Abstract
We tested in a translational approach the usefulness of plasma creatine kinase (CK) as an objective biomarker for levodopa-induced dyskinesia (LID). Plasma CK levels were measured in five dyskinetic parkinsonian non-human primates (NHP) and in ten PD patients with LID who participated in a treatment trial with simvastatin. Plasma CK levels were increased in dyskinetic NHP and correlated with LID severity while they were not affected by LID severity in PD patients.
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References
Ahmed MR et al (2010) Lentiviral overexpression of GRK6 alleviates l-dopa-induced dyskinesia in experimental Parkinson’s disease. Sci Transl Med 2:28ra28. https://doi.org/10.1126/scitranslmed.3000664
Amanzio M, Palermo S, Zibetti M, Leotta D, Rosato R, Geminiani G, Lopiano L (2014) Self-unawareness of levodopa induced dyskinesias in patients with Parkinson’s disease. Brain Cogn 90:135–141. https://doi.org/10.1016/j.bandc.2014.06.014
Bastide MF et al (2015) Pathophysiology of l-dopa-induced motor and non-motor complications in Parkinson’s disease. Prog Neurobiol 132:96–168. https://doi.org/10.1016/j.pneurobio.2015.07.002
Bektas H, Deniz O, Temel S, Keklikoglu HD, Akyol S (2014) Rhabdomyolysis related to dyskinesia in Parkinson’s disease. J Mov Disord 7:25–27. https://doi.org/10.14802/jmd.14006
Berton O et al (2009) Striatal overexpression of DeltaJunD resets L-DOPA-induced dyskinesia in a primate model of Parkinson disease. Biol Psychiatry 66:554–561. https://doi.org/10.1016/j.biopsych.2009.04.005
Bezard E et al (2001) Relationship between the appearance of symptoms and the level of nigrostriatal degeneration in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaque model of Parkinson’s disease. J Neurosci 21:6853–6861
Bezard E et al (2003) Attenuation of levodopa-induced dyskinesia by normalizing dopamine D3 receptor function. Nat Med 9:762–767. https://doi.org/10.1038/nm875
Chapuis S, Ouchchane L, Metz O, Gerbaud L, Durif F (2005) Impact of the motor complications of Parkinson’s disease on the quality of life. Mov Disord 20:224–230. https://doi.org/10.1002/mds.20279
Chung KA, Lobb BM, Nutt JG, McNames J, Horak F (2010) Objective measurement of dyskinesia in Parkinson’s disease using a force plate. Mov Disord 25:602–608. https://doi.org/10.1002/mds.22856
Colosimo C et al (2010) Task force report on scales to assess dyskinesia in Parkinson’s disease: critique and recommendations. Mov Disord 25:1131–1142. https://doi.org/10.1002/mds.23072
Fasano S et al (2010) Inhibition of Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) signaling in the striatum reverts motor symptoms associated with L-dopa-induced dyskinesia. Proc Natl Acad Sci USA 107:21824–21829. https://doi.org/10.1073/pnas.1012071107
Fox SH, Johnston TH, Li Q, Brotchie J, Bezard E (2012) A critique of available scales and presentation of the non-human primate dyskinesia rating scale. Mov Disord 27:1373–1378. https://doi.org/10.1002/mds.25133
Hechtner MC et al (2014) Quality of life in Parkinson’s disease patients with motor fluctuations and dyskinesias in five European countries. Parkinsonism Relat Disord 20:969–974. https://doi.org/10.1016/j.parkreldis.2014.06.001
Khan FY (2009) Rhabdomyolysis: a review of the literature. Neth J Med 67:272–283
Koch AJ, Pereira R, Machado M (2014) The creatine kinase response to resistance exercise. J Musculoskelet Neuronal Interact 14:68–77
Lopane G, Mellone S, Chiari L, Cortelli P, Calandra-Buonaura G, Contin M (2015) Dyskinesia detection and monitoring by a single sensor in patients with Parkinson’s disease. Mov Disord 30:1267–1271. https://doi.org/10.1002/mds.26313
Lyoo CH, Lee MS (2011) Rhabdomyolysis induced by severe levodopa induced dyskinesia in a patient with Parkinson’s disease. J Neurol 258:1893–1894. https://doi.org/10.1007/s00415-011-6041-x
