PubTransformer

A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Characterization of hydroxypropyl-beta-cyclodextrins used in the treatment of Niemann-Pick Disease type C1.

Abstract 2-Hydroxypropyl-beta-cyclodextrin (HPβCD) has gained recent attention as a potential therapeutic intervention in the treatment of the rare autosomal-recessive, neurodegenerative lysosomal storage disorder Niemann-Pick Disease Type C1 (NPC1). Notably, HPβCD formulations are not comprised of a single molecular species, but instead are complex mixtures of species with differing degrees of hydroxypropylation of the cyclodextrin ring. The degree of substitution is a critical aspect of the complex mixture as it influences binding to other molecules and thus could potentially modulate biological effects. VTS-270 (Kleptose HPB) and Trappsol® Cyclo™ are HPβCD products under investigation as novel treatments for NPC1. The purpose of the present work is to compare these two different products; analyses were based on ion distribution and abundance profiles using mass spectrometry methodology as a means for assessing key molecular distinctions between products. The method incorporated electrospray ionization and analysis with a linear low-field ion mobility quadrupole time-of-flight instrument. We observed that the number of hydroxypropyl groups (the degrees of substitution) are substantially different between the two products and greater in Trappsol Cyclo than in VTS-270. The principal ions of both samples are ammonium adducts. Isotope clusters for each of the major ions show doubly charged homodimers of the ammonium adducts. In addition, both products show doubly charged homodimers from adduction of both a proton and ammonium. Doubly charged heterodimers are also present, but are more intense in Trappsol Cyclo than in VTS-270. Based on the analytical differences observed between VTS-270 and Trappsol Cyclo with respect to the degree of substitution, the composition and fingerprint of the complex mixture, and the impurity profiles, these products cannot be considered to be the same; the potential biological and clinical implications of these differences are not presently known.
PMID
Related Publications

2-hydroxypropyl-beta-cyclodextrin raises hearing threshold in normal cats and in cats with Niemann-Pick type C disease.

Intracisternal cyclodextrin prevents cerebellar dysfunction and Purkinje cell death in feline Niemann-Pick type C1 disease.

Effects of cyclodextrin in two patients with Niemann-Pick Type C disease.

Collaborative development of 2-hydroxypropyl-β-cyclodextrin for the treatment of Niemann-Pick type C1 disease.

Visual evoked potentials of Niemann-Pick type C1 mice reveal an impairment of the visual pathway that is rescued by 2-hydroxypropyl-ß-cyclodextrin.

Authors

Mayor MeshTerms
Keywords
Journal Title plos one
Publication Year Start




PMID- 28414792
OWN - NLM
STAT- MEDLINE
DA  - 20170417
DCOM- 20170425
LR  - 20170425
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 4
DP  - 2017
TI  - Characterization of hydroxypropyl-beta-cyclodextrins used in the treatment of
      Niemann-Pick Disease type C1.
PG  - e0175478
LID - 10.1371/journal.pone.0175478 [doi]
AB  - 2-Hydroxypropyl-beta-cyclodextrin (HPbetaCD) has gained recent attention as a
      potential therapeutic intervention in the treatment of the rare
      autosomal-recessive, neurodegenerative lysosomal storage disorder Niemann-Pick
      Disease Type C1 (NPC1). Notably, HPbetaCD formulations are not comprised of a
      single molecular species, but instead are complex mixtures of species with
      differing degrees of hydroxypropylation of the cyclodextrin ring. The degree of
      substitution is a critical aspect of the complex mixture as it influences binding
      to other molecules and thus could potentially modulate biological effects.
      VTS-270 (Kleptose HPB) and Trappsol(R) Cyclo are HPbetaCD products under
      investigation as novel treatments for NPC1. The purpose of the present work is to
      compare these two different products; analyses were based on ion distribution and
      abundance profiles using mass spectrometry methodology as a means for assessing
      key molecular distinctions between products. The method incorporated electrospray
      ionization and analysis with a linear low-field ion mobility quadrupole
      time-of-flight instrument. We observed that the number of hydroxypropyl groups
      (the degrees of substitution) are substantially different between the two
      products and greater in Trappsol Cyclo than in VTS-270. The principal ions of
      both samples are ammonium adducts. Isotope clusters for each of the major ions
      show doubly charged homodimers of the ammonium adducts. In addition, both
      products show doubly charged homodimers from adduction of both a proton and
      ammonium. Doubly charged heterodimers are also present, but are more intense in
      Trappsol Cyclo than in VTS-270. Based on the analytical differences observed
      between VTS-270 and Trappsol Cyclo with respect to the degree of substitution,
      the composition and fingerprint of the complex mixture, and the impurity
      profiles, these products cannot be considered to be the same; the potential
      biological and clinical implications of these differences are not presently
      known.
FAU - Yergey, Alfred L
AU  - Yergey AL
AUID- ORCID: http://orcid.org/0000-0002-1233-6981
AD  - Eunice Kennedy Shriver National Institute of Child Health and Human Development, 
      National Institutes of Health, Bethesda, MD, United States of America.
FAU - Blank, Paul S
AU  - Blank PS
AD  - Eunice Kennedy Shriver National Institute of Child Health and Human Development, 
      National Institutes of Health, Bethesda, MD, United States of America.
FAU - Cologna, Stephanie M
AU  - Cologna SM
AD  - Department of Chemistry, University of Illinois at Chicago, Chicago, IL, United
      States of America.
FAU - Backlund, Peter S
AU  - Backlund PS
AD  - Eunice Kennedy Shriver National Institute of Child Health and Human Development, 
      National Institutes of Health, Bethesda, MD, United States of America.
FAU - Porter, Forbes D
AU  - Porter FD
AD  - Eunice Kennedy Shriver National Institute of Child Health and Human Development, 
      National Institutes of Health, Bethesda, MD, United States of America.
FAU - Darling, Allan J
AU  - Darling AJ
AD  - Vtesse, Inc., Gaithersburg, MD, United States of America.
LA  - eng
PT  - Journal Article
DEP - 20170417
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Ammonium Compounds)
RN  - 0 (Ions)
RN  - 0 (beta-Cyclodextrins)
RN  - 94035-02-6 (2-hydroxypropyl-beta-cyclodextrin)
SB  - IM
MH  - Ammonium Compounds/chemistry
MH  - Drug Contamination
MH  - Humans
MH  - Ions/chemistry
MH  - Niemann-Pick Disease, Type C/*drug therapy
MH  - Spectrometry, Mass, Electrospray Ionization/methods
MH  - beta-Cyclodextrins/*chemistry/*therapeutic use
EDAT- 2017/04/18 06:00
MHDA- 2017/04/26 06:00
CRDT- 2017/04/18 06:00
PHST- 2016/10/11 [received]
PHST- 2017/03/27 [accepted]
AID - 10.1371/journal.pone.0175478 [doi]
AID - PONE-D-16-40592 [pii]
PST - epublish
SO  - PLoS One. 2017 Apr 17;12(4):e0175478. doi: 10.1371/journal.pone.0175478.
      eCollection 2017.

<?xml version="1.0" encoding="UTF-8"?>
<b:Sources SelectedStyle="" xmlns:b="http://schemas.openxmlformats.org/officeDocument/2006/bibliography"  xmlns="http://schemas.openxmlformats.org/officeDocument/2006/bibliography" >
</b:Sources>