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

De Montfort University Open Research Archive

Show simple item record te Vruchte, Danielle en Speak, Anneliese O. en Wallom, Kerri L. en Al Eisa, Nada en Smith, David A. en Hendriksz, Christian J. en Simmons, Louise en Lachmann, R. H. en Cousins, Alison en Hartang, Ralf en Mengel, Eugen en Runz, Heiko en Beck, Micheal en Amraoui, Yasmina en Imrie, Jackie en Jacklin, Elizabeth en Riddick, Kate en Yanjanin, Nicole M. en Wassif, Christopher A. en Rolfs, Arndt en Rimmele, Florian en Wright, Naomi en Taylor, Clare en Ramaswami, Uma en Cox, Timothy M. en Hastings, Caroline en Jiang, Xuntian en Sidhu, Rohini en Ory, Daniel S. en Arias, Begona en Jeyakumar, Mylvaganam en Sillence, Daniel J. en Wraith, James E. en Porter, Forbes D. en Cortina-Borja, Mario en Platt, Frances M. en 2014-03-28T11:37:50Z 2014-03-28T11:37:50Z 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.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.researchgroup Pharmacology en
dc.peerreviewed Yes en
dc.funder Action Medical Research en
dc.projectid SP4203 and SP3775 en

Files in this item

This item appears in the following Collection(s)

Show simple item record