@article{5c5f3c75b8ab43e7bfd868348c0ad43f,
title = "Calcium, mitochondrial dysfunction and slowing the progression of Parkinson's disease",
abstract = "Parkinson's disease is characterized by progressively distributed Lewy pathology and neurodegeneration. The motor symptoms of clinical Parkinson's disease (cPD) are unequivocally linked to the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Several features of these neurons appear to make them selectively vulnerable to factors thought to cause cPD, like aging, genetic mutations and environmental toxins. Among these features, Ca2 + entry through Cav1 channels is particularly amenable to pharmacotherapy in early stage cPD patients. This review outlines the linkage between these channels, mitochondrial oxidant stress and cPD pathogenesis. It also summarizes considerations that went into the design and execution of the ongoing Phase 3 clinical trial with an inhibitor of these channels – isradipine.",
keywords = "Calcium, Clinical trial, Dihydropyridine, Dopaminergic neurons, Parkinson's disease, Patch clamp, Physiology",
author = "Surmeier, {D. James} and Halliday, {Glenda M.} and Tanya Simuni",
note = "Funding Information: This work was supported by NIH grant NS047085 and grants from the JPB Foundation and IDP Foundation to DJS. The STEADY-PD III is supported by NIH grant U01NS080818 and biomarker substudy by the MJFF. GMH is a National Health and Medical Research Council of Australia Senior Principal Research Fellow (grant #1079679). Funding Information: Dr. Surmeier serves on scientific advisory boards of Pfizer and Adamas Pharmaceuticals. He serves as a consultant for Lundbeck Neuroscience. Dr. Surmeier receives research funding from NIH, MJFF, the JPB Foundation, CHDI, IDP Foundation and Adamas Pharmaceuticals. Funding Information: Dr. Surmeier serves on scientific advisory boards of Pfizer and Adamas Pharmaceuticals. He serves as a consultant for Lundbeck Neuroscience. Dr. Surmeier receives research funding from NIH , MJFF , the JPB Foundation , CHDI , IDP Foundation and Adamas Pharmaceuticals . Funding Information: Dr. Halliday serves on the scientific advisory board of DANDRITE; has been a consultant for the NHMRC, GSK and Lundbeck Neuroscience; received conference travel funds from AAIC, Int Soc Neurochemistry, Int DLB Conference, AAN, Int MSA Conference, NHMRC National Institute for Dementia Research, 2nd Chinese Brain Banking Meeting, Japanese Neuroscience Soc; receives royalties from Academic Press, Elsevier & Oxford University Press; receives research grant funding from NHMRC ( 1008307 , 1037746 & 1079679 ), Michael J. Fox Foundation , Shake-it-up Australia , Parkinson's NSW , and the Universities of Sydney & NSW (infrastructure & equipment). Funding Information: As a first step toward a disease modification trial, the safety of isradipine was tested in Phase Ib and Phase II studies in early stage cPD patients. These studies found that isradipine had acceptable safety and tolerability at doses of 10 mg/day or less ( Parkinson Study Group, 2013; Simuni et al., 2010 ). The combination of the preclinical rationale, epidemiological data linking DHPs to reduced risk of cPD and the Phase Ib/II safety data motivated NIH to mount a 5 year, Phase III, disease modification clinical trial of isradipine in early stage cPD (STEADY-PD III, clintrials.gov NCT02168842 ). The study is being conducted at 57 Parkinson Study Group (PSG) sites in North America and is funded by the National Institute of Neurological Disorders and Stroke (NINDS) and the Michael J. Fox Foundation. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = dec,
doi = "10.1016/j.expneurol.2017.08.001",
language = "English (US)",
volume = "298",
pages = "202--209",
journal = "Neurodegeneration",
issn = "0014-4886",
publisher = "Academic Press Inc.",
}