Mucopolysaccharidosis Type I: Current Treatments, Limitations, and Prospects for Improvement
2021-01-29Mucopolysaccharidosis Type I: Current Treatments, Limitations, and Prospects for Improvement
Biomolecules. 2021 Jan 29;11(2):189. doi: 10.3390/biom11020189.
PMID: 33572941
Christiane S Hampe, Jacob Wesley, Troy C Lund, Paul J Orchard, Lynda E Polgreen, Julie B Eisengart, Linda K McLoon, Sebahattin Cureoglu, Patricia Schachern, R Scott McIvor
Summary: There are two types of the Mucopolysaccharidosis type I (MPS I) disease: severe form (Hurler syndrome) and attenuated form (Hurler-Scheie, Scheie). Current treatments can partially prevent, but not significantly improve, clinical manifestations, necessitating early diagnosis of disease and commencement of treatment.
Abstract
Background: Mucopolysaccharidosis type I (MPS I) is a lysosomal disease, caused by a deficiency of the enzyme alpha-L-iduronidase (IDUA). The degradation of glycosaminoglycans dermatan sulfate (DS) and heparan sulfate (HS) are catalyzed by IDUA. In the absence of the enzyme, pathologic accumulation of undegraded HS and DS occurs, resulting in disease manifestations in various organs. There are two types of the disease: severe form (Hurler syndrome) and attenuated form (Hurler-Scheie, Scheie). Currently approved treatments include enzyme replacement therapy (ERT) and/or hematopoietic stem cell transplantation (HSCT). Patients with attenuated disease are often treated with ERT alone, while the recommended therapy for Hurler syndrome is HSCT. Although these medications help to improve disease symptoms and prolong life, there is still a heavy disease burden.
Objective: Notably, treatment can partially prevent, but not significantly improve, clinical manifestations, necessitating early diagnosis of disease and commencement of treatment. These standard therapies and their effect on common disease manifestations in patients with MPS I are discussed in this review. The results of animal models of MPS I will be included where appropriate. Finally, alternative and evolving treatments are highlighted, which are used for the most common disease manifestations.