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Generic Asthma Drug Emerges as Possible Treatment for ADCY5-Related Dyskinesia

March 8, 2023

Rare Daily Staff

The generic asthma drug theophylline has been show as a potential treatment for the movement disorder ADCY5-related dyskinesia, according to a recent study by Martin Luther University Halle-Wittenberg, University Medicine Halle, and University of Leipzig Medical Center.

In the journal PLOS ONE, the researchers describe the case of a child with ADCY5-related dyskinesia whose symptoms improved significantly with the drug.

ADCY5-related dyskinesia is an extremely rare disorder that causes dyskinesia and uncontrolled movements in affected individuals. It is caused by a mutation in the ADCY5 gene. It is characterized by involuntary movements, chorea, dystonia, athetosis, ballism, hypotonia, and sleep disruption. There is no cure for the condition and treatment protocols are still under discussion. It is often misdiagnosed as cerebral palsy, mitochondrial disease, epilepsy, and other movement disorders.

The genetic defect to the ADCY5 gene causes a specific enzyme in the cells to become overactive. This enzyme is involved in the production of the second messenger cAMP. In those affected by the condition, too much cAMP can lead to uncontrolled movements, dyskinesia, and many other symptoms, such as speech deficiencies, starting in early infancy.

The researchers said in the past, symptoms have been treated with muscle relaxants, but these have severe side effects. By chance, a case came to light, in which a family in the United States treated their child with coffee to alleviate the symptoms. In a small study of 30 children, almost all benefited from caffeine treatment.

“Caffeine reduces the uncontrolled movements. The treatment also has drawbacks and the children often have trouble sleeping,” said Andrea Sinz, a professor at the Institute of Pharmacy at MLU.

The researchers from Halle and Leipzig looked for existing drugs resembling the structure of caffeine. The thought was that such drugs might work even better and have fewer side effects than caffeine.

The researchers found what they were looking for in the asthma drug theophylline and the Parkinson drug istradefylline. Istradefylline is not an approved drug in Europe. Cell experiments were conducted together at the Institute of Molecular Medicine at University Medicine Halle. The experiments showed that in ADCY5-related dyskinesia, the drugs reduced the production of the intracellular second messenger cAMP in the cells.

The researchers administered theophylline to a child suffering from ADCY5-related dyskinesia at the University of Leipzig Medical Center. The drug is approved for use in children. Researchers administered the drug in low doses and gradually increased it while closely monitoring the child.

“The results were phenomenal: the child straightened up, the dyskinesia and uncontrolled movements decreased, and even disappeared completely during sleep,” said Sinz.

After a few months, the child was able to get out of a wheelchair, walk, and speak more clearly. At the same time, no side effects were observed.

“Theophylline was able to alleviate symptoms in a controlled manner and increase the child’s quality of life in an impressive way. Our work is initially only a case study, but it already provides new hope for families affected around the world,” said Sinz. “Larger studies with more children across the globe started recently, and all of them are showing early success, especially in walking and talking. We hope that the results will lead to a regular therapy as soon as possible.”

Photo: Andrea Sinz, a professor at the Institute of Pharmacy at Martin Luther University Halle-Wittenberg

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