DMRF-funded Investigators Clarify Important Aspects of Dystonia Disease Process

Advancements in dystonia research continue to unfold. Two separate teams of investigators have recently published important discoveries that are providing new insights into the origins and cause of the disorder.

Effects of Dystonia Alleviated by Common Medication in Novel Mouse Model
Developing animal models of dystonia that replicate at least some of the major symptoms of the disease remains a big challenge. One of the best strategies is generation of transgenic animals that carry  human genes, such as the  human DYT1 gene that carries the dystonia-causing mutation. Dr. Yuqing Li, University of Florida, and his collaborators developed such mouse models and tested them for a variety of motor deficits and neurophysiological deficiencies. In a new study, partially supported by the DMRF, they report that a commonly used drug to treat dystonia reverses such deficits proving that the mouse model can serve as a valid tool to test future drugs and further dissect the disease mechanisms. Trihexyphenidyl, known to many dystonia patients, restored not only motor deficits of these animals but alleviated the neurophysiological effects of the mutation, measured in isolated brain slices. The study also implicates the involvement of specific dopamine receptors and calcium channels in producing dystonic impairments. Overall, communication between striatal neurons and synaptic plasticity appears to be responsible for the movement abnormalities in these DYT1 animal models.

New Gene Discovered for Paroxysmal Dyskinesias
An international team of researchers that involved geneticists and neurologists from far corners of the globe, led by past DMRF grant recipient and Medical & Scientific Advisory Council Member Dr. Louis Ptacek at the University of California, San Francisco, has identified the gene responsible for paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC), a cause of epilepsy in infants and movement disorders in children. More than 100 families participated in the study by donating their DNA and undergoing genetic testing.

The origins of the disorder lie in a mysterious gene called PRRT2. Nobody knows what this gene does, and it bears little resemblance to other genes in the human genome. Discovering the gene that causes PKD/IC will allow researchers to study the disease mechanism and will provide doctors the opportunity to improve diagnosis through precise genetic testing. The work may also shed light on other c movement disorders, including the dystonias. This research was partially funded by the DMRF.

Neurology Now published a summary of Dr. Ptacek's work January 19, 2012.

12/21/11

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