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The belated US FDA approval of the adenosine A2A receptor antagonist istradefylline for treatment of Parkinson’s disease

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Abstract

After more than two decades of preclinical and clinical studies, on August 27, 2019, the US 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 is the culmination of the decade-long clinical studies of the effects of istradefylline in more than 4000 PD patients. Istradefylline is the first non-dopaminergic drug approved by FDA for PD in the last two decades. This approval also provides some important lessons to be remembered, namely, concerning disease-specific adenosine signaling and targeting subpopulation of PD patients. 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.

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Funding

JFC is supported by National Natural Science Foundation of China grant (n° 96018002, n° 80217011, n° 80216083); start-up Fund from Wenzhou Medical University (n° 89212012); RAC is supported by Fundacion LaCaixa (HR17-00523), Centro 2020 (CENTRO-01-0145-FEDER-000008: BrainHealth 2020 and CENTRO-01-0246-FEDER-000010) and FCT (POCI-01-0145-FEDER-03127).

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  1. Molecular Neuropharmacology Laboratory, Wenzhou Medical University, Wenzhou, China

    Jiang-Fan Chen

  2. CNC-Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Rodrigo A. Cunha

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Correspondence to Jiang-Fan Chen.

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R.A. Cunha is a scientific consultant to ISIC – Institute for Scientific Information on Coffee.

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Chen, JF., Cunha, R.A. The belated US FDA approval of the adenosine A2A receptor antagonist istradefylline for treatment of Parkinson’s disease. Purinergic Signalling 16, 167–174 (2020). https://doi.org/10.1007/s11302-020-09694-2

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