Abstract
New therapies fundamentally change treatment of lysosomal storage disorders (LSD). For the first time gene therapy led to superior results in two LSDs, metachromatic leukodystrophy and mucopolysaccharidosis type I, both in CNS and in periphery.
Gene therapies are being developed also for other LSDs. Novel therapeutics for enzyme supplementation therapy take advantage of technologies that enable them to cross bloodbrain barrier and enter CNS, unlike the first generation of therapeutic enzymes.
They thus have a potential to treat CNS disease, which can also be targeted by intracerebroventricular infusions of enzymes. Novel pharmacological chaperones and proteostatic modulators can stabilize mutant proteins with residual activity.
Glycolipid synthesis inhibitors can reduce lysosomal storage of glycolipids and alleviate symptoms of LSDs. Combining different modes of therapy may lead to clinical improvements.
For best outcomes it is necessary to perform gene transfer or transplantation of haematopoietic stem cells early, prompting introduction of neonatal screening for LSDs.