@article{85acfad85eee42378ca794fc5c73c7e2,
title = "A phase 1/2 open label nonrandomized clinical trial of intravenous 2-hydroxypropyl-β-cyclodextrin for acute liver disease in infants with Niemann-Pick C1",
abstract = "Introduction: Niemann-Pick C (NPC) is an autosomal recessive disease due to defective NPC1 or NPC2 proteins resulting in endo-lysosomal storage of unesterified cholesterol in the central nervous system and liver. Acute liver disease in the newborn period may be self-limited or fatal. 2-hydroxypropyl-β-cyclodextrin (2HPBCD) is a cholesterol-binding agent that reduces lysosomal cholesterol storage. We have enrolled 3 infants 0–6 months old with direct hyperbilirubinemia due to NPC1 or NPC2 liver disease in a Phase I/II open label clinical trial of intravenous 2HPBCD. Methods: Infants received intravenous 2HPBCD twice a week for 6 weeks, followed by monthly infusion for 6-months. Primary outcome measure was reduction of plasma (3β,5α,6β-trihydroxy-cholan-24-oyl) glycine (TCG), a bile acid generated from cholesterol sequestered in lysosome. Results: Three participants completed this protocol. A fourth patient received intravenous 2HPBCD under an emergency investigational new drug study but later expired from her underlying condition. The three protocol patients are living and have improved liver enzymes and TCG. No patient has experienced a drug-related adverse event. Conclusion: Intravenous 2HPBCD was tolerated in three infants with liver disease due to NPC.",
keywords = "2-hydroxypropyl-β-cyclodextrin (2HPBCD), 3β,5α,6β-trihydroxy-cholan-24-oyl)glycine (TCG), Clinical trial, Cyclodextrin, Niemann Pick C",
author = "Margaret Reynolds and Linneman, {Laura A.} and Sofia Luna and Warner, {Barbara B.} and Turmelle, {Yumirle P.} and Kulkarni, {Sakil S.} and Xuntian Jiang and Geetika Khanna and Marwan Shinawi and Porter, {Forbes D.} and Ory, {Daniel S.} and Cole, {F. Sessions} and Dickson, {Patricia I.}",
note = "Funding Information: Research reported in this publication was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health and the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Number P50 HD103525 to the Intellectual and Developmental Disabilities Research Center at Washington University . The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. Funding Information: The authors wish to acknowledge the support of the I2 WUSM ICS and NCI Cancer Center Support Grant P30 CA091842 , Siteman Comprehensive Cancer Center for supporting the REDCap clinical data capture service as a research resource at WUSM. Funding Information: Funding source is U01 HD090845 , Grants from the National Niemann-Pick Disease Foundation, the NIH CTSA Grant # UL1 TR000448 , Together Strong NPC Foundation, the University of Pennsylvania Orphan Disease Center ( MDBR-17-124-NPC ), the intramural research program of NICHD, NIH . Publisher Copyright: {\textcopyright} 2021",
year = "2021",
month = sep,
doi = "10.1016/j.ymgmr.2021.100772",
language = "English",
volume = "28",
journal = "Molecular Genetics and Metabolism Reports",
issn = "2214-4269",
}