Intrathecal 2-hydroxypropyl-beta-cyclodextrin in a single patient with Niemann-Pick C1

Timothy J. Maarup, Agnes H. Chen, Forbes D. Porter, Nicole Y. Farhat, Daniel S. Ory, Rohini Sidhu, Xuntian Jiang, Patricia I. Dickson

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Niemann-Pick C, type 1 (NPC1) is a progressive autosomal recessive neurologic disease caused by defective intracellular cholesterol and lipid trafficking. There are currently no United States Food and Drug Administration approved treatments for NPC1. We undertook a study evaluating the safety, efficacy, and biomarker response of intrathecal 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) in a 12-year old subject with mildly symptomatic NPC. The subject received 200. mg intrathecal HP-β-CD administered biweekly via lumbar puncture. To date the subject has received 27 intrathecal HP-β-CD injections. Intrathecal HP-β-CD has been generally safe and well tolerated in this subject. There has been an improvement in vertical gaze. The subject has developed subclinical hearing loss at high frequency that is likely HP-β-CD related. Plasma 24-(S)-hydroxycholesterol, a pharmacodynamic biomarker for cholesterol redistribution in the central nervous system, was significantly increased in response to each of the first 5 drug administrations. Further dosing as well as dose escalations are needed to more completely ascertain the safety and efficacy of intrathecal HP-β-CD.

Original languageEnglish
Pages (from-to)75-79
Number of pages5
JournalMolecular genetics and metabolism
Volume116
Issue number1-2
DOIs
StatePublished - Sep 1 2015

Keywords

  • Cyclodextrin
  • Niemann-Pick C
  • Ototoxicity
  • Therapeutic

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