A Clinical Trial of Isradipine: What Went Wrong?
Authors: Baijayanta Maiti, Joel S. Perlmutter
Journal: Annals of Internal Medicine (2020)

Editorials5 May 2020A Clinical Trial of Isradipine: What Went Wrong?Baijayanta Maiti, MD, PhD and Joel S. Perlmutter, MDBaijayanta Maiti, MD, PhDWashington University School of Medicine, St. Louis, Missouri (B.M., J.S.P.)Search for more papers by this author and Joel S. Perlmutter, MDWashington University School of Medicine, St. Louis, Missouri (B.M., J.S.P.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-1023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Parkinson disease (PD) is the second most common progressive neurodegenerative disorder, marked by the relentless progression of a mélange of motor and nonmotor symptoms. Treatment with levodopa or related medications provides substantial relief for most motor symptoms, especially early in the disease, whereas treatment for most nonmotor symptoms remains utterly inadequate. Moreover, no current agents stall or even delay PD progression. The projected increase in PD prevalence (1), with the daunting socioeconomic burden that accompanies it, pushes investigators and the public to develop a disease-modifying therapy. Industry and the federal government have supported clinical investigators in testing many drugs during ...References1. Dorsey ER, Constantinescu R, Thompson JP, et al. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology. 2007;68:384-6. [PMID: 17082464] CrossrefMedlineGoogle Scholar2. The Parkinson Study Group STEADY-PD III Investigators. Isradipine versus placebo in early Parkinson disease. A randomized trial. Ann Intern Med. 2020;172:591-8. doi:10.7326/M19-2534 LinkGoogle Scholar3. Surmeier DJ, Guzman JN, Sanchez J, et al. Physiological phenotype and vulnerability in Parkinson's disease. Cold Spring Harb Perspect Med. 2012;2:a009290. [PMID: 22762023] doi:10.1101/cshperspect.a009290 CrossrefMedlineGoogle Scholar4. Ilijic E, Guzman JN, Surmeier DJ. The L-type channel antagonist isradipine is neuroprotective in a mouse model of Parkinson's disease. Neurobiol Dis. 2011;43:364-71. [PMID: 21515375] doi:10.1016/j.nbd.2011.04.007 CrossrefMedlineGoogle Scholar5. Ritz B, Rhodes SL, Qian L, et al. L-type calcium channel blockers and Parkinson disease in Denmark. Ann Neurol. 2010;67:600-6. [PMID: 20437557] doi:10.1002/ana.21937 CrossrefMedlineGoogle Scholar6. Braak H, Ghebremedhin E, Rüb U, et al. Stages in the development of Parkinson's disease-related pathology. Cell Tissue Res. 2004;318:121-34. [PMID: 15338272] CrossrefMedlineGoogle Scholar7. Kordower JH, Olanow CW, Dodiya HB, et al. Disease duration and the integrity of the nigrostriatal system in Parkinson's disease. Brain. 2013;136:2419-31. [PMID: 23884810] doi:10.1093/brain/awt192 CrossrefMedlineGoogle Scholar8. Nandhagopal R, Kuramoto L, Schulzer M, et al. Longitudinal evolution of compensatory changes in striatal dopamine processing in Parkinson's disease. Brain. 2011;134:3290-8. [PMID: 22075521] doi:10.1093/brain/awr233 CrossrefMedlineGoogle Scholar9. Karimi M, Tian L, Brown CA, et al. Validation of nigrostriatal positron emission tomographic measures: critical limits. Ann Neurol. 2013;73:390-396. [PMID: 23423933] doi:10.1002/ana.23798 CrossrefMedlineGoogle Scholar10. Brown CA, Karimi MK, Tian L, et al. Validation of midbrain positron emission tomography measures for nigrostriatal neurons in macaques. Ann Neurol. 2013;74:602-10. [PMID: 23686841] doi:10.1002/ana.23939 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Washington University School of Medicine, St. Louis, Missouri (B.M., J.S.P.)Grant Support: By grants NS075321, NS103957, NS107281, U19 NS110456, and KL2 TR002346 from the National Institutes of Health, National Institute of Neurological Disorders and Stroke, and National Institute on Aging; National Center for Advancing Translational Sciences of the National Institutes of Health; American Parkinson Disease Association Advanced Research Center at Washington University; Greater St. Louis Chapter of the American Parkinson Disease Association; Washington University Institute for Clinical and Translation Study; Jo Oertli Fund; Paula C. & Rodger Riney Parkinson Disease Fund; and Barnes-Jewish Hospital Foundation (Elliot Stein Family Fund and Parkinson Disease Research Fund).Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-1023.Corresponding Author: Joel S. Perlmutter, MD, Washington University School of Medicine, Campus Box 8111, 660 South Euclid Avenue, Saint Louis, MO 63110; e-mail, [email protected]wustl.edu.Current Author Addresses: Drs. Maiti and Perlmutter: Washington University School of Medicine, Campus Box 8111, 660 South Euclid Avenue, Saint Louis, MO 63110.This article was published at Annals.org on 31 March 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoIsradipine Versus Placebo in Early Parkinson Disease Metrics Cited byThe Role of Striatal Cav1.3 Calcium Channels in Therapeutics for Parkinson’s DiseaseParkinson's Disease: Risk Factor Modification and PreventionCalcium Channels and Selective Neuronal Vulnerability in Parkinson’s DiseaseNovel targeted therapies for Parkinson’s diseaseCalcium channels and iron metabolism: A redox catastrophe in Parkinson's disease and an innovative path to novel therapies?L-Type Calcium Channel Blockers: A Potential Novel Therapeutic Approach to Drug DependenceIsradipine plasma pharmacokinetics and exposure–response in early Parkinson’s diseaseSeeking a Magic Bullet–the search for new Parkinson’s disease therapeutic agents 5 May 2020Volume 172, Issue 9Page: 625-626KeywordsBrainCalcium channelsClinical trial reportingClinical trialsDisclosureDopaminergicsDrugsNeuronsParkinson diseaseStroke ePublished: 31 March 2020 Issue Published: 5 May 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. 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