Introduction: To date, no drug has demonstrated clinically indisputable neuroprotective efficacy in Parkinson's disease (PD). We also have no effective symptomatic treatment for disabling symptoms such as balance problems, and dementia, and we need to improve the efficacy and safety profile of drugs currently used in the management of motor complications.
Areas Covered: We examine the agents which appear to have most therapeutic promise based on concepts, feasibility in a reasonable time frame, and available clinical data and place an emphasis on disease-modifying treatments. PUBMED and Clinicaltrials.gov databases were searched for Phase I and II randomized trials for symptomatic or disease-modifying treatments considering only studies that began since 2010 or that were completed after 2015, up to 30 April 2020.
Expert Opinion: Encouraging progress has been made in our understanding of molecular pathways. We find passive immunization approaches against α-synuclein, LRRK2 kinase inhibitors, and treatment that can increase GCase activity, which have shown some efficacy on both GBA-mutated and non-mutated PD patients. The recognition of non-dopaminergic impairment and the prominent role of non-motor symptoms have prompted the development of trials on compounds that could tackle different neurotransmitter systems. Future approaches will encompass more personalized medicine strategies based on molecular signatures and non-motor phenotypes.
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http://dx.doi.org/10.1080/13543784.2020.1814252 | DOI Listing |
Dokl Biol Sci
January 2025
Research Center of Neurology, Moscow, Russia.
Characteristic patterns of UV-induced skin autofluorescence were determined for patients with Parkinson's disease (PD) and associated with dysmetabolic alterations, such as nonenzymatic protein glycation, an increase in extracellular matrix stiffness, impaired metabolism of tissue fluorophores, mitochondrial dysfunction, and accumulation of aberrant proteins. Key differences in skin autofluorescence spectra were for the first time observed in PD, making it possible to discriminate between PD patients and healthy persons or individuals without signs of chronic neurodegeneration. Namely, skin fluorescence related to the reflected signal upon excitation with UV light at 375 nm was lower in PD patients.
View Article and Find Full Text PDFNeurosurg Rev
January 2025
Department of Neurosurgery, Hospital Universitario Fundación Jiménez Díaz, Av. De los Reyes Católicos, 2, Madrid, 28040, Spain.
Matched-controlled long-term disease evaluation and neuropsychological outcomes derived from deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson´s disease (PD) are lacking, with inconsistent results regarding the cognitive impact of this procedure. Here we study the long-term effects associated to DBS comparing outcomes with a matched control group. A prospective observational study of 40 patients with PD with bilateral STN-DBS, with a mean follow-up of 9 (6-12) years was conducted.
View Article and Find Full Text PDFCell Biol Toxicol
January 2025
Department of Environmental Medicine, School of Medicine, Chongqing University, Chongqing, China.
Manganese (Mn) is a neurotoxin that has been etiologically linked to the development of neurodegenerative diseases in the case of overexposure. It is widely accepted that overexposure to Mn leads to manganism, which has clinical symptoms similar to Parkinson's disease (PD), and is referred to as parkinsonism. Astrocytes have been reported to scavenge and degrade extracellular α-synuclein (α-Syn) in the brain.
View Article and Find Full Text PDFJ Neural Transm (Vienna)
January 2025
Department of Neurology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
Parkinson's disease (PD) is a chronic neurodegenerative disease of the elderly. Patients suffer from progressive motor and non-motor symptoms. Further, PD patients often present geriatric features like multimorbidity and polypharmacotherapy.
View Article and Find Full Text PDFMov Disord Clin Pract
January 2025
Sorbonne Université, Institut du Cerveau-Paris Brain Institute-ICM, Hôpital de la Salpêtrière, INSERM, CNRS, Paris, France.
Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and nonmotor symptoms, with a significant genetic component. Early-onset Parkinson's disease (EOPD), manifesting before age 45, is often linked to mutations in genes such as PARK2, PINK1, and PARK7, the latter coding for the protein DJ-1.
Objective: We present the first reported cases of EOPD carrying a previously undescribed homozygous PARK7 mutation, p.
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