The PDR-001 trial is a first-in-human Phase 1 clinical study evaluating a novel gene therapy approach for Parkinson's disease that directly targets the pathological aggregation of alpha-synuclein. Unlike conventional symptomatic treatments, PDR-001 aims to modify the underlying disease process by delivering a peptide that promotes targeted degradation of alpha-synuclein aggregates in the brain.
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Overview
Mermaid diagram (expand to render)
The PDR-001 trial is a first-in-human Phase 1 clinical study evaluating a novel gene therapy approach for Parkinson's disease that directly targets the pathological aggregation of alpha-synuclein. Unlike conventional symptomatic treatments, PDR-001 aims to modify the underlying disease process by delivering a peptide that promotes targeted degradation of alpha-synuclein aggregates in the brain.
This trial represents a significant advancement in Parkinson's disease therapeutics, as it addresses the root cause of dopaminergic neuron death rather than merely managing symptoms["@tang2022"].
Trial Details
| Attribute | Value | |-----------|-------| | Phase | Phase 1 | | Status | Recruiting | | Sponsor | Ruijin Hospital (Shanghai, China) | | NCT Number | [NCT07157345](https://clinicaltrials.gov/study/NCT07157345) | | Intervention | PDR-001 (AAV9-packaged tat-βsyn-deg peptide) | | Delivery Method | Bilateral stereotactic injection into subthalamic nucleus (STN) | | Enrollment | 12 patients (estimated) | | Duration | 52 weeks | | Location | Ruijin Hospital, Shanghai, China | | Start Date | October 2025 (estimated) | | Completion Date | December 2029 (estimated) |
Mechanism of Action
The Challenge of Alpha-Synuclein Pathology
Parkinson's disease is characterized by the pathological aggregation of alpha-synuclein protein into Lewy bodies and Lewy neurites within dopaminergic neurons. This aggregation leads to:
Progressive loss of dopaminergic neurons in the substantia nigra
Disruption of neuronal function and synaptic transmission[@masliah2010]
Progressive motor and non-motor symptoms
PDR-001: Targeted Protein Degradation
PDR-001 (tat-βsyn-deg) is a three-segment peptide designed to selectively target alpha-synuclein for degradation:
Tat Transduction Domain: Enables cellular uptake and trafficking to the brain
Beta-synuclein Binding Domain: Specifically binds to alpha-synuclein
[ClinicalTrials.gov, PDR-001 Study (2025)](https://clinicaltrials.gov/study/NCT07157345)
[Tang et al., Alpha-synuclein aggregation and Parkinson's disease (2022)](https://doi.org/10.1186/s40478-022-01401-w)
[Masliah et al., Molecular mechanisms of synaptic dysfunction in Alzheimer's disease (2010)](https://doi.org/10.1016/j.febslet.2010.03.012)
Pathway Diagram
The following diagram shows the key molecular relationships involving PDR-001 Alpha-Synuclein Removal PD Trial discovered through SciDEX knowledge graph analysis: