This vision of lysosome biology, however, has dramatically changed in recent years. Since their discovery by Christian de Duve, lysosomes have been viewed as organelles exclusively specialized in degradative functions. The knowledge of the secondary pathways that are implicated in the pathophysiology of MPS is the basis for the development of new treatment strategies that are then discussed. The scope of this article is to review current and new treatment strategies in MPS, with a particular focus on the limitations and challenges imposed by existing therapies with unmet needs. For other pediatric disorders, such as muscular dystrophies, rheumatological diseases, and genetic immunodeficiencies, current research is now focused on the search for “biological” drugs, precisely directed towards specific cellular pathways. The research and the growing expansion of our knowledge in the field of lysosomal storage diseases and MPS represent excellent models of the renewed interest for the biology and the mechanisms of diseases in many other fields of pediatrics. In this respect it is of key importance to understand in detail the cascade of events and the cellular processes that ultimately lead to tissue pathology and clinical manifestations of the MPS. Current research is now trying to address these needs, and to improve the efficacy of existing therapies. Different approaches have been designed to treat these disorders and, for several of them, enzyme replacement therapy (ERT) is currently considered the standard of care however, clinical research is rapidly moving towards other advanced approaches, such as gene therapy.ĭespite considerable success in treating some lysosomal storage diseases, however, current therapies have been unable to cure all the pathological and clinical manifestations of the diseases, leaving several unmet medical needs. Over the past two decades, extraordinary advancements have been achieved in the treatment of lysosomal storage diseases, including the mucopolysaccharidoses (MPS). Some of these pathways may represent novel therapeutic targets and allow for development of novel or adjunctive therapies for these disorders. It is now clear that the clinical manifestations of MPS are not only the direct effects of storage, but also derive from a cascade of secondary events that lead to dysfunction of several cellular processes and pathways. Further innovation will likely be introduced by the recent advancements in the knowledge of lysosomal biology and function. Intrathecal delivery of recombinant enzymes or chimeric enzymes represent promising approaches in this respect. New strategies are currently being tested to address these limitations, in particular to obtain sufficient therapeutic levels in the brain. This approach has shown substantial efficacy mainly on somatic symptoms of the patients, but no benefit was found for other clinical manifestations, such as neurological involvement. Enzyme replacement therapy is currently considered the standard of care for the treatment of mucopolysaccharidoses (MPS) type I, II, VI, and IV.

Mps therapy