Biomarkers for trials of neuroprotection in Parkinson's disease

Agarwal, Poojan; Stoessl, A. Jon

doi:10.1002/mds.25065

Cited by 22 publications

(14 citation statements)

References 162 publications

(307 reference statements)

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“…26 7 T MRI, novel MRI sequences that combine diffusion tensor imaging, T2*-weighted and whole-brain T1-weighted techniques, novel PET ligands, and transcranial ultrasound have all shown promise in identification of patients with PD, but imaging markers for PD are still at an early stage. 27 …”

Section: Difficulty Choosing the Most Effective Dosementioning

confidence: 97%

The ongoing pursuit of neuroprotective therapies in Parkinson disease

2014

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Many agents developed for neuroprotective treatment of Parkinson disease (PD) have shown great promise in the laboratory, but none have translated to positive results in patients with PD. Potential neuroprotective drugs, such as ubiquinone, creatine and PYM50028, have failed to show any clinical benefits in recent high-profile clinical trials. This 'failure to translate' is likely to be related primarily to our incomplete understanding of the pathogenic mechanisms underlying PD, and excessive reliance on data from toxin-based animal models to judge which agents should be selected for clinical trials. Restricted resources inevitably mean that difficult compromises must be made in terms of trial design, and reliable estimation of efficacy is further hampered by the absence of validated biomarkers of disease progression. Drug development in PD dementia has been mostly unsuccessful; however, emerging biochemical, genetic and pathological evidence suggests a link between tau and amyloid-β deposition and cognitive decline in PD, potentially opening up new possibilities for therapeutic intervention. This Review discusses the most important 'druggable' disease mechanisms in PD, as well as the most-promising drugs that are being evaluated for their potential efficiency in treatment of motor and cognitive impairments in PD.

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Section: Difficulty Choosing the Most Effective Dosementioning

confidence: 97%

The ongoing pursuit of neuroprotective therapies in Parkinson disease

2014

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“…Genomic and proteomic measurements are promising, but technically demanding. It is likely that in the near future a biomarker panel might be developed, possibly combing clinical batteries, imaging, and "omics"-based measures, as well as other disease-staterelated markers [77].…”

Section: Biomarkersmentioning

confidence: 99%

Pathogenesis-Targeted, Disease-Modifying Therapies in Parkinson Disease

2014

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Parkinson disease is an inexorably progressive neurodegenerative disorder. Multiple attempts have been made to establish therapies for Parkinson disease which provide neuroprotection or disease modification-two related, but not identical, concepts. However, to date, none of these attempts have succeeded. Many challenges exist in this field of research, including a complex multisystem disorder that includes dopaminergic and non-dopaminergic features; poorly understood and clearly multifaceted disease pathogenic mechanisms; a lack of reliable animal models; an absence of effective biomarkers of disease state, progression, and target engagement; and the confounding effects of potent symptomatic therapy. In this article, we will review previous, ongoing, and potential future trials designed to alter the progressive course of the disease from the perspective of the targeted underlying pathogenic mechanisms.

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“…131 Objective laboratory procedures would be highly desirable in PD diagnostics. Such new tools would be useful for cancer research and for studies into the basic mechanisms of mitophagy and mitochondrial bioenergetics.…”

Section: The Prediction Of Pdmentioning

confidence: 99%