Hurdles in treating Hurler disease: Potential routes to achieve a "real" cure Review
| Authors: | van den Broek, B. T. A.; van Doorn, J.; Hegeman, C. V.; Nierkens, S.; Lindemans, C. A.; Verhoeven-Duif, N.; Boelens, J. J.; van Hasselt, P. M. |
| Review Title: | Hurdles in treating Hurler disease: Potential routes to achieve a "real" cure |
| Abstract: | 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. © 2020 by The American Society of Hematology. |
| Keywords: | review; drug safety; apoptosis; protein degradation; inflammation; hematopoietic stem cell transplantation; patient care; blood brain barrier; nanomedicine; ossification; bone remodeling; disease exacerbation; drug delivery system; heparan sulfate; enzyme deficiency; nonviral gene therapy; chaperone; hurler syndrome; genistein; clinical outcome; viral gene therapy; chondroitin sulfate; joint capsule; skeleton malformation; rhodamine b; keratan sulfate; enzyme replacement; priority journal; retina degeneration; mitral valve disease; inverted terminal repeat; mesenchymal stem cell transplantation; dermatan sulfate; autophagy (cellular); aortic valve disease; cornea opacity; focused ultrasound therapy; ligament disease; sleeping beauty transposon; tendon disease |
| Journal Title: | Blood Advances |
| Volume: | 4 |
| Issue: | 12 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2020-06-23 |
| Start Page: | 2837 |
| End Page: | 2849 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2020001708 |
| PUBMED: | 32574368 |
| PROVIDER: | scopus |
| PMCID: | PMC7322951 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 3 August 2020 -- Source: Scopus |
