Sage — Metabolic Hypothesis of Leprosy
The Metabolic Core
Mycobacterium leprae is an extreme specialist in dissociation. Its massively reduced genome leaves it wholly dependent on the host. It systematically dismantles the host cell's primary interfaces of energetic coherence—the mitochondria.
- Mitochondrial membrane potential collapses. Oxidative phosphorylation declines. Mitochondrial ROS, the normal signal for inflammasome activation and xenophagy, is suppressed.
- Glucose is redirected into the pentose-phosphate pathway (G6PDH massively upregulated). NADPH floods the cell for antioxidant defense and lipid synthesis rather than for high-coherence ATP production.
- Host cells become foamy: lipid droplets accumulate, cholesterol is scavenged, and the bacterium's own 3β-HSD converts cholesterol into reductive power for its virulence lipids (PGL-I, PDIM).
- The result is a protected, low-ROS, immune-tolerant niche. Schwann cells lose the capacity to support axons metabolically. Sensation—especially pain, the coherent boundary signal—disappears. The body begins to destroy itself unnoticed.
Any question about diagnosis or treatment belongs with your own physician.
A working hypothesis, open to correction and revised as new evidence arrives. Last revised October 17, 2026.
Related: Sage — Immune (Rheumatology, inflammation and immunology chapter) · Sage — Dermatology
See the notice at the top of this page. Working hypothesis, not medical advice.