Antipsychotic drugs counteract autophagy and mitophagy in multiple sclerosis

Background: Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease characterized by myelin damage followed by axonal and ultimately neuronal loss. The etiology and physiopathology of MS are still elusive, and no fully effective therapy is yet available

Objectives: We investigated the role in MS of autophagy (physiologically, a controlled intracellular pathway regulating the degradation of cellular components) and of mitophagy (a specific form of autophagy that removes dysfunctional mitochondria).

Methods: Our study has been performed by using in vitro, ex vivo and in vivo model of MS. Furthermore, experiments have been also conducted in human biofluids obtained from healthy and MS-affected individuals

Results: Three main findings emerge from the present work. First, autophagy and its selective forms occur in MS patients and in experimental models of MS; second, these phenomena play a causal role in MS be-cause their inhibition prevents myelin loss; third, two clinically used drugs can inhibit autophagy, prevent demyelination, induce remyelination, and revert MS behavioral deficits

Conclusion: Our findings suggest to repurpose Food and Drug Administration–approved drugs for the treatment of MS, at least in patients with MS variants that are more closely modeled by CPZ, like type III and IV. Such compounds may accelerate recovery from a demyelinating attack and prevent relapses.