Machado M et al (2011) Effect of varying rest intervals between sets of assistance exercises on creatine kinase and lactate dehydrogenase responses. J Strength Cond Res 25:1339–1345. https://doi.org/10.1519/JSC.0b013e3181d680d6
Machado M, Willardson JM, Silva DR, Frigulha IC, Koch AJ, Souza SC (2012) Creatine kinase activity weakly correlates to volume completed following upper body resistance exercise. Res Q Exerc Sport 83:276–281. https://doi.org/10.1080/02701367.2012.10599858
Manson AJ, Brown P, O’Sullivan JD, Asselman P, Buckwell D, Lees AJ (2000) An ambulatory dyskinesia monitor. J Neurol Neurosurg Psychiatry 68:196–201. https://doi.org/10.1136/jnnp.68.2.196
Meissner WG et al (2011) Priorities in Parkinson’s disease research. Nat Rev Drug Discov 10:377–393. https://doi.org/10.1038/nrd3430
Mera TO, Burack MA, Giuffrida JP (2012a) Quantitative assessment of levodopa-induced dyskinesia using automated motion sensing technology. Conf Proc IEEE Eng Med Biol Soc 2012:154–157. https://doi.org/10.1109/EMBC.2012.6345894
Mera TO, Heldman DA, Espay AJ, Payne M, Giuffrida JP (2012b) Feasibility of home-based automated Parkinson’s disease motor assessment. J Neurosci Methods 203:152–156. https://doi.org/10.1016/j.jneumeth.2011.09.019
Noakes TD (1987) Effect of exercise on serum enzyme activities in humans. Sports Med 4:245–267
Pechevis M et al (2005) Effects of dyskinesias in Parkinson’s disease on quality of life and health-related costs: a prospective European study. Eur J Neurol 12:956–963. https://doi.org/10.1111/j.1468-1331.2005.01096.x
Perez-Lopez C et al (2016) Dopaminergic-induced dyskinesia assessment based on a single belt-worn accelerometer. Artif Intell Med 67:47–56. https://doi.org/10.1016/j.artmed.2016.01.001
Porras G et al (2012) PSD-95 expression controls L-DOPA dyskinesia through dopamine D1 receptor trafficking. J Clin Invest 122:3977–3989. https://doi.org/10.1172/jci59426
Shen W et al (2016) M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia. Neuron 90:1139. https://doi.org/10.1016/j.neuron.2016.05.017
Sherwood RA, Lambert A, Newham DJ, Wassif WS, Peters TJ (1996) The effect of eccentric exercise on serum creatine kinase activity in different ethnic groups. Ann Clin Biochem 33(Pt 4):324–329. https://doi.org/10.1177/000456329603300407
Singhal PC, Chugh KS, Gulati DR (1978) Myoglobinuria and renal failure after status epilepticus. Neurology 28:200–201
Termsarasab P, Frucht SJ (2017) Dystonic storm: a practical clinical and video review. J Clin Mov Disord 4:10. https://doi.org/10.1186/s40734-017-0057-z
Tison F et al (2013) Simvastatin decreases levodopa-induced dyskinesia in monkeys, but not in a randomized, placebo-controlled, multiple cross-over (“n-of-1”) exploratory trial of simvastatin against levodopa-induced dyskinesia in Parkinson’s disease patients. Parkinsonism Relat Disord 19:416–421. https://doi.org/10.1016/j.parkreldis.2012.12.003
Tsipouras MG, Tzallas AT, Rigas G, Tsouli S, Fotiadis DI, Konitsiotis S (2012) An automated methodology for levodopa-induced dyskinesia: assessment based on gyroscope and accelerometer signals. Artif Intell Med 55:127–135. https://doi.org/10.1016/j.artmed.2012.03.003
Tzallas AT et al (2014) PERFORM: a system for monitoring, assessment and management of patients with Parkinson’s disease. Sens (Basel) 14:21329–21357. https://doi.org/10.3390/s141121329
Urs NM et al (2015) Targeting beta-arrestin2 in the treatment of L-DOPA-induced dyskinesia in Parkinson’s disease. Proc Natl Acad Sci USA 112:E2517–2526. https://doi.org/10.1073/pnas.1502740112
Acknowledgements
The Simvastatin trial was funded by a Michael J. Fox Foundation Clinical Intervention Award 2008.
