Host: The 94th Annual Meeting of the Japanese Pharmacological Society
Name : The 94th Annual Meeting of the Japanese Pharmacological Society
Number : 94
Location : Sapporo
Date : March 08, 2021 - March 10, 2021
In this memorial lecture, I will review the long drug development history and belated US FDA approval of the adenosine A2A receptor (A2AR) antagonist istradefylline for treatment of Parkinson's disease (PD) and its implications. The A2AR has been long considered as the leading drug target for PD treatment for its highly concentrated expression in the striatopallidal neurons and its colocalization and functional antagonistic interact ion with dopamine D2 receptors in this neuron type. Since the early 1990s, mounting experimental findings have demonstrated the motor enhancement effect of A2AR antagonists, alone or synergizing with L-DOPA in rodents and non-human primates. Since 2001, more than 25 clinical trials were conducted to evaluate the safety and clinical efficacy of A2AR antagonists in PD patients. After more than two decades of preclinical and clinical studies, on August 27, 2019, the U.S. Food and Drug Administration (FDA) approved the adenosine A2A receptor antagonist Nourianz (istradefylline) developed by Kyowa Hakko-Kirin Inc., Japan, as an add-on treatment to levodopa in Parkinson's disease (PD) with "OFF" episodes. This milestone achievement represent is the first A2AR therapeutic drug and the first non-dopaminergic drug for PD treatment approved by US FDA in the last two decades. This approval provides an important lessons to be remembered, namely the selection of defined patients subpopulations who are most responsive to the tested drug is critical for a successful demonstration of the clinical efficacy of the drug. Importantly, this approval paves the way to foster entirely novel therapeutic opportunities for adenosine A2A receptor antagonists, such as neuroprotection or reversal of mood and cognitive deficits in PD and other neuropsychiatric diseases. As a pioneer, Professor Geoff Burnstock established the purinergic signaling field against all the odds more than 50 years ago and thus set up the stage for us to pursuit and achieve many milestone like this in near future.
