Author:
Tänzler Dirk,Kipping Marc,Lederer Marcell,Günther Wiebke F.,Arlt Christian,Hüttelmaier Stefan,Merkenschlager Andreas,Sinz Andrea
Abstract
AbstractWe show the effects of the three purine derivatives, caffeine, theophylline, and istradefylline, on the cAMP production of 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 purines, 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, resulting in 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.
Publisher
Cold Spring Harbor Laboratory
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