Title: Quantitative Landscape Analysis of Disease-Modifying Parkinson’s Therapies in Preclinical Development
Authors: Jamir Pitton Rissardo, Ana Leticia Fornari Caprara
Conference: Planning for prevention of Parkinson's and related synucleinopathies: A trial design forum 2026, Phoenyx, AZ
Objective
To quantitatively describe therapeutic modalities, biological targets, and development stages within the preclinical Parkinson’s disease (PD) therapeutic pipeline using structured data mining of the Parkinson’s Hope List.
Background
Parkinson’s disease remains without an approved disease-modifying therapy despite increasing mechanistic understanding. The expanding number of investigational programs underscores the need for quantitative synthesis to identify dominant translational priorities and emerging therapeutic strategies.
Design/Methods
The November 2025 Parkinson’s Hope List was systematically reviewed. All research-stage entries were extracted and standardized. Programs were categorized by development stage, therapeutic modality, and mechanistic target using structured fields and keyword-based annotation of mechanism descriptions. Descriptive analyses were performed to quantify distributions and cross-relationships among categories.
Results
A total of 114 unique Parkinson’s disease research-stage therapeutic programs were identified, all designated as disease-modifying. Eighty programs (70.2%) were classified as preclinical, while thirty-four (29.8%) were in discovery. Therapeutic modalities were redominantly new chemical entities, accounting for 83 programs (72.8%). Additional modalities included 13 gene therapy programs (11.4%), 9 cell-based therapies (7.9%), 6 repurposed agents (5.3%), and 3 reformulated compounds (2.6%).Mechanistic analysis identified 13 programs targeting alpha-synuclein aggregation, propagation, or clearance, 10 targeting lysosomal or GBA-related pathways, 7 targeting inflammatory signaling including inflammasome or toll-like receptor pathways, 5 targeting LRRK2, 5 addressing mitochondrial dysfunction or mitophagy, 6 targeting microbiome-related mechanisms, and 7 employing immunotherapeutic strategies such as antibodies, vaccines, or immune cell modulation. Of the 13 gene therapy programs, 3 focused specifically on GBA-related approaches, while others targeted PARKIN, Klotho signaling, or RNA-based mechanisms.
Conclusions
This quantitative analysis demonstrates that the current Parkinson’s disease therapeutic pipeline is heavily weighted toward early-stage, disease-modifying strategies, with substantial convergence on proteostasis, lysosomal biology, immune signaling, mitochondrial integrity, and gut-brain axis mechanisms. The dominance of preclinical programs and small-molecule approaches highlights both the breadth of innovation and the substantial translational distance remaining before clinical validation.
Citation
Rissardo JP, Caprara ALF. Quantitative Landscape Analysis of Disease-Modifying Parkinson’s Therapies in Preclinical Development. J Parkinsons Dis 2026:14-15. doi: 10.1177/1877718X261441451.
Figure 1. Sankey diagram illustrating flow of PD programs from discovery/preclinical stages to therapeutic modalities and mechanistic targets.