5-Aminolevulinic Acid Ameliorates Chronic Experimental Autoimmune Neuritis Through a Dual Mechanism of Mitochondrial Protection and Immunomodulation

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disorder characterized by inflammation and neurodegeneration, yet current therapies lack direct neuroprotective effects. We investigated the therapeutic potential of 5-aminolevulinic acid (5-ALA), a key precursor for mitochondrial heme synthesis, in a chronic experimental autoimmune neuritis (EAN) rat model of CIDP. Rats with established EAN received daily oral 5-ALA (100 mg/kg) or vehicle. Treatment efficacy was assessed by clinical scoring, nerve histopathology, and biochemical analyses of sciatic nerves. 5-ALA administration significantly ameliorated clinical disease severity. This was associated with local immunomodulation in the sciatic nerve, marked by reduced pro-inflammatory IFN-γ and increased anti-inflammatory IL-10 levels. Concurrently, 5-ALA exerted direct neuroprotective effects, evidenced by restored mitochondrial ATP production, decreased oxidative DNA damage, upregulated antioxidant heme oxygenase-1 (HO-1), and improved myelin sheath integrity. These findings suggest that 5-ALA may offer a dual therapeutic benefit by targeting both local inflammation and mitochondrial-mediated neuroprotection. By addressing key pathological mechanisms currently unmet by standard therapies, 5-ALA emerges as a promising disease-modifying candidate for CIDP.