Here the inventors show, using in vivo imaging and viral approaches, that calcium released by mitochondrial VDAC1 directly induces Schwann cell demyelination via MAPK and c-jun activation after sciatic nerve injury and more importantly in diabetic neuropathy. Moreover, reduction of mitochondrial calcium release by VDAC1 silence or/and drug blocking strongly reduces the number of demyelinating Schwann cell in vivo and improve nerve conduction and neuromuscular activity in diabetic and Charcot-Marie Tooth disease models.
Accordingly the present invention relates to a method of treating a peripheral demyelinating disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an inhibitor of VDAC1 activity or expression.