A Review of the Recent Advances in the Pharmacological Management of Parkinson’s Disease

TL;DR

This review discusses current and emerging drug treatments for Parkinson's disease, emphasizing the need for better long-term solutions.

Contribution

The paper provides a comprehensive overview of recent pharmacological advances and highlights the need for innovative strategies in PD treatment.

Findings

Levodopa remains the gold standard for motor symptom management in PD.

Current therapies face diminishing long-term efficacy and severe adverse effects.

Emerging treatments include neuroprotective strategies like gene therapy and alpha-synuclein-targeting immunotherapy.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, leading to motor and nonmotor symptoms. The pathophysiology of PD involves a complex interplay of genetic, environmental, and biochemical factors, including the accumulation of alpha-synuclein protein aggregates, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Current pharmacological treatments primarily focus on alleviating symptoms, with levodopa (LD) being the gold standard for motor symptom management. Additionally, DOPA decarboxylase (DDC) enzyme inhibitors, dopamine agonists (DA), monoamine oxidase B (MAO-B) inhibitors, catechol-O-methyl transferase (COMT) inhibitors, and centrally acting anticholinergics are employed to modulate dopaminergic/cholinergic signaling and improve quality of life. Despite these advances, the long-term efficacy of existing therapies diminishes over time and presents with severe adverse effects, necessitating the exploration of novel therapeutic approaches. Future drug treatments should aim to address disease progression through neuroprotective strategies, such as gene therapy, immunotherapy targeting alpha-synuclein, and neurorestorative approaches that promote neurogenesis and synaptic plasticity. There are some limitations to consider with these novel therapies, such as current preclinical or early clinical phases with small sample sizes and follow-up trials. This narrative review aims to provide insight into the existing and emerging pharmacological treatment options for the management of PD, while highlighting the need for innovative strategies to improve outcomes for individuals living with PD, comparing the benefits versus risks.

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