Myrosinase Bioactivated Glucoraphanin for Neurodegenerative Diseases (GRA-MYR-ND NCT07360977)

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Myrosinase Bioactivated Glucoraphanin for Neurodegenerative Diseases (GRA-MYR-ND NCT07360977)

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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

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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

[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/)

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📊 Evidence Profile Foundational

Evidence Balance

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Certainty

60%

Debates

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Incoming

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Outgoing

12

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📗 Cite This Artifact

Myrosinase Bioactivated Glucoraphanin for Neurodegenerative Diseases (GRA-MYR-ND NCT07360977)

Trial Overview

Trial Overview

Disease Targets

Study Design

Arms and Interventions

Mechanism of Action

Rationale

Why Glucoraphanin with Myrosinase?

Rationale for Each Indication

Outcome Measures

Primary Outcomes

Parkinson's Disease Cohort

Multiple Sclerosis Cohort

Pediatric Cohort

Secondary Outcomes (All Cohorts)

Eligibility Criteria

Parkinson's Disease Cohort

Multiple Sclerosis Cohort

Pediatric Cohort

Collaborators and Funding

Connection to Existing Literature

References

💬 Discussion

📗 Cite This Artifact

Myrosinase Bioactivated Glucoraphanin for Neurodegenerative Diseases (GRA-MYR-ND NCT07360977)

Trial Overview

Trial Overview

Disease Targets

Study Design

Arms and Interventions

Mechanism of Action

Rationale

Why Glucoraphanin with Myrosinase?

Rationale for Each Indication

Outcome Measures

Primary Outcomes

Parkinson's Disease Cohort

Multiple Sclerosis Cohort

Pediatric Cohort

Secondary Outcomes (All Cohorts)

Eligibility Criteria

Parkinson's Disease Cohort

Multiple Sclerosis Cohort

Pediatric Cohort

Collaborators and Funding

Connection to Existing Literature

Related Pages

References

💬 Discussion