@article{c0019d4e66e241a48a8ac4061ba8c533,
title = "Peripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylase",
abstract = "Peripheral decarboxylase inhibitors (PDIs) prevent conversion of levodopa to dopamine in the blood by the enzyme aromatic L-amino acid decarboxylase (AADC). Alterations in enzyme activity may contribute to the required higher dosages of levodopa observed in many patients with Parkinson{\textquoteright}s disease. We evaluated the effect of levodopa/PDI use on serum AADC enzyme activity. Serum AADC enzyme activity was evaluated in three independent cohorts of patients with Parkinson{\textquoteright}s disease or parkinsonism (n = 301) and compared between patients on levodopa/PDI vs. patients not on this medication. AADC enzyme activity was elevated in 62% of patients on levodopa/PDI treatment, compared to 19% of patients not on levodopa/PDI (median 90 mU/L vs. 50 mU/L, p < 0.001). Patients with elevated AADC activity had longer disease duration and higher doses of levodopa/PDI. These findings may implicate that peripheral AADC induction could underlie a waning effect of levodopa, necessitating dose increases to maintain a sustained therapeutic effect.",
author = "{van Rumund}, Anouke and Lukas Pavelka and Esselink, {Rianne A.J.} and Geurtz, {Ben P.M.} and Wevers, {Ron A.} and Brit Mollenhauer and Rejko Kr{\"u}ger and Bloem, {Bastiaan R.} and Verbeek, {Marcel M.}",
note = "Funding Information: The authors would like to thank all participants involved in the three cohort studies for their devotion in clinical data collection and processing. The authors would like to thank Colette Reniers, Duco Buma, and the employees of the Department of Laboratory Medicine in the Radboud University Medical Center for their work. The Radboudumc cohort was supported by a research grant from the Van Alkemade-Keuls Foundation, the Netherlands. The Kassel cohorts were supported by unrestricted research grants from the Paracelsus-Elena-Klinik, Kassel, Germany, and the Michael J. Fox Foundation for Parkinson{\textquoteright}s Research. The Luxembourg PD cohort was supported by grants from the Luxembourg National Research Fund (FNR) within the National Centre of Excellence in Research on Parkinson{\textquoteright}s disease (NCER-PD [FNR/ NCER13/BM/11264123]), the PEARL programme (FNR; FNR/P13/6682797 to RK), by the European Union{\textquoteright}s Horizon2020 research and innovation program under grant agreement no. 692320 (WIDESPREAD; CENTRE-PD; grant agreement no. 692320; CENTRE-PD to R.K.), by the European Union{\textquoteright}s EIT Health grant for MoveIT (ID: 18034), and by a MJFF grant (ID: 1480). The study sponsors had no influence on the study design, collection, and analysis of data, the writing of the paper, or the decision to submit the paper. Additionally, we acknowledge the joint effort of the NCER-PD consortium members generally contributing to the Luxembourg Parkinson{\textquoteright}s Study as listed below: Geeta Acharya, Gloria Aguayo, Myriam Alexandre, Dominic Allen, Wim Ammerlann, Maike Aurich, Federico Baldini, Rudi Balling, Peter Banda, Katy Beaumont, Regina Becker, Camille Bellora, Daniela Berg, Fay Betsou, Sylvia Binck, Alexandre Bisdorff, Dheeraj Bobbili, Kathrin Brockmann, Jessica Calmes, Lorieza Castillo, Nico Diederich, Rene Dondelinger, Daniela Esteves, Jean-Yves Ferrand, Ronan Fleming, Manon Gantenbein, Thomas Gasser, Piotr Gawron, Lars Geffers, Virginie Giarmana, Enrico Glaab, Clarissa PC Gomes, Nikolai Goncharenko, J{\'e}r{\^o}me Graas, Mariela Graziano, Valentin Groues, Anne Gr{\"u}newald, Wei Gu, Ga{\"e}l Hammot, Anne-Marie Hanff, Linda Hansen, Maxime Hansen, Hulda Haraldsd{\"o}ttir, Laurent Heirendt, Estelle Henry, Sylvia Herbrink, Johannes Hertel, Sascha Herzinger, Michael Heymann, Karsten Hiller, Geraldine Hipp, Michele Hu, Laetitia Huiart, Alexander Hundt, Nadine Jacoby, Jacek Jaros{\l}aw, Yohan Jaroz, Pierre Kolber, Rejko Kr{\"u}ger, Joachim Kutzera, Pauline Lambert, Zied Landoulsi, Catherine Larue, Roseline Lentz, Inga Liepelt, Robert Liszka, Laura Longhino, Victoria Lorentz, Paula Cristina Lupu, Clare Mackay, Walter Maetzler, Katrin Marcus, Guilherme Marques, Jan Martens, Piotr Matyjaszczyk, Patrick May, Francoise Meisch, Myriam Menster, Maura Minelli, Michel Mittelbronn, Brit Mollenhauer, Kathleen Mommaerts, Carlos Moreno, Friedrich M{\"u}hlschlegel, Romain Nati, Ulf Nehrbass, Sarah Nickels, Beatrice Nicolai, Jean-Paul Nicolay, Alberto Noronha, Wolfgang Oertel, Marek Ostaszewski, Sinthuja Pachchek, Claire Pauly, Lukas Pavelka, Magali Perquin, Dorothea Reiter, Isabel Rosety, Kirsten Rump, Estelle Sandt, Venkata Satagopam, Marc Schlesser, Margaux Schmitt, Sabine Schmitz, Susanne Schmitz, Reinhard Schneider, Jens Schwamborn, Alexandra Schweicher, Kate Sokolowska, Lara Stute, Ines Thiele, Cyrille Thinnes, Christophe Trefois, Jean-Pierre Trezzi, Johanna Trouet, Michel Vaillant, Daniel Vasco, Maharshi Vyas, Richard Wade-Martins, Paul Wilmes. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = mar,
day = "19",
doi = "10.1038/s41531-021-00172-z",
language = "English",
volume = "7",
pages = "29",
journal = "npj Parkinson's Disease",
issn = "2373-8057",
publisher = "Springer Nature",
number = "1",
}