Expanded access with intravenous hydroxypropyl-β-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 en...

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Main Authors: Caroline Hastings, Camilo Vieira, Benny Liu, Cyrus Bascon, Claire Gao, Raymond Y. Wang, Alicia Casey, Sharon Hrynkow
Format: Article
Language:English
Published: BMC 2019-10-01
Series:Orphanet Journal of Rare Diseases
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13023-019-1207-1
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spelling doaj-edff1d73b6a64294a4be6accf53c30032020-11-25T03:40:11ZengBMCOrphanet Journal of Rare Diseases1750-11722019-10-0114111610.1186/s13023-019-1207-1Expanded access with intravenous hydroxypropyl-β-cyclodextrin to treat children and young adults with Niemann-Pick disease type C1: a case report analysisCaroline Hastings0Camilo Vieira1Benny Liu2Cyrus Bascon3Claire Gao4Raymond Y. Wang5Alicia Casey6Sharon Hrynkow7Department of Pediatric Hematology Oncology, UCSF Benioff Children’s Hospital OaklandUniversidade Federal da BahiaGI & Liver Clinics, Highland Hospital, Alameda Health System, Highland HospitalDepartment of Pediatric Hematology Oncology, UCSF Benioff Children’s Hospital OaklandUCSF Benioff Children’s Hospital OaklandDivision of Metabolic Disorders, Children’s Hospital of Orange County, CHOC Children’s SpecialistsBoston Children’s HospitalCTD Holdings, Inc.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 (HPβPD) 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. HPβCD 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 HPβCD in the US and Brazil. Some patients subsequently received intrathecal (IT) treatment with HPβCD following on average 13 months of IV HPβCD. Several patients transitioned to an alternate HPβCD. Moderately affected NPC patients treated with HPβCD 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 HPβCD and provide a platform for two clinical trials to study the effect of intravenous administration of HPβCD in NPC patients.http://link.springer.com/article/10.1186/s13023-019-1207-1Niemann-pick disease type CHydroxypropyl-beta-cyclodextrinIntravenous administrationInvestigational new drug, hepatomegaly, splenomegaly, lung disease
collection DOAJ
language English
format Article
sources DOAJ
author Caroline Hastings
Camilo Vieira
Benny Liu
Cyrus Bascon
Claire Gao
Raymond Y. Wang
Alicia Casey
Sharon Hrynkow
spellingShingle Caroline Hastings
Camilo Vieira
Benny Liu
Cyrus Bascon
Claire Gao
Raymond Y. Wang
Alicia Casey
Sharon Hrynkow
Expanded access with intravenous hydroxypropyl-β-cyclodextrin to treat children and young adults with Niemann-Pick disease type C1: a case report analysis
Orphanet Journal of Rare Diseases
Niemann-pick disease type C
Hydroxypropyl-beta-cyclodextrin
Intravenous administration
Investigational new drug, hepatomegaly, splenomegaly, lung disease
author_facet Caroline Hastings
Camilo Vieira
Benny Liu
Cyrus Bascon
Claire Gao
Raymond Y. Wang
Alicia Casey
Sharon Hrynkow
author_sort Caroline Hastings
title Expanded access with intravenous hydroxypropyl-β-cyclodextrin to treat children and young adults with Niemann-Pick disease type C1: a case report analysis
title_short Expanded access with intravenous hydroxypropyl-β-cyclodextrin to treat children and young adults with Niemann-Pick disease type C1: a case report analysis
title_full Expanded access with intravenous hydroxypropyl-β-cyclodextrin to treat children and young adults with Niemann-Pick disease type C1: a case report analysis
title_fullStr Expanded access with intravenous hydroxypropyl-β-cyclodextrin to treat children and young adults with Niemann-Pick disease type C1: a case report analysis
title_full_unstemmed Expanded access with intravenous hydroxypropyl-β-cyclodextrin to treat children and young adults with Niemann-Pick disease type C1: a case report analysis
title_sort expanded access with intravenous hydroxypropyl-β-cyclodextrin to treat children and young adults with niemann-pick disease type c1: a case report analysis
publisher BMC
series Orphanet Journal of Rare Diseases
issn 1750-1172
publishDate 2019-10-01
description 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 (HPβPD) 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. HPβCD 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 HPβCD in the US and Brazil. Some patients subsequently received intrathecal (IT) treatment with HPβCD following on average 13 months of IV HPβCD. Several patients transitioned to an alternate HPβCD. Moderately affected NPC patients treated with HPβCD 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 HPβCD and provide a platform for two clinical trials to study the effect of intravenous administration of HPβCD in NPC patients.
topic Niemann-pick disease type C
Hydroxypropyl-beta-cyclodextrin
Intravenous administration
Investigational new drug, hepatomegaly, splenomegaly, lung disease
url http://link.springer.com/article/10.1186/s13023-019-1207-1
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