Funding
The Simvastatin trial was funded by a M. J. Fox Foundation Clinical Intervention Award 2008.
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None of the authors has a conflict of interest in relation to the research covered in the article. Outside the present study (past 12 months), QL and MG have nothing to declare. AD declares a grant from the Fondation pour la recherche médicale (FDM201806005951). FT has received a travel grant from ORKYN and research grants from the French Health Ministry (PHRC). EB has an equity stake in Motac holding Ltd and receives consultancy payments from Motac Neuroscience Ltd. Current grant support includes Agence Nationale de la Recherche, China Science Fund, Michael J Fox Foundation for Parkinson Research, France Parkinson, Fondation de France, Medical Research Council, Innovative Medicines Initiative (H2020, IMPRIND), IDEX Bordeaux, COEN, MSA Coalition, Rotary Foundation, Nouvelle-Aquitaine Regional Council, and LABEX Brain. OR has received grants from Agence Nationale de la Recherche (ANR), CHU de Toulouse, France-Parkinson, INSERM-DHOS Recherche Clinique Translationnelle, MJFox Foundation, Programme Hospitalier de Recherche Clinique, European Commission (FP7, H2020) and has served as scientific consultant for AbbVie, Adamas, Acorda, Addex, AlzProtect, Apopharma, Astra Zeneca, Bial, Biogen, Britannia, Clevexel, Cynapsus, INC Research, Lundbeck, Merck, MundiPharma, Neuroderm, Novartis, Oxford Biomedica, Parexel, Pfizer, Prexton Therapeutics, Quintiles, Sanofi, Servier, Teva, UCB, XenoPort, Zambon. EB has an equity stake in Motac holding Ltd and receives consultancy payments from Motac Neuroscience Ltd. Current grant support includes Agence Nationale de la Recherche, China Science Fund, Michael J Fox Foundation for Parkinson Research, France Parkinson, Fondation de France, Medical Research Council, Innovative Medicines Initiative (H2020, IMPRIND), IDEX Bordeaux, COEN, MSA Coalition, Rotary Foundation, Nouvelle-Aquitaine Regional Council, and LABEX Brain. WGM has received fees for editorial activities with Springer Nature, honoraria for consultancy activities from Sanofi, Lundbeck and Affiris, teaching honoraria from UCB, honoraria from MDS, as well as research support from the Michael J Fox Foundation, the University Hospital Bordeaux, the French Health Ministry, the European Community, ANR, ARAMISE, PSP-France, MSA Coalition, LABEX Excellence Initiative.
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All animal experiments were performed in accordance with the European Union directive of September 22, 2010 (2010/63/EU) on the protection of animals used for scientific purposes in an AAALAC-accredited facility following acceptance of study design by the Institute of Lab Animal Science (Chinese Academy of Science, Beijing, China).
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Written consent of all subjects of the simvastatin trial was obtained prior to enrolment and following ethics approval (CPP Sud-Ouest et Outremer 3).
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Delamarre, A., Tison, F., Li, Q. et al. Assessment of plasma creatine kinase as biomarker for levodopa-induced dyskinesia in Parkinson’s disease. J Neural Transm 126, 789–793 (2019). https://doi.org/10.1007/s00702-019-02015-x
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DOI: https://doi.org/10.1007/s00702-019-02015-x