Leukodystrophies: recent developments in genetics, molecular biology, pathogenesis and treatment

The combined application of recently developed techniques for genetic and b iochemical analysis, neuroimaging and the ability to create animal models h as led to remarkable advances in the field of leukodystrophy research. The present review focuses on recent developments in X-linked adrenoleukodystro phy, Alexanders disease, Canavans disease, metachromatic leukodystrophy, gl oboid cell leukodystrophy (Krabbes disease) and Pelizaeus-Merzbacher diseas e, and briefly discusses new data on six other rare inherited leukodystroph ies. Of the leukodystrophies, 12 can now be diagnosed precisely using nonin vasive techniques, and the molecular defect has been identified in nine of these. Disease incidence can be reduced through genetic counselling. Presym ptomatic diagnosis provides an opportunity for therapeutic intervention. St udy of animal models facilitates elucidation of pathogenic mechanisms and i dentifies pathways that could be targeted by future therapies. Curr Opin Ne urol 14:305-312. (C) 2001 Lippincott Williams & Wilkins.