Intrathecal 2-hydroxypropyl-beta-cyclodextrin in a single patient with Niemann-Pick C1.
Mol Genet Metab
; 116(1-2): 75-9, 2015.
Article
en En
| MEDLINE
| ID: mdl-26189084
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-ß-cyclodextrin (HP-ß-CD) in a 12-year old subject with mildly symptomatic NPC. The subject received 200mg intrathecal HP-ß-CD administered biweekly via lumbar puncture. To date the subject has received 27 intrathecal HP-ß-CD injections. Intrathecal HP-ß-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-ß-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-ß-CD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inyecciones Espinales
/
Beta-Ciclodextrinas
/
Excipientes
/
Enfermedad de Niemann-Pick Tipo C
Límite:
Child
/
Humans
/
Male
Idioma:
En
Revista:
Mol Genet Metab
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
METABOLISMO
Año:
2015
Tipo del documento:
Article