Myrosinase Bioactivated Glucoraphanin for Neurodegenerative Diseases (NCT07360977)

Myrosinase Bioactivated Glucoraphanin for Neurodegenerative Diseases

Clinical Trial Identifier: [NCT07360977](https://clinicaltrials.gov/study/NCT07360977)

Trial Overview

| Field | Value |
|-------|-------|
| NCT Number | NCT07360977 |
| Phase | Phase 1/2 |
| Status | Recruiting |
| Sponsor | IRCCS Centro Neurolesi Bonino Pulejo |
| Condition | Neurodegenerative Disease |
| Intervention | Myrosinase Bioactivated Glucoraphanin |
| Participants | TBD |

Study Description

Myrosinase Bioactivated Glucoraphanin for Neurodegenerative Diseases

Clinical Trial Identifier: [NCT07360977](https://clinicaltrials.gov/study/NCT07360977)

Trial Overview

| Field | Value |
|-------|-------|
| NCT Number | NCT07360977 |
| Phase | Phase 1/2 |
| Status | Recruiting |
| Sponsor | IRCCS Centro Neurolesi Bonino Pulejo |
| Condition | Neurodegenerative Disease |
| Intervention | Myrosinase Bioactivated Glucoraphanin |
| Participants | TBD |

Study Description

This clinical trial investigates the neuroprotective potential of myrosinase bioactivated glucoraphanin, a compound derived from cruciferous vegetables that is converted to sulforaphane through enzymatic activation. The trial evaluates whether this glucosinolate-derived approach can provide therapeutic benefits in neurodegenerative diseases.

Mechanism of Action

Glucosinolate Pathway

Glucoraphanin (also known as sulforaphane glucosinolate) is a naturally occurring compound in cruciferous vegetables such as broccoli, cauliflower, and Brussels sprouts. When incubated with myrosinase—an enzyme also present in these vegetables—the glucoraphanin is converted to bioactive sulforaphane (SFN).

The conversion process:

• Glucoraphanin + Myrosinase → Sulforaphane (isothiocyanate)
• This activation step is crucial for biological activity

Neuroprotective Mechanisms

Nrf2 Activation:
Sulforaphane is one of the most potent known activators of the Nrf2 (Nuclear factor erythroid 2–related factor 2) transcription factor pathway. Nrf2 regulates the expression of antioxidant and cytoprotective genes, including:

• Heme oxygenase-1 (HO-1)
• NAD(P)H quinone dehydrogenase 1 (NQO1)
• Glutamate-cysteine ligase (GCL)
• Thioredoxin reductase (TrxR)

• Anti-inflammatory: Suppresses NF-κB signaling and reduces pro-inflammatory cytokines
• Mitochondrial protection: Enhances mitochondrial function and biogenesis
• Protein homeostasis: Activates autophagy and proteasome pathways
• Anti-apoptotic: Modulates Bcl-2 family proteins and caspase inhibition

Scientific Rationale

Oxidative Stress in Neurodegeneration

[Neurodegenerative diseases](/diseases/neurodegeneration) including [Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's disease](/diseases/parkinsons-disease), and [ALS](/diseases/amyotrophic-lateral-sclerosis) share a common feature: progressive accumulation of oxidative damage. The brain's high metabolic rate, lipid content, and limited antioxidant capacity make it particularly vulnerable to reactive oxygen species (ROS)[@zhao2021].

Key observations:

• Elevated markers of oxidative stress in post-mortem brain tissue
• Reduced antioxidant enzyme activity in affected regions
• Genetic variants in antioxidant genes associated with disease risk

Nrf2 as Therapeutic Target

The Nrf2 pathway represents a master regulator of cellular defense:

• Under basal conditions: Nrf2 is bound by Keap1 and targeted for degradation
• Upon oxidative stress: Nrf2 translocates to the nucleus and activates antioxidant response element (ARE) genes
• Therapeutic activation: Pharmacological Nrf2 activators can induce protective gene expression

• Covalently modifies Keap1, releasing Nrf2
• Has been used safely in humans for decades as a dietary supplement
• Crosses the blood-brain barrier
• Demonstrated neuroprotective effects in multiple preclinical models

Preclinical Evidence

Alzheimer's Disease Models

In APP/PS1 transgenic mice:

• Reduced Aβ plaque burden with sulforaphane treatment
• Improved cognitive performance in Morris water maze
• Decreased markers of oxidative stress (8-OHdG, 4-HNE)
• Enhanced autophagy markers

Parkinson's Disease Models

In MPTP and 6-OHDA models:

• Protected dopaminergic neurons from toxicity
• Reduced behavioral deficits
• Decreased α-synuclein aggregation
• Improved mitochondrial function

ALS Models

In SOD1 transgenic mice:

• Delayed disease onset
• Extended survival
• Reduced motor neuron degeneration
• Decreased oxidative stress markers

Clinical Development

Previous Human Studies

Sulforaphane has been evaluated in several clinical settings:

• Cancer prevention: Well-tolerated at doses up to 100 μmol
• Asthma: Improved lung function in phase 2 trials
• Autism: Ongoing trials for behavioral symptoms
• Cognitive function: Early-phase studies in elderly subjects

Safety Profile

Based on prior clinical trials:

• Maximum tolerated dose: Not established; doses of 200 μmol daily have been used
• Common adverse events: GI discomfort at high doses
• Drug interactions: Potential with CYP450 substrates
• Contraindications: Limited; use caution in patients on anticoagulants

Advantages for Neurodegeneration

Trial Design

Objectives

Primary:

• Safety and tolerability of myrosinase-activated glucoraphanin
• Maximum tolerated dose determination
• Pharmacokinetic assessment

• Biomarker modulation (Nrf2 pathway activation)
• Clinical outcome measures
• Dose-response relationships

Inclusion Criteria (Estimated)

• Adults with confirmed neurodegenerative disease diagnosis
• Stable medication regimen
• Age typically 40-80 years
• Ability to provide informed consent

Exclusion Criteria (Estimated)

• Active cancer or recent cancer treatment
• Severe liver or kidney disease
• Pregnancy or breastfeeding
• Concomitant Nrf2-activating supplements

Future Implications

Precision Medicine Applications

This trial may establish:

• Biomarker signatures predicting treatment response
• Optimal dosing for different disease stages
• Combination therapy protocols

Disease-Modifying Potential

If successful, this approach could provide:

• First-line neuroprotective therapy
• Adjunct to existing symptomatic treatments
• Preventive intervention in at-risk populations

Related Pages

• [Glucosinolates and Neuroprotection](/mechanisms/glucosinolate-neuroprotection)
• [Nrf2 Signaling in Neurodegeneration](/mechanisms/nrf2-signaling-neurodegeneration)
• [Sulforaphane Research](/mechanisms/sulforaphane-neuroprotection)
• [Oxidative Stress Mechanisms](/mechanisms/oxidative-stress-neurodegeneration)

External Resources

• [ClinicalTrials.gov NCT07360977](https://clinicaltrials.gov/study/NCT07360977)
• [IRCCS Centro Neurolesi Bonino Pulejo](https://www.centrobonino.it/)
• [PubMed: Sulforaphane neurodegeneration](https://pubmed.ncbi.nlm.nih.gov/?term=sulforaphane+neurodegeneration)

References