Dataset Information

Expanded access with intravenous hydroxypropyl-?-cyclodextrin to treat children and young adults with Niemann-Pick disease type C1: a case report analysis.

ABSTRACT: BACKGROUND:Niemann-Pick Disease Type C (NPC) is an inherited, often fatal neurovisceral lysosomal storage disease characterized by cholesterol accumulation in every cell with few known treatments. Defects in cholesterol transport cause sequestration of unesterified cholesterol within the endolysosomal system. The discovery that systemic administration of hydroxypropyl-beta cyclodextrin (HP?PD) to NPC mice could release trapped cholesterol from lysosomes, normalize cholesterol levels in the liver, and prolong life, led to expanded access use in NPC patients. HP?CD has been administered to NPC patients with approved INDs globally since 2009. RESULTS:Here we present safety, tolerability and efficacy data from 12 patients treated intravenously (IV) for over 7?years with HP?CD in the US and Brazil. Some patients subsequently received intrathecal (IT) treatment with HP?CD following on average 13?months of IV HP?CD. Several patients transitioned to an alternate HP?CD. Moderately affected NPC patients treated with HP?CD showed slowing of disease progression. Severely affected patients demonstrated periods of stability but eventually showed progression of disease. Neurologic and neurocognitive benefits were seen in most patients with IV alone, independent of the addition of IT administration. Physicians and caregivers reported improvements in quality of life for the patients on IV therapy. There were no safety issues, and the drug was well tolerated and easy to administer. CONCLUSIONS:These expanded access data support the safety and potential benefit of systemic IV administration of HP?CD and provide a platform for two clinical trials to study the effect of intravenous administration of HP?CD in NPC patients.

SUBMITTER: Hastings C

PROVIDER: S-EPMC6805667 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Expanded access with intravenous hydroxypropyl-β-cyclodextrin to treat children and young adults with Niemann-Pick disease type C1: a case report analysis.

Hastings Caroline C Vieira Camilo C Liu Benny B Bascon Cyrus C Gao Claire C Wang Raymond Y RY Casey Alicia A Hrynkow Sharon S

Orphanet journal of rare diseases 20191021 1

<h4>Background</h4>Niemann-Pick Disease Type C (NPC) is an inherited, often fatal neurovisceral lysosomal storage disease characterized by cholesterol accumulation in every cell with few known treatments. Defects in cholesterol transport cause sequestration of unesterified cholesterol within the endolysosomal system. The discovery that systemic administration of hydroxypropyl-beta cyclodextrin (HPβPD) to NPC mice could release trapped cholesterol from lysosomes, normalize cholesterol levels in t ...[more]

PMID: 31639011

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Project description: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.

Dataset Information

Expanded access with intravenous hydroxypropyl-?-cyclodextrin to treat children and young adults with Niemann-Pick disease type C1: a case report analysis.

Publications

Expanded access with intravenous hydroxypropyl-β-cyclodextrin to treat children and young adults with Niemann-Pick disease type C1: a case report analysis.

Similar Datasets

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