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OHSU researchers produce first animal model for stress-induced movement disorder


Research helps physicians understand rare form of ataxia that causes patients to appear ’drunk’ at times

Scientists at Oregon Health & Science University are the first to produce an animal model for episodic ataxia. The condition causes patients to suffer bouts of extreme clumsiness where they have balance, speech and motor difficulties. The research helps scientists better understand this rare and intriguing disorder. It may also help provide valuable information for improved, targeted drugs for treatment. The research is printed in the April edition of the journal Nature Neuroscience. It was conducted in conjunction with researchers at the Portland Veterans Affairs Medical Center.

"By developing a mouse model for episodic ataxia, we now have a valuable tool to better understand and treat the disease," said James Maylie, Ph.D., a professor of obstetrics and gynecology in the OHSU School of Medicine. "We have already used this animal model to observe and learn more about cellular mechanisms behind the disease. These disease-linked cells are located in the cerebellum, a portion of the brain involved in motor coordination."

The research also helps explain how a medication commonly used to treat patients works. "Acetazolamide is often given to patients with episodic ataxia," Maylie said. "Using these mice models, we were able to establish how acetazolamide acts at a cellular level to combat the disorder, something that was previously unknown."

Approximately 150,000 Americans are affected by the various forms of ataxia. The disorder is characterized by poor motor coordination. Specifically, it can cause hand coordination problems, poor balance and slurred speech. People with ataxia are often accused of acting drunk. In most ataxia disorders, the coordination problems are present all the time. In episodic ataxia, the coordination problems come on suddenly, often in stressful situations, and last for minutes or hours.

"Episodic ataxia is one form of the condition involving intermittent spells where sufferers simply can’t control their limbs," said John Nutt, M.D., director of the Parkinson Center of Oregon, which also treats patients with ataxia. "These attacks can last anywhere from a couple of minutes to three or four hours, and they are often triggered by stress, exercise or vigorous activity. In between episodes, patients are completely normal. Episodic ataxia is frequently caused by genetic mutations, but in some cases, multiple sclerosis can be the cause."

Years ago Nutt and his colleagues helped define clinical features of what they thought were three different types of inherited episodic ataxia while working with families seen in the OHSU neurogenetics clinic. In 1994 OHSU researchers Michael Litt, Ph.D., professor of molecular and medical genetics in the OHSU School of Medicine, and research associate David Browne, Ph.D., determined that the disease was caused in some families by a mutation in a gene that controls the flow of potassium in and out of nerve cells. This was the first human disease linked to the malfunction of a potassium gene. Testing all the families with this disorder in the neurogenetics clinic proved that two genes, and not three genes as the clinicians had thought, were responsible for the episodic ataxias. Subsequently other investigators found that a second variant of episodic ataxia was caused by a mutation in a gene that controlled the flow of calcium through the cell membrane.

This research was funded by the National Institute of Neurological Disorders and Stroke, a component of the National Institutes of Health, and the National Ataxia Foundation.

Jim Newman | EurekAlert!
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