Fisetin for ALS
Also known as: 3,3',4',7-Tetrahydroxyflavone
Cellular senescence in ALS motor cortex and spinal cord contributes to non-cell-autonomous motor neuron death.
Mechanism of Action
Fisetin clears senescent astrocytes and microglia that produce neurotoxic SASP factors damaging nearby motor neurons. It activates Nrf2-dependent antioxidant defense and promotes autophagic clearance of protein aggregates.
General mechanism: Bioactive flavonoid. Senolytic (PI3K/Akt/mTOR), Nrf2 activator, GSK3β inhibitor, anti-inflammatory, pro-apoptotic in cancer cells.
Current Evidence
Senescent glial cells identified in ALS spinal cord. Fisetin's senolytic efficacy demonstrated in aged tissues. No ALS-specific trials but mechanistic rationale strong.
Clinical Status: No ALS trials. Senolytic rationale based on ALS pathology research.
Safety Profile
Very safe. Low oral bioavailability. Liposomal formulations being developed. No significant side effects.
Key Research Questions
- Can senolytic therapy reduce non-cell-autonomous motor neuron toxicity in ALS?
- What is the optimal fisetin dosing schedule for ALS senolytic intervention?