Relative acidic compartment volume as a lysosomal storage disorder–associated biomarker

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dc.contributor.author te Vruchte, Danielle en
dc.contributor.author Speak, Anneliese O. en
dc.contributor.author Wallom, Kerri L. en
dc.contributor.author Al Eisa, Nada en
dc.contributor.author Smith, David A. en
dc.contributor.author Hendriksz, Christian J. en
dc.contributor.author Simmons, Louise en
dc.contributor.author Lachmann, R. H. en
dc.contributor.author Cousins, Alison en
dc.contributor.author Hartang, Ralf en
dc.contributor.author Mengel, Eugen en
dc.contributor.author Runz, Heiko en
dc.contributor.author Beck, Micheal en
dc.contributor.author Amraoui, Yasmina en
dc.contributor.author Imrie, Jackie en
dc.contributor.author Jacklin, Elizabeth en
dc.contributor.author Riddick, Kate en
dc.contributor.author Yanjanin, Nicole M. en
dc.contributor.author Wassif, Christopher A. en
dc.contributor.author Rolfs, Arndt en
dc.contributor.author Rimmele, Florian en
dc.contributor.author Wright, Naomi en
dc.contributor.author Taylor, Clare en
dc.contributor.author Ramaswami, Uma en
dc.contributor.author Cox, Timothy M. en
dc.contributor.author Hastings, Caroline en
dc.contributor.author Jiang, Xuntian en
dc.contributor.author Sidhu, Rohini en
dc.contributor.author Ory, Daniel S. en
dc.contributor.author Arias, Begona en
dc.contributor.author Jeyakumar, Mylvaganam en
dc.contributor.author Sillence, Daniel J. en
dc.contributor.author Wraith, James E. en
dc.contributor.author Porter, Forbes D. en
dc.contributor.author Cortina-Borja, Mario en
dc.contributor.author Platt, Frances M. en
dc.date.accessioned 2014-03-28T11:37:50Z
dc.date.available 2014-03-28T11:37:50Z
dc.date.issued 2014-03-03
dc.identifier.citation te Vruchte, D. et al. (2014) Relative acidic compartment volume as a lysosomal storage disorder–associated biomarker. Journal of Clinical Investigation, 124 (3), pp. 1320–1328 en
dc.identifier.uri http://hdl.handle.net/2086/9855
dc.description.abstract Lysosomal storage disorders (LSDs) occur at a frequency of 1 in every 5,000 live births and are a common cause of pediatric neurodegenerative disease. The relatively small number of patients with LSDs and lack of validated biomarkers are substantial challenges for clinical trial design. Here, we evaluated the use of a commercially available fluorescent probe, Lysotracker, that can be used to measure the relative acidic compartment volume of circulating B cells as a potentially universal biomarker for LSDs. We validated this metric in a mouse model of the LSD Niemann-Pick type C1 disease (NPC1) and in a prospective 5-year international study of NPC patients. Pediatric NPC subjects had elevated acidic compartment volume that correlated with age-adjusted clinical severity and was reduced in response to therapy with miglustat, a European Medicines Agency–approved drug that has been shown to reduce NPC1-associated neuropathology. Measurement of relative acidic compartment volume was also useful for monitoring therapeutic responses of an NPC2 patient after bone marrow transplantation. Furthermore, this metric identified a potential adverse event in NPC1 patients receiving i.v. cyclodextrin therapy. Our data indicate that relative acidic compartment volume may be a useful biomarker to aid diagnosis, clinical monitoring, and evaluation of therapeutic responses in patients with lysosomal disorders. en
dc.language.iso en en
dc.subject Niemann-Pick C en
dc.subject Lysosome en
dc.subject Lysotracker en
dc.subject Lysosomal storage disease en
dc.subject Glycolipid en
dc.title Relative acidic compartment volume as a lysosomal storage disorder–associated biomarker en
dc.type Article en
dc.identifier.doi http://dx.doi.org/10.1172/JCI72835
dc.researchgroup Pharmacology en
dc.peerreviewed Yes en
dc.funder Action Medical Research en
dc.projectid SP4203 and SP3775 en


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