Neuronopathic disorders

Many of the chaperons used have been imino sugars because of their tight-binding properties to the active site and at sub-inhibitory concentrations produce an enhancement of enzyme that may be sufficient to degrade the lysosomally stored material. For the neuronopathic disorders few candidates have been identified but a recent chemical library screen for potential hexosaminidase chaperons has revealed additional molecular frameworks that could be used that are outside the imino sugar structural motif (Tropak et al., 2007). 

Poor access via the blood-brain barrier is the major obstacle that prevents ERT from being applicable to the neuronopathic disorders. The inflammatory cascade that is mediated by CNS storage seen in the gangliosidoses for example, may respond to steroid treatment but unless the neuronal cell lysosomal burden can be reduced, this peripheral and neurological component of the phenotype could dominate the clinical outcome of disease. 

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