Phase I and II clinical trials for the mucopolysaccharidoses

Introduction: The mucopolysaccharidoses are lysosomal diseases characterized by deficient activity of one of the enzymes that degrades glycosaminoglycans. Treatment options are limited; therefore, new treatments are under investigation.Areas covered: We review the medicinal products for the treatment of mucopolysaccharidoses that are currently being investigated in phase I and phase II clinical trials.Expert opinion: The number of alternatives to treat MPS diseases increased dramatically in an attempt to provide therapy options for orphan MPS diseases and to address the unmet needs of the MPS that already have a treatment available. Intravenous enzyme replacement therapy (ERT) with fusion proteins, intrathecal/intracerebroventricular (ICV) ERT and gene therapy are the most promising strategies addressing the CNS manifestations. Stop-codon read-through, although proposed only for patients with nonsense mutations, might be useful in all MPS types. Substrate reduction therapy could also play a role in any MPS type, as anti-inflammatory drugs are also being tested. This new generation of therapies is now in clinical development and should bring new hope to MPS patients. As cost and logistics remain major challenges, especially for low- and middle-income countries, the possibility of having a one-time treatment such as gene therapy is anxiously awaited by affected families and healthcare systems.