Myrosinase Bioactivated Glucoraphanin for Neurodegenerative Diseases (GRA-MYR-N…

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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Disease Targets

• Parkinson’s Disease

• 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

Mechanism of Action

The therapeutic approach is based on the well-characterized Nrf2-activating properties of sulforaphane, the bioactive isothiocyanate derived from glucoraphanin hydrolysis by myrosinase:

1. 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^{1Myrosinase Bioactivated Glucoraphanin for the Treatment of Neurodegenerative Diseases (GRA-MYR-ND)2025 · ClinicalTrials.gov NCT07360977Open reference}.

2. 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^{2The neuroprotective mechanisms and effects of sulforaphane2019 · Brain Circulation · PMID 33007212Open reference}.

3. 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^{3Efficacy of Sulforaphane in Neurodegenerative Diseases2020 · Int J Mol Sci · PMID 33207780Open reference}

4. 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^{4Beneficial Health Effects of Glucosinolates-Derived Isothiocyanates on Cardiovascular and Neurodegenerative Diseases2022 · Molecules · PMID 35163897Open reference}.

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

Multiple Sclerosis Cohort

Pediatric Cohort

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^{3Efficacy of Sulforaphane in Neurodegenerative Diseases2020 · Int J Mol Sci · PMID 33207780Open reference}

• 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

• Nrf2 Signaling Pathway in Neurodegeneration

• NRF2-KEAP1 Oxidative Stress Response Pathway

• Parkinson’s Disease Treatment Overview

• Multiple Sclerosis Mechanisms