Journal of movement disordersFeb 6, 2025

Using Existing Drugs to Find Treatments That Slow Parkinson's Disease Progression

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jan 20, 2026

Abstract

No disease-modifying therapies have been identified to slow or arrest neurodegeneration in Parkinson's disease (PD).

Parkinson's disease is marked by the loss of dopaminergic and nondopaminergic neurons and the presence of Lewy bodies composed of aggregated α-synuclein.
Challenges in developing effective therapies include disease heterogeneity and the lack of reliable biomarkers.
Existing drugs are being repurposed to create new therapeutic applications, which may reduce development time and risk.
Potential candidates for repurposing include glucagon-like peptide-1 receptor agonists, statins, and iron-chelating agents.
While early studies show promise, many phase III trials have produced unfavorable results, indicating the complexity of PD's underlying mechanisms.

Simplified

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder and is characterized by progressive dopaminergic and nondopaminergic neuronal loss and the presence of Lewy bodies, which are primarily composed of aggregated α-synuclein. Despite advancements in symptomatic therapies, such as dopamine replacement and deep brain stimulation, no disease-modifying therapies (DMTs) have been identified to slow or arrest neurodegeneration in patients with PD. Challenges in DMT development include disease heterogeneity, the absence of reliable biomarkers, and the multifaceted pathophysiology of PD, encompassing neuroinflammation, mitochondrial dysfunction, lysosomal impairment, and oxidative stress. and repurposing strategies using existing drugs for new therapeutic applications offer promising approaches to accelerate the development of DMTs for PD. These strategies minimize time, cost, and risk by using compounds with established safety profiles. Prominent candidates include glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, ambroxol, calcium channel blockers, statins, iron-chelating agents, c-Abl inhibitors, and memantine. Although preclinical and early clinical studies have demonstrated encouraging results, numerous phase III trials have yielded unfavorable outcomes, elucidating the complexity of PD pathophysiology and the need for innovative trial designs. This review evaluates the potential of prioritized repurposed drugs for PD, focusing on their mechanisms, preclinical evidence, and clinical trial outcomes, and highlights the ongoing challenges and opportunities in this field.

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Competing interests

Conflicts of Interest . The authors have no financial conflicts of interest.

PubMed

Using Existing Drugs to Find Treatments That Slow Parkinson's Disease Progression

Abstract

Full Text

Funding

Competing interests

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