Clinical Trial Identifier: NCT07360977
| 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 |
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.
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
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
Neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and ALS 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).
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
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
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
In MPTP and 6-OHDA models:
- Protected dopaminergic neurons from toxicity
- Reduced behavioral deficits
- Decreased α-synuclein aggregation
- Improved mitochondrial function
In SOD1 transgenic mice:
- Delayed disease onset
- Extended survival
- Reduced motor neuron degeneration
- Decreased oxidative stress markers
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
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
- 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
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
- Adults with confirmed neurodegenerative disease diagnosis
- Stable medication regimen
- Age typically 40-80 years
- Ability to provide informed consent
- Active cancer or recent cancer treatment
- Severe liver or kidney disease
- Pregnancy or breastfeeding
- Concomitant Nrf2-activating supplements
This trial may establish:
- Biomarker signatures predicting treatment response
- Optimal dosing for different disease stages
- Combination therapy protocols
If successful, this approach could provide:
- First-line neuroprotective therapy
- Adjunct to existing symptomatic treatments
- Preventive intervention in at-risk populations