Planning for Prevention of Parkinson Disease

Crotty, Grace F.; Keavney, Jessi L.; Alcalay, Roy N.; Marek, Kenneth; Marshall, Gad A.; Rosas, H. Diana; Schwarzschild, Michael A.

doi:10.1212/wnl.0000000000200789

Cited by 14 publications

(12 citation statements)

References 55 publications

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“…Multiple key design elements of a PD prevention trial are just now beginning to come into focus, as reflected in the first convening of an international conference on planning for such trials this year. 18 Nevertheless, early pharmacologic candidates may now be reasonably proposed for testing based on the above principles. Not only do they offer realistic prospects for slowing the pathophysiology of PD before diagnosis but proceeding with their testing may also be of great value in establishing proof-of-concept and a methodological foundation for future prevention trials.…”

Section: Prototypic Drug Candidates For Early Pd Prevention Trialsmentioning

confidence: 99%

What to Test in Parkinson Disease Prevention Trials?

Crotty

Schwarzschild

2022

Neurology

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Despite the sound epidemiologic and basic science rationales underpinning numerous “disease modification” trials in manifest Parkinson disease (PD), none has convincingly demonstrated that a treatment slows progression. Rapidly expanding knowledge of the genetic determinants and prodromal features of PD now allows realistic planning of prevention trials with initiation of putatively neuroprotective therapies earlier in the disease. In this article, we outline the principles of drug selection for PD prevention trials, focused on proof-of-concept opportunities that will help establish a methodological foundation for this fledgling field. We describe prototypical, relatively low-risk drug candidates for such trials (e.g., albuterol, ambroxol, caffeine, ibuprofen), tailored to specific at-risk populations ranging from pathogenic LRRK2 or GBA gene variant carriers to those defined by prodromal PD and α-synucleinopathy. Finally, we review gene-targeted approaches currently in development targeting clinically manifest PD for their potential in future prevention trials.

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Section: Prototypic Drug Candidates For Early Pd Prevention Trialsmentioning

confidence: 99%

What to Test in Parkinson Disease Prevention Trials?

Crotty

Schwarzschild

2022

Neurology

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“…Although tremendous progress has been made in the development of treatments for PD, such as pharmacological dopamine substitution (L-DOPA treatment) and deep brain stimulation, none of these treatments is curative. Considering the limited effectiveness of current available treatments, identification of modifiable lifestyle factors for PD prevention is imperative [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Physical activity and sleep pattern in relation to incident Parkinson’s disease: a cohort study

Chen,

Sun,

et al. 2024

Int J Behav Nutr Phys Act

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Background How physical activity (PA) and different sleep traits and overall sleep pattern interact in the development of Parkinson’s disease (PD) remain unknown. Objective To prospectively investigate the joint associations of PA and sleep pattern with risk of PD. Methods Included were 339,666 PD-free participants from the UK Biobank. Baseline PA levels were grouped into low (< 600 MET-mins/week), medium (600 to < 3000 MET-mins/week) and high (≥ 3000 MET-mins/week) according to the instructions of the UK Biobank. Healthy sleep traits (chronotype, sleep duration, insomnia, snoring, and daytime sleepiness) were scored from 0 to 5 and were categorized into “ideal sleep pattern” (≥ 3 sleep scores) and “poor sleep pattern” (0–2 sleep scores). Hazard ratios (HRs) and 95% confidence intervals (CIs) of PD were estimated by Cox proportional hazards models. Results During a median of 11.8 years of follow-up, 1,966 PD events were identified. The PD risk was lower in participants with high PA (HR = 0.73; 95% CI: 0.64, 0.84), compared to those with low PA; and participants with ideal sleep pattern also had a lower risk of PD (HR = 0.78; 95% CI: 0.69, 0.87), compared to those with poor sleep pattern. When jointly investigating the combined effect, participants with both high PA and ideal sleep pattern had the lowest risk of incident PD (HR = 0.55; 95% CI: 0.44, 0.69), compared to those with low PA and poor sleep pattern; notably, participants with high PA but poor sleep pattern also gained benefit on PD risk reduction (HR = 0.74; 95% CI: 0.55, 0.99). Conclusions Both high PA and ideal sleep pattern were independently associated with lower risk of developing PD, and those with both high PA level and ideal sleep pattern had the lowest risk. Our results suggest that improving PA levels and sleep quality may be promising intervention targets for the prevention of PD.

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“…Parkinson's disease (PD) is a dreadful and escalating brain illness that affects 1%–3% of people above 55 years of age. Interestingly, over the past couple of decades, a range of advancements have recognized certain populations at a higher chance of developing PD (Crotty et al, 2022; de Lau & Breteler, 2006). The motor symptoms of the disorder such as; tremors, instability, and muscle rigidity, arise due to the dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc) (Goyal et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic implications of crocin in Parkinson's disease: A review of preclinical research

et al. 2023

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Parkinson's disease is among the most common forms of neurodegenerative illness, with present treatment being primarily symptomatic and frequently coming with substantial adverse effects. Neuronal degeneration may arise due to a variety of pathological events, like inflammatory responses, neurotransmitter dysregulation, oxidative damage, mitochondrial malfunction, apoptosis, and genetic factors. The health issue and financial burden brought on by Parkinson's disease can worsen as the population ages. In the search for new and secure therapeutic agents for Parkinson's disease, several natural compounds have been shown to exert considerable neuroprotective benefits. Crocin, a naturally occurring carotenoid molecule, was found to have neuroprotective potential in the therapy of this disorder. Taking into account, the outcomes of various studies and the restorative actions of crocin, the present study emphasized the protective ability of crocin in this disease. Given the strong evidence supporting the neuroprotective ability of crocin, it is inferred that crocin inhibits inflammatory, apoptotic, and antioxidant processes through multiple mechanisms. Therefore, this compound is considered a safe and effective therapeutic choice for neurodegenerative illnesses like Parkinson's disease. However, more research on its efficacy as a treatment of Parkinson's disease is needed, specifically examining its mechanisms and the results obtained in clinical trials.

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Planning for Prevention of Parkinson Disease

Cited by 14 publications

References 55 publications

What to Test in Parkinson Disease Prevention Trials?

What to Test in Parkinson Disease Prevention Trials?

Physical activity and sleep pattern in relation to incident Parkinson’s disease: a cohort study

Therapeutic implications of crocin in Parkinson's disease: A review of preclinical research

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