Path: /clinical-trials/gra-myr-nd-nct07360977
Title: Myrosinase Bioactivated Glucoraphanin for Neurodegenerative Diseases (GRA-MYR-ND NCT07360977)
Tags: section:clinical-trials, kind:trial, disease:parkinsons, disease:multiple-sclerosis, intervention:glucoraphanin, intervention:sulforaphane, phase:phase-1-phase-2
| Field | Value |
|---|---|
| NCT Number | NCT07360977 |
| Official Title | A Composition Comprising Glucoraphanin, Myrosinase and a Buffered Solution for Use in the Treatment of Neurodegenerative Diseases |
| Acronym | GRA-MYR-ND |
| Phase | Phase 1/2 |
| Status | Recruiting |
| Study Type | Interventional |
| Allocation | Randomized |
| Intervention Model | Parallel |
| Enrollment | 300 participants (estimated) |
| Sponsor | IRCCS Centro Neurolesi Bonino Pulejo |
| Lead PI | Prof. Emanuela Mazzon |
| Start Date | January 2026 (estimated) |
| Estimated Completion | May 2026 |
| Location | Messina, Italy |
This is a randomized, parallel-group, open-label Phase 1/2 trial evaluating bioactivated glucoraphanin (GRA) — the sulforaphane precursor — in three patient cohorts:
| Arm | Type | Description |
|---|---|---|
| PD patients receiving standard therapy | Control | Parkinson's disease patients on standard therapy only |
| PD patients receiving bioactivated GRA | Experimental | 50 mg/day bioactivated GRA for 6 months |
| MS patients receiving standard therapy | Control | Multiple sclerosis patients on standard therapy only |
| MS patients receiving bioactivated GRA | Experimental | 50 mg/day bioactivated GRA for 6 months |
| Pediatric patients receiving standard therapy | Control | Standard therapy only |
| Pediatric patients receiving bioactivated GRA | Experimental | 10 mg/day bioactivated GRA for 6 months |
The therapeutic approach is based on the well-characterized Nrf2-activating properties of sulforaphane, the bioactive isothiocyanate derived from glucoraphanin hydrolysis by myrosinase:
Glucoraphanin + Myrosinase → Sulforaphane: The patented formulation ensures consistent conversion of the glucosinolate glucoraphanin to the active isothiocyanate sulforaphane through the inclusion of the plant enzyme myrosinase in a buffered solution[1].
Nrf2 Activation: Sulforaphane covalently modifies cysteine residues (Cys151, Cys273, Cys288) on Keap1, leading to release and nuclear translocation of Nrf2, which binds to Antioxidant Response Elements (ARE) to drive expression of over 250 cytoprotective genes[2].
Neuroprotective Effects: The trial is grounded in substantial preclinical evidence showing sulforaphane:
Multi-omic Biomarker Approach: The trial employs metabolomics and transcriptomics to characterize both the pharmacokinetics of glucoraphanin/sulforaphane and the downstream biological effects, which provides mechanistic validation of target engagement[4].
The key innovation in this trial is the use of bioactivated glucoraphanin — co-administered with myrosinase enzyme — rather than pre-formed sulforaphane:
Parkinson's Disease: PD is characterized by progressive loss of dopaminergic neurons in the substantia nigra, with oxidative stress, mitochondrial dysfunction, and neuroinflammation as key pathological drivers. Sulforaphane's multi-target neuroprotective profile addresses these mechanisms directly. The Nrf2 pathway is particularly relevant as it declines with aging — the primary risk factor for PD.
Multiple Sclerosis: MS involves demyelination and neurodegeneration in the central nervous system. Sulforaphane's effects on:
make it a compelling disease-modifying approach for MS.
Pediatric Neurodegenerative Conditions: The pediatric arm addresses rare neuromuscular and degenerative diseases where oxidative stress and neuroinflammation contribute to disease progression.
| Measure | Description | Timepoints |
|---|---|---|
| UPDRS Total Score | Unified Parkinson's Disease Rating Scale (0-260, higher = more disability) | Baseline, 6 months, 12 months |
| Hoehn and Yahr Scale | Disease progression staging (1-5) | Baseline, 6 months, 12 months |
| Non-Motor Symptoms Scale (NMSS) | 30 non-motor symptoms across 9 domains (0-360) | Baseline, 6 months, 12 months |
| PDQ-8 | Parkinson's Disease Quality of Life Questionnaire (0-100) | Baseline, 6 months, 12 months |
| PDSS-2 | Parkinson's Disease Sleep Scale (0-60) | Baseline, 6 months, 12 months |
| MoCA / MMSE | Cognitive assessment | Baseline, 6 months, 12 months |
| Hamilton Depression/Anxiety Scales | Mood assessment | Baseline, 6 months, 12 months |
| CGI-I / PGI-C | Global improvement scales | Baseline, 6 months, 12 months |
| Measure | Description | Timepoints |
|---|---|---|
| EDSS | Expanded Disability Status Scale (0-10) | Baseline, 6 months, 12 months |
| Brief Repeatable Battery (BRB) | Neuropsychological testing across 5 domains | Baseline, 6 months, 12 months |
| Normalized Brain Volume (NBV) | MRI-based brain atrophy measure | Baseline, 6 months, 12 months |
| Normalized Cortical Volume (NCV) | MRI-based cortical atrophy measure | Baseline, 6 months, 12 months |
| Whole-Brain Fractional Anisotropy (FA) | DTI measure of white matter integrity (0-1) | Baseline, 6 months, 12 months |
| Whole-Brain Mean Diffusivity (MD) | DTI measure of tissue destruction | Baseline, 6 months, 12 months |
| MoCA / MMSE | Cognitive assessment | Baseline, 6 months, 12 months |
| Measure | Description | Timepoints |
|---|---|---|
| Growth Parameters | Weight, height, BMI, Tanner staging | Baseline, 3, 6, 12 months |
| GMDS-3 | Griffiths Mental Development Scales | Baseline, 3, 6, 12 months |
| DOSS | Dysphagia Outcome and Severity Scale | Baseline, 3, 6, 12 months |
| EEG | Brain electrical activity analysis | Baseline, 3, 6, 12 months |
| High-Resolution Manometry | Esophageal motility assessment | Baseline, 3, 6, 12 months |
Inclusion:
Exclusion:
Inclusion:
Exclusion: Same as PD cohort
Inclusion:
Exclusion: Based on standard pediatric trial safety criteria
This trial builds directly on the substantial preclinical and clinical evidence for sulforaphane in neurodegeneration:
Mazzon E, et al. Myrosinase Bioactivated Glucoraphanin for the Treatment of Neurodegenerative Diseases (GRA-MYR-ND). ClinicalTrials.gov NCT07360977. 2025. ↩︎
Klomparens EA, Ding Y. The neuroprotective mechanisms and effects of sulforaphane. Brain Circulation. 2019. ↩︎
Schepici G, Bramanti P, Mazzon E. Efficacy of Sulforaphane in Neurodegenerative Diseases. Int J Mol Sci. 2020. ↩︎ ↩︎
Kamal RM, Abdull Razis AF, Mohd Sukri NS, et al. Beneficial Health Effects of Glucosinolates-Derived Isothiocyanates on Cardiovascular and Neurodegenerative Diseases. Molecules. 2022. ↩︎