N-Acetyl Cysteine (NAC) for ALS
Also known as: NAC, Acetylcysteine
NAC replenishes glutathione, the primary intracellular antioxidant depleted in ALS motor neurons.
Mechanism of Action
NAC provides cysteine for glutathione synthesis, directly scavenges ROS, modulates NMDA receptor activity to reduce glutamate excitotoxicity, and activates Nrf2-dependent antioxidant gene expression. It also has anti-inflammatory effects through NF-κB modulation.
General mechanism: Cysteine prodrug for glutathione synthesis. Direct ROS scavenger. NMDA receptor modulator. NF-κB inhibitor.
Current Evidence
Preclinical models show motor neuron protection. Clinical trials in ALS limited and inconclusive. IV NAC may achieve better CNS levels than oral.
Clinical Status: Preclinical. FDA-approved for acetaminophen overdose. Off-label for neurological conditions.
Safety Profile
Very safe. GI effects common with oral use. IV administration well-established (acetaminophen protocol). Rare: bronchospasm in asthmatics.
Key Research Questions
- Can IV NAC achieve therapeutic glutathione levels in the CNS?
- Does NAC reduce oxidative stress biomarkers in ALS patients?