| 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).
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)
Additional Mechanisms:
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
Sulforaphane is considered an ideal Nrf2 activator because:
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
Blood-brain barrier penetration: Demonstrated in animal models
Multi-target mechanism: Addresses oxidative stress, inflammation, and protein aggregation
Dietary origin: Long history of safe consumption
Scalable production: Can be derived from broccoli seed extract
Trial Design
Objectives
Primary:
Safety and tolerability of myrosinase-activated glucoraphanin
Maximum tolerated dose determination
Pharmacokinetic assessment
Secondary:
Biomarker modulation (Nrf2 pathway activation)
Clinical outcome measures
Dose-response relationships
Inclusion Criteria (Estimated)
Adults with confirmed neurodegenerative disease diagnosis