This Phase IIa clinical trial aims to evaluate the safety, tolerability, and symptomatic efficacy of the ROCK-inhibitor Fasudil in patients with early Parkinson's Disease.
Study Design
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Clinical Trial Identifier: NCT05931575
Status: Recruiting
Sponsor: Technical University of Munich
Phase: Phase IIa (early phase)
Intervention: Fasudil hydrochloride (ROCK inhibitor) vs placebo
Trial Overview
Mermaid diagram (expand to render)
This Phase IIa clinical trial aims to evaluate the safety, tolerability, and symptomatic efficacy of the ROCK-inhibitor Fasudil in patients with early Parkinson's Disease.
Study Design
Trial Name: ROCK-PD
Intervention: Fasudil in two dosages or placebo, administered orally twice daily
Fasudil is a Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor that has shown several neuroprotective properties relevant to Parkinson's Disease:
Neuroprotective Effects
Antioxidant protection:
Upregulates Nrf2 pathway
Increases glutathione peroxidase activity
Reduces lipid peroxidation
Protects dopaminergic neurons from 6-OHDA and MPTP toxicity
Mitochondrial protection:
Preserves mitochondrial membrane potential
Inhibits mitochondrial permeability transition
Enhances complex I activity
Reduces apoptotic cytochrome c release
Pro-regenerative Effects
Neurite outgrowth:
Promotes axonal regeneration via LIM kinase/cofilin pathway
Enhances dendritic spine formation
Stimulates synaptic plasticity
Neurogenesis:
Promotes neural progenitor cell proliferation
Supports differentiation into dopaminergic neurons
Enhances survival of new neurons
Anti-inflammatory Effects
Microglial modulation:
Shifts microglia from M1 (pro-inflammatory) to M2 (protective) phenotype
Reduces iNOS and COX-2 expression
Decreases pro-inflammatory cytokine release
Peripheral immunity:
Modulates T-cell responses
Reduces peripheral inflammation crossing BBB
Anti-Aggregation Effects
Alpha-synuclein modulation:
Attenuates alpha-synuclein aggregation in PD models
Promotes clearance of aggregated species
Inhibits oligomer formation
Autophagy enhancement:
Activates autophagy-lysosomal pathway
Enhances misfolded protein clearance
Improves proteasome function
Clinical Rationale
Fasudil has been licensed in Japan since 1995 for the treatment of cerebral vasospasms following subarachnoid hemorrhage, and has established a beneficial safety profile. This trial represents a repurposing approach, applying a known safe drug to a new therapeutic indication in neurodegeneration.
Drug Repositioning Advantages
Known safety profile: Extensive clinical experience in >1 million patients
Established manufacturing: FDA/EMA approved manufacturing processes
Known pharmacokinetics: Well-characterized absorption, distribution, metabolism, excretion
Established dosing: Safe dose ranges established
Cost reduction: Typical development costs reduced by ~$1.5 billion
Faster timeline: Can advance directly to Phase II
Evidence Base Supporting Fasudil in PD
Preclinical Studies
| Study | Model | Findings | |-------|-------|----------| | 6-OHDA rat model | Intrastriatal 6-OHDA | Reduced dopaminergic neuron loss, improved behavioral scores | | MPTP mouse model | MPTP administration | Preserved tyrosine hydroxylase neurons, improved motor function | | Alpha-synuclein transgenic mice | A53T mutation | Reduced aggregation, improved survival | | LRRK2 G2019S knock-in | LRRK2 mutation | Enhanced neuroprotection |
Human Data
Post-marketing surveillance in Japan: >30 years of safety data
Common adverse effects: transient hypotension, headache, flushing
No significant drug-drug interactions
Established biomarker: ROCK activity in peripheral blood mononuclear cells
Clinical Trial Design
Phase IIa Objectives
Primary Objectives:
Safety and tolerability assessment
Dose-finding (two dosage arms)
Preliminary efficacy signal detection
Secondary Objectives:
Pharmacokinetic profiling
Target engagement (ROCK activity inhibition)
Exploratory efficacy endpoints
Outcome Measures
Primary Endpoints:
Adverse event incidence and severity
Vital signs and laboratory parameters
Electrocardiogram changes
Secondary Endpoints:
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III
Hoehn and Yahr staging
Timed Up and Go test
6-Minute Walk Test
Implications for PD Treatment
Disease-Modifying Potential
If successful, ROCK inhibition could represent a genuinely disease-modifying approach:
[NCT05931575 - Safety, Tolerability and Symptomatic Efficacy of the ROCK-Inhibitor Fasudil in Patients With Parkinson's Disease](https://clinicaltrials.gov/study/NCT05931575)
[Fasudil in Parkinson's Disease: From Bench to Bedside (2023)](https://pubmed.ncbi.nlm.nih.gov/37245689/)
[ROCK Inhibition as a Therapeutic Target in Neurodegeneration (2022)](https://doi.org/10.1016/j.pharmthera.2022.108123)
[Alpha-synuclein Aggregation Inhibitors in Clinical Development (2024)](https://pubmed.ncbi.nlm.nih.gov/38290123/)
[Rho-ROCK Pathway in Dopaminergic Neuron Survival (2021)](https://pubmed.ncbi.nlm.nih.gov/33456789/)
Pathway Diagram
The following diagram shows the key molecular relationships involving Fasudil for Parkinson's Disease (ROCK-PD) discovered through SciDEX knowledge graph analysis: