Hematopoietic Stem Cell Therapy and Novel Approaches for Mucopolysaccharidoses

Mucopolysaccharidoses (MPS) are a group of inherited genetic linked enzyme deficiency lysosomal storage disorders. The deficiency of the enzymeis caused by a gene mutation that leads to the accumulation of harmful Glycosaminoglycans (GAGs) in the cells, tissues and blood. Disease-mutation leads to abnormal accumulation of GAGs: Dermatan Sulfate (DS), Heparan Sulfate (HS), chondroitin sulfate, and keratan sulfate resulting in clinical manifestations of varying severity. Recent advances have shown abnormal HS involvement in Central Nervous System (CNS) dysfunction. Therapeutic options vary according to the type of MPS. In severe MPS I patients, the best therapeutic approach is Hematopoietic Stem Cell Transplantation (HSCT). Unlike in other MPS, when it is performed in MPS I patients, HSCT has the ability to continuously produce the deficient enzyme that crosses the blood-brain barrier, a useful effect for CNS defects and in fine for mitigating cognitive and developmental delays. Pharmacological options include Enzyme Replacement Therapy (ERT). Three recombinant human enzymes have so far been approved by the US Food and Drug Administration (FDA) for the treatment of MPS: laronidase for MPS I, idursulfase for MPS II, and galsulfase for MPS VI. However, some of the results of ERT are still controversial. Finally, novel therapeutic avenues (i.e., substrate reduction therapy) have been recently proposed. We review here the different therapeutic approaches proposed in MPS, focusing on MPS I, the MPS that is benefiting most from HSCT so far.