TY - JOUR
T1 - Hurdles in treating Hurler disease
T2 - Potential routes to achieve a "real" cure
AU - Van Den Broek, Brigitte T.A.
AU - Van Doorn, Jaap
AU - Hegeman, Charlotte V.
AU - Nierkens, Stefan
AU - Lindemans, Caroline A.
AU - Verhoeven-Duif, Nanda
AU - Boelens, Jaap Jan
AU - Van Hasselt, Peter M.
N1 - Publisher Copyright:
© 2020 by The American Society of Hematology.
PY - 2020/6/23
Y1 - 2020/6/23
N2 - Mucopolysaccharidoses (MPSs) are multiorgan devastating diseases for which hematopoietic cell transplantation (HCT) and, to a lesser extent, enzyme replacement therapy have substantially altered the course of the disease. Furthermore, they have resulted in increased overall survival, especially for Hurler disease (MPS-1). However, despite the identification of clinical predictors and harmonized transplantation protocols, disease progression still poses a significant burden to patients, although at a slower pace. To design better therapies, we need to understand why and where current therapies fail. In this review, we discuss important aspects of the underlying disease and the disease progression. We note that the majority of progressive symptoms that occur in "hard-to-treat"tissues are actually tissues that are difficult to reach, such as avascular connective tissue or tissues isolated from the circulation by a specific barrier (eg, blood-brain barrier, blood-retina barrier). Although easily reached tissues are effectively cured by HCT, disease progression is observed in these "hard-to-reach"tissues. We used these insights to critically appraise ongoing experimental endeavors with regard to their potential to overcome the encountered hurdles and improve long-term clinical outcomes in MPS patients treated with HCT.
AB - Mucopolysaccharidoses (MPSs) are multiorgan devastating diseases for which hematopoietic cell transplantation (HCT) and, to a lesser extent, enzyme replacement therapy have substantially altered the course of the disease. Furthermore, they have resulted in increased overall survival, especially for Hurler disease (MPS-1). However, despite the identification of clinical predictors and harmonized transplantation protocols, disease progression still poses a significant burden to patients, although at a slower pace. To design better therapies, we need to understand why and where current therapies fail. In this review, we discuss important aspects of the underlying disease and the disease progression. We note that the majority of progressive symptoms that occur in "hard-to-treat"tissues are actually tissues that are difficult to reach, such as avascular connective tissue or tissues isolated from the circulation by a specific barrier (eg, blood-brain barrier, blood-retina barrier). Although easily reached tissues are effectively cured by HCT, disease progression is observed in these "hard-to-reach"tissues. We used these insights to critically appraise ongoing experimental endeavors with regard to their potential to overcome the encountered hurdles and improve long-term clinical outcomes in MPS patients treated with HCT.
UR - http://www.scopus.com/inward/record.url?scp=85087013847&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2020001708
DO - 10.1182/bloodadvances.2020001708
M3 - Review article
C2 - 32574368
AN - SCOPUS:85087013847
SN - 2473-9529
VL - 4
SP - 2837
EP - 2849
JO - Blood Advances
JF - Blood Advances
IS - 12
ER -