal Ministry of Education and Research has been promoting networks that are dedicated to researching the causes and developing possible therapeutic approaches for specific rare diseases. This basic and therapeutic research is very important for patients and their families. This is why the Federal Ministry of Education and Research continues to pursue the “Research for Rare Diseases” funding line. The research associations, which were approved by the BMBF in 2016, work on specific disease groups such as B. dystonias, neuromuscular diseases or primary, so congenital immunodeficiencies. The alliances organize themselves in a speaker council to discuss overarching research questions and to present their results to a broader public. A coordination center supports them in this.

More information: www.research4rare.de

Can an outbreak of dystonia be prevented?

IP's team took a closer look at the dopamine metabolism in the brains of the mice. Dopamine is an important messenger substance in the nervous system. A transport protein stops its action by taking the released messenger substance back into the cells. This function could be disturbed in DYT1 patients. The defective DYT1 gene product may be responsible for this.

IP's working group found indications of a connection between the messenger substance and the development of dystonia. For example, DYT1 mice showed increased dopamine concentrations after triggering the dystonia. In addition, the severity of the dystonia could be modulated by changing the dopamine content in the brain of the mice. To do this, the mice received a precursor for the messenger substance, which is converted into dopamine in the brain. “These results give us valuable information for new treatment options. We may be able to prevent the onset of the disease in genetically predisposed children by counteracting elevated dopamine levels at an early stage, ”said Ip. The Würzburg team is currently working with scientists from Tübingen, Canada and the USA to find out more about the molecular changes in the brain that are related to the development of dystonia.

Rare Disease Day 2017 - a decade for the rare!

February 28, 2017 marks the tenth anniversary of Rare Diseases Day, this time under the motto: “Research helps heal!” In Germany alone, around four million people live with a rare disease; It is assumed that there are around 20 million people across Europe. Many of the underlying disease mechanisms are not yet understood, as around 80 percent of rare diseases are of genetic origin. Therefore, the cause research is sometimes very time-consuming and costly. Many actors have to be convinced that the commitment to rare diseases is “worthwhile”.

It is encouraging that more and more European countries are realizing that the need to help people with rare diseases is the order of the day. More and more cross-border projects are also being launched: especially in the case of diseases with a low number of cases, doctors and researchers are encouraged to network internationally and cooperate closely with one another. This is where the European research project E-Rare comes in: Scientists from 17 European countries are currently working together on research into rare diseases. The new initiative of the European Reference Networks also brings together clinics, doctors and researchers from Estonia to Portugal in order to jointly improve the care of patients with rare diseases and to better understand the underlying mechanisms of the diseases.

The next ten years should be used intensively to advance research and therapy development in the interests of patients throughout Germany and internationally.

More information: www.rarediseaseday.org

Contact Person:
Priv.-Doz. Dr. Chi Wang Ip and Prof. Dr. Jens Volkmann
Neurological Clinic and Polyclinic
of the university hospital
Josef-Schneider-Strasse 11
97080 Wuerzburg
0931 201-23775
0931 201-23697
[email protected]
[email protected]