Treating the Brain: The Model of MLD

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder, based on the enzyme deficiency of arylsulfatase A. This results in accumulation of sulfatides predominantly in the white matter of the central and peripheral nervous system, leading to demyelination and progressive neurological deterioration. Although no curative treatment has been established yet, promising therapeutic approaches exist, partly still in clinical trials. Both genetically modified as well as donor-derived hematopoietic stem cells aim to provide endogenous, enzyme replacement therapy exogenous replacement of the deficient enzyme. Besides the access to the brain, the main challenge consists of the therapeutic evaluation in this rare disease. In this regard, natural course data and standardized parameters for disease progression are essential. Current studies have shown that early therapy is important for treatment success. Prognostic factors from baseline parameters of recent studies may help in defining inclusion criteria for treatment.