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Effects of theophylline on ADCY5 activation—From cellular studies to improved therapeutic options for ADCY5-related dyskinesia patients

by Tänzler, Dirk , Arlt, Christian , Lederer, Marcell , Günther, Wiebke F. , Hüttelmaier, Stefan , Sinz, Andrea , Kipping, Marc , Merkenschlager, Andreas

in Adenosine triphosphate / Adenylate cyclase / Amino acids / Biology and Life Sciences / Bronchodilator Agents / Caffeine / Care and treatment / Catalytic activity / Cell lines / Child, Preschool / Comparative analysis / Cyclic adenylic acid / Cyclic AMP / Diuretics / Dyskinesia / Dyskinesias / Enzymes / Health aspects / Humans / Instrument industry / Medical research / Medicine and Health Sciences / Medicine, Experimental / Movement disorders / Mutants / Mutation / Patient outcomes / Phosphodiesterase Inhibitors / Physical Sciences / Psychomotor Agitation / Signs and symptoms / Theophylline / Vasodilator Agents

2023

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Effects of theophylline on ADCY5 activation—From cellular studies to improved therapeutic options for ADCY5-related dyskinesia patients

by Tänzler, Dirk , Arlt, Christian , Lederer, Marcell , Günther, Wiebke F. , Hüttelmaier, Stefan , Sinz, Andrea , Kipping, Marc , Merkenschlager, Andreas

2023

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Effects of theophylline on ADCY5 activation—From cellular studies to improved therapeutic options for ADCY5-related dyskinesia patients

by Tänzler, Dirk , Arlt, Christian , Lederer, Marcell , Günther, Wiebke F. , Hüttelmaier, Stefan , Sinz, Andrea , Kipping, Marc , Merkenschlager, Andreas

2023

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Journal Article

Effects of theophylline on ADCY5 activation—From cellular studies to improved therapeutic options for ADCY5-related dyskinesia patients

Tänzler, Dirk,

Arlt, Christian,

Lederer, Marcell,

Günther, Wiebke F.,

Hüttelmaier, Stefan,

Sinz, Andrea,

Kipping, Marc,

Merkenschlager, Andreas

2023

Overview

We show the effects of the three purine derivatives, caffeine, theophylline, and istradefylline, on cAMP production by adenylyl cyclase 5 (ADCY5)-overexpressing cell lines. A comparison of cAMP levels was performed for ADCY5 wild-type and R418W mutant cells. ADCY5-catalyzed cAMP production was reduced with all three purine derivatives, while the most pronounced effects on cAMP reduction were observed for ADCY5 R418W mutant cells. The gain-of-function ADCY5 R418W mutant is characterized by an increased catalytic activity resulting in elevated cAMP levels that cause kinetic disorders or dyskinesia in patients. Based on our findings in ADCY5 cells, a slow-release formulation of theophylline was administered to a preschool-aged patient with ADCY5-related dyskinesia. A striking improvement of symptoms was observed, outperforming the effects of caffeine that had previously been administered to the same patient. We suggest considering theophylline as an alternative therapeutic option to treat ADCY5-related dyskinesia in patients.

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Publisher

Public Library of Science,Public Library of Science (PLoS)

Subject

Adenosine triphosphate

/ Adenylate cyclase

/ Amino acids

/ Biology and Life Sciences

/ Bronchodilator Agents

/ Caffeine

/ Care and treatment