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
Trial Overview
Mermaid diagram (expand to render)
| 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 |
Disease Targets
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Multiple Sclerosis](/diseases/multiple-sclerosis) - Relapsing-Remitting
- Pediatric Patients with Neuromuscular and Degenerative Diseases
Study Design
This is a randomized, parallel-group, open-label Phase 1/2 trial evaluating bioactivated glucoraphanin (GRA) — the sulforaphane precursor — in three patient cohorts:
Arms and Interventions
| 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 |
Mechanism of Action
The therapeutic approach is based on the well-characterized [Nrf2](/genes/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[@mazzon2024].
Nrf2 Activation: Sulforaphane covalently modifies cysteine residues (Cys151, Cys273, Cys288) on [Keap1](/proteins/keap1), leading to release and nuclear translocation of [Nrf2](/proteins/nrf2), which binds to Antioxidant Response Elements (ARE) to drive expression of over 250 cytoprotective genes[@klomparens2019].
Neuroprotective Effects: The trial is grounded in substantial preclinical evidence showing sulforaphane:
- Reduces oxidative stress in dopaminergic neurons
- Inhibits neuroinflammation through NF-κB suppression
- Enhances mitochondrial function
- Promotes clearance of protein aggregates (α-synuclein, amyloid-β)
- Improves cognitive function in neurodegenerative models[@schepici2020]
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[@kamal2022].Rationale
Why Glucoraphanin with Myrosinase?
The key innovation in this trial is the use of bioactivated glucoraphanin — co-administered with myrosinase enzyme — rather than pre-formed sulforaphane:
- Enhanced bioavailability: Myrosinase ensures conversion of glucoraphanin to sulforaphane in the GI tract, bypassing the variability of gut microbiome-dependent conversion
- Patent-protected: The formulation (EP2908850B1) is based on the combination of (Rs)-glucoraphanin with myrosinase in a buffered solution
- Differentiated from supplements: Standard glucoraphanin supplements lack consistent myrosinase activity, leading to unpredictable sulforaphane formation
Rationale for Each Indication
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:
- Oxidative stress reduction in oligodendrocytes
- Microglial activation suppression
- Myelin protection
- Nrf2-mediated anti-inflammatory effects
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.
Outcome Measures
Primary Outcomes
Parkinson's Disease Cohort
| 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 |
Multiple Sclerosis Cohort
| 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 |
Pediatric Cohort
| 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 |
Secondary Outcomes (All Cohorts)
- Metabolomics: LC-MS analysis of plasma and urine for glucoraphanin/sulforaphane pharmacokinetics, amino acid metabolites, SCFAs, MCFAs
- Transcriptomics: RNA-seq for differential gene expression analysis at baseline and 6 months
Eligibility Criteria
Parkinson's Disease Cohort
Inclusion:
- Age 45-75 years
- Clinical diagnosis of PD according to UK Brain Bank Criteria
- 3 months clinical stability before enrollment
- Anti-parkinsonian medication fixed for ≥3 months
Exclusion:
- Absolute contraindications to MRI
- Concomitant neurological disease or severe comorbidities (spinal injury, cancer, dementia, stroke, epilepsy, psychiatric disorders)
- MMSE score <24
- Participation in other clinical trials
- Pregnant/lactating
Multiple Sclerosis Cohort
Inclusion:
- Age ≥18 years
- Diagnosis of RR-MS according to McDonald criteria
- EDSS ≤5.5
- Stable disease for ≥30 days
- Stable disease-modifying therapy for ≥3 months
Exclusion: Same as PD cohort
Pediatric Cohort
Inclusion:
- Age 1-10 years
- Weight 5-30 kg
- Clinically stable condition
- Not enrolled in other clinical trials
Exclusion: Based on standard pediatric trial safety criteria
Collaborators and Funding
- Lead Institution: IRCCS Centro Neurolesi Bonino Pulejo (Messina, Italy)
- Collaborators:
- Fondazione Edmund Mach
- Vittore Buzzi Children's Hospital
- Azienda Sanitaria Provinciale Ragusa
- Funding: European Union - Next Generation EU - NRRP M6C2- Investment 2.1 (Grant: PNRR-POC-2022-12376049)
Connection to Existing Literature
This trial builds directly on the substantial preclinical and clinical evidence for sulforaphane in neurodegeneration:
- Preclinical evidence: Extensive animal model data showing neuroprotection in PD (MPTP, 6-OHDA models), MS (EAE model), and other neurodegenerative conditions[@schepici2020]
- Clinical translation: The formulation addresses the key limitation of prior sulforaphane trials — variability in bioactivation — by including exogenous myrosinase
- Multi-omic biomarkers: The inclusion of metabolomics and transcriptomics endpoints positions this trial to provide mechanistic validation of Nrf2 pathway activation in humans
Related Pages
- [Sulforaphane and Nrf2 Activation for Neuroprotection](/therapeutics/sulforaphane-nrf2-neuroprotection)
- [Nrf2 Signaling Pathway in Neurodegeneration](/mechanisms/nrf2-signaling-neurodegeneration)
- [NRF2-KEAP1 Oxidative Stress Response Pathway](/mechanisms/nrf2-keap1-pathway)
- [Parkinson's Disease Treatment Overview](/therapeutics/parkinsons-disease)
- [Multiple Sclerosis Mechanisms](/diseases/multiple-sclerosis)
References
[Mazzon E, et al. Myrosinase Bioactivated Glucoraphanin for the Treatment of Neurodegenerative Diseases (GRA-MYR-ND). ClinicalTrials.gov NCT07360977 (2025)](https://clinicaltrials.gov/study/NCT07360977)
[Klomparens EA, Ding Y. The neuroprotective mechanisms and effects of sulforaphane. Brain Circ. 2019 Apr-Jun;5(2):74-83](https://pubmed.ncbi.nlm.nih.gov/33007212/)
[Schepici G, Bramanti P, Mazzon E. Efficacy of Sulforaphane in Neurodegenerative Diseases. Int J Mol Sci. 2020 Nov 16;21(22):8637](https://pubmed.ncbi.nlm.nih.gov/33207780/)
[Kamal RM, Abdull Razis AF, Mohd Sukri NS, et al. Beneficial Health Effects of Glucosinolates-Derived Isothiocyanates on Cardiovascular and Neurodegenerative Diseases. Molecules. 2022 Jan 19;27(3):624](https://pubmed.ncbi.nlm.nih.gov/35163897/)
[Deuschl G, et al. The burden of neurological diseases in Europe: an analysis for the Global Burden of Disease Study 2017. Lancet Public Health. 2020 Oct;5(10):e551-e567](https://pubmed.ncbi.nlm.nih.gov/31334360/)
[Yadav SK, Soin D, Ito K, Dhib-Jalbut S. Insight into the mechanism of action of dimethyl fumarate in multiple sclerosis. J Mol Med (Berl). 2019 Apr;97(4):463-472](https://pubmed.ncbi.nlm.nih.gov/30820593/)