Giant axonal neuropathy: studies with sulfhydryl donor compounds

Giant axonal neuropathy (GAN) is a disorder characterized pathologically by distal neurofilament-filled bulbous swellings in axons, and widespread collection of intermediate filaments, including masses of vimentin filaments in cultured skin fibroblasts. A morphologically similar neurofibrillary disorder is produced by acrylamide and the toxic hexacarbons, agents which bind to thiol groups. We report, in GAN fibroblasts, inhibition of vimentin filament aggregation by dithiothreitol and penicillamine, sulfhydryl donor compounds which stabilize thiols. In addition, we describe clinical improvement in a GAN patient treated with penicillamine, despite earlier progressive disease. These findings support the hypothesis of disordered thiol metabolism in GAN, and open up avenues for further research.