TY - JOUR
T1 - Mucopolysaccharidosis type I
T2 - Current treatments, limitations and prospects for improvement
AU - Hampe, Christiane S.
AU - Wesley, Jacob
AU - Lund, Troy C.
AU - Orchard, Paul J.
AU - Polgreen, Lynda E.
AU - Eisengart, Julie B.
AU - McLoon, Linda K.
AU - Cureoglu, Sebahattin
AU - Schachern, Patricia
AU - McIvor, R. Scott
N1 - Publisher Copyright:
© 2021 by the authors.
PY - 2021/2
Y1 - 2021/2
N2 - Mucopolysaccharidosis type I (MPS I) is a lysosomal disease, caused by a deficiency of the enzyme alpha-L-iduronidase (IDUA). IDUA catalyzes the degradation of the glycosaminoglycans dermatan and heparan sulfate (DS and HS, respectively). Lack of the enzyme leads to pathologic accumulation of undegraded HS and DS with subsequent disease manifestations in multiple organs. The disease can be divided into severe (Hurler syndrome) and attenuated (Hurler-Scheie, Scheie) forms. Currently approved treatments consist of 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 patients with Hurler syndrome consists of HSCT. While these treatments significantly improve disease manifestations and prolong life, a considerable burden of disease remains. Notably, treatment can partially prevent, but not significantly improve, clinical manifestations, necessitating early diagnosis of disease and commencement of treatment. This review discusses these standard therapies and their impact on common disease manifestations in patients with MPS I. Where relevant, results of animal models of MPS I will be included. Finally, we highlight alternative and emerging treatments for the most common disease manifestations.
AB - Mucopolysaccharidosis type I (MPS I) is a lysosomal disease, caused by a deficiency of the enzyme alpha-L-iduronidase (IDUA). IDUA catalyzes the degradation of the glycosaminoglycans dermatan and heparan sulfate (DS and HS, respectively). Lack of the enzyme leads to pathologic accumulation of undegraded HS and DS with subsequent disease manifestations in multiple organs. The disease can be divided into severe (Hurler syndrome) and attenuated (Hurler-Scheie, Scheie) forms. Currently approved treatments consist of 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 patients with Hurler syndrome consists of HSCT. While these treatments significantly improve disease manifestations and prolong life, a considerable burden of disease remains. Notably, treatment can partially prevent, but not significantly improve, clinical manifestations, necessitating early diagnosis of disease and commencement of treatment. This review discusses these standard therapies and their impact on common disease manifestations in patients with MPS I. Where relevant, results of animal models of MPS I will be included. Finally, we highlight alternative and emerging treatments for the most common disease manifestations.
KW - Animal models
KW - Enzyme replacement therapy
KW - Experimental therapies
KW - Hematopoietic stem cell transplantations
KW - Hurler syndrome
KW - Mucopolysaccharidosis type i
UR - http://www.scopus.com/inward/record.url?scp=85100487068&partnerID=8YFLogxK
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U2 - 10.3390/biom11020189
DO - 10.3390/biom11020189
M3 - Review article
C2 - 33572941
AN - SCOPUS:85100487068
SN - 2218-273X
VL - 11
SP - 1
EP - 25
JO - Biomolecules
JF - Biomolecules
IS - 2
M1 - 189
ER -