New Challenges and Future Perspectives in Parkinson’s Disease and Motor Disorders

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neuromuscular and Movement Disorders".

Deadline for manuscript submissions: closed (8 October 2022) | Viewed by 7020

Special Issue Editor


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Interests: neurological disorders; stroke

Special Issue Information

Dear Colleagues,

“Parkinson’s disease (PD) is characterized by a range of motor and nonmotor symptoms. The classic motor features of PD, including akinesia, bradykinesia, resting tremor, and rigidity, are causally linked to the degeneration of midbrain dopaminergic neurons. In contrast, the pathophysiology of nonmotor symptoms, such as olfactory deficits, cognitive impairments, and neuropsychiatric symptoms, remains poorly understood.

The present Special Issue of Brain Sciences aims to collect international papers (research articles, narrative reviews, systematic reviews, meta-analyses, case studies) focused on the pathophysiology and treatment of motor  and nonmotor symptoms of PD.”

Dr. Hong-Yuan Chu
Guest Editor

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Published Papers (2 papers)

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Review

18 pages, 778 KiB  
Review
Recalibrating the Why and Whom of Animal Models in Parkinson Disease: A Clinician’s Perspective
by Andrea Sturchio, Emily M. Rocha, Marcelo A. Kauffman, Luca Marsili, Abhimanyu Mahajan, Ameya A. Saraf, Joaquin A. Vizcarra, Ziyuan Guo and Alberto J. Espay
Brain Sci. 2024, 14(2), 151; https://doi.org/10.3390/brainsci14020151 - 31 Jan 2024
Cited by 2 | Viewed by 1459
Abstract
Animal models have been used to gain pathophysiologic insights into Parkinson’s disease (PD) and aid in the translational efforts of interventions with therapeutic potential in human clinical trials. However, no disease-modifying therapy for PD has successfully emerged from model predictions. These translational disappointments [...] Read more.
Animal models have been used to gain pathophysiologic insights into Parkinson’s disease (PD) and aid in the translational efforts of interventions with therapeutic potential in human clinical trials. However, no disease-modifying therapy for PD has successfully emerged from model predictions. These translational disappointments warrant a reappraisal of the types of preclinical questions asked of animal models. Besides the limitations of experimental designs, the one-size convergence and oversimplification yielded by a model cannot recapitulate the molecular diversity within and between PD patients. Here, we compare the strengths and pitfalls of different models, review the discrepancies between animal and human data on similar pathologic and molecular mechanisms, assess the potential of organoids as novel modeling tools, and evaluate the types of questions for which models can guide and misguide. We propose that animal models may be of greatest utility in the evaluation of molecular mechanisms, neural pathways, drug toxicity, and safety but can be unreliable or misleading when used to generate pathophysiologic hypotheses or predict therapeutic efficacy for compounds with potential neuroprotective effects in humans. To enhance the translational disease-modification potential, the modeling must reflect the biology not of a diseased population but of subtypes of diseased humans to distinguish What data are relevant and to Whom. Full article
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11 pages, 1264 KiB  
Review
Pimavanserin and Parkinson’s Disease Psychosis: A Narrative Review
by Jamir Pitton Rissardo, Ícaro Durante, Idan Sharon and Ana Letícia Fornari Caprara
Brain Sci. 2022, 12(10), 1286; https://doi.org/10.3390/brainsci12101286 - 23 Sep 2022
Cited by 8 | Viewed by 5039
Abstract
Pimavanserin (PMV) is the first approved drug for treating hallucinations and delusions in Parkinson’s disease (PD) psychosis. Psychosis is one of the leading causes of nursing home placement in people with PD. Furthermore, hallucinations are a more frequent cause of institutionalization than motor [...] Read more.
Pimavanserin (PMV) is the first approved drug for treating hallucinations and delusions in Parkinson’s disease (PD) psychosis. Psychosis is one of the leading causes of nursing home placement in people with PD. Furthermore, hallucinations are a more frequent cause of institutionalization than motor disability or dementia related to PD. The management of PD psychosis involves antipsychotic medications. Most of the drugs in this class directly block dopamine D2 receptors, leading to significantly worsening motor symptoms in patients with PD. The most commonly used medications for managing PD psychosis are quetiapine, clozapine, and PMV. This literature review aims to study pimavanserin’s history, mechanism, clinical trials, and post-marketing experience. PMV is a potent 5-HT2A receptor antagonist/inverse agonist. Moreover, this drug can interact with 5-HT2C receptors. We calculated some physicochemical descriptors and pharmacokinetic properties of PMV. Eight clinical trials of PMV and PD psychosis are registered on ClinicalTrials.gov. Only four of them have complete results already published. Meta-analytic results showed that PMV efficacy is inferior to clozapine. However, PMV has a significantly lower number of side-effects for managing psychosis in PD. Medicare database assessment revealed 35% lower mortality with PMV compared to other atypical antipsychotics. Moreover, sensitive statistical analysis demonstrated that PMV is a protective factor for the risk of falls in individuals with PD. Full article
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