Utility of 24(S)-hydroxycholesterol as a proximal biomarker to monitor long-term intrathecal adrabetadex therapy in individuals with Niemann-Pick disease, type C1

Forbes D. Porter; Derek M. Alexander; Orsolya K. Albert; Kendall P. Robbins; Desiree A. Labor; Aiden J. Borruso; Nicole Y. Farhat; Xuntian Jiang; Elizabeth Berry-Kravis

doi:10.1016/j.ymgme.2025.109254

Utility of 24(S)-hydroxycholesterol as a proximal biomarker to monitor long-term intrathecal adrabetadex therapy in individuals with Niemann-Pick disease, type C1

Forbes D. Porter
, Derek M. Alexander
, Orsolya K. Albert
, Kendall P. Robbins
, Desiree A. Labor
, Aiden J. Borruso
, Nicole Y. Farhat
, Xuntian Jiang
, Elizabeth Berry-Kravis

Research output: Contribution to journal › Article › peer-review

Abstract

Niemann-Pick disease, type C1 (NPC1) is a lysosomal disease characterized by endolysosomal storage of unesterified cholesterol. Individuals with NPC1 manifest progressive neurodegeneration. Identification and characterization of proximal biomarkers is essential for developing therapeutic interventions. Increased levels of 24(S)-hydroxycholesterol (24(S)OHC) after intrathecal administration of adrabetadex reflect correction of the biochemical defect in neurons. In this study, we show that 24(S)OHC remains a robust proximal biomarker in individuals treated with IT adrabetadex for over four years.

Original language	English
Article number	109254
Journal	Molecular genetics and metabolism
Volume	146
Issue number	4
DOIs	https://doi.org/10.1016/j.ymgme.2025.109254
State	Published - Dec 2025

Keywords

2-hydroxypropyl-B-cyclodextrin
24(S)-hydroxycholesterol
Adrabetadex
NPC1
Niemann-Pick disease, type C1
Proximal Biomarker

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10.1016/j.ymgme.2025.109254

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Porter, F. D., Alexander, D. M., Albert, O. K., Robbins, K. P., Labor, D. A., Borruso, A. J., Farhat, N. Y., Jiang, X., & Berry-Kravis, E. (2025). Utility of 24(S)-hydroxycholesterol as a proximal biomarker to monitor long-term intrathecal adrabetadex therapy in individuals with Niemann-Pick disease, type C1. Molecular genetics and metabolism, 146(4), Article 109254. https://doi.org/10.1016/j.ymgme.2025.109254

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title = "Utility of 24(S)-hydroxycholesterol as a proximal biomarker to monitor long-term intrathecal adrabetadex therapy in individuals with Niemann-Pick disease, type C1",

abstract = "Niemann-Pick disease, type C1 (NPC1) is a lysosomal disease characterized by endolysosomal storage of unesterified cholesterol. Individuals with NPC1 manifest progressive neurodegeneration. Identification and characterization of proximal biomarkers is essential for developing therapeutic interventions. Increased levels of 24(S)-hydroxycholesterol (24(S)OHC) after intrathecal administration of adrabetadex reflect correction of the biochemical defect in neurons. In this study, we show that 24(S)OHC remains a robust proximal biomarker in individuals treated with IT adrabetadex for over four years.",

keywords = "2-hydroxypropyl-B-cyclodextrin, 24(S)-hydroxycholesterol, Adrabetadex, NPC1, Niemann-Pick disease, type C1, Proximal Biomarker",

author = "Porter, \{Forbes D.\} and Alexander, \{Derek M.\} and Albert, \{Orsolya K.\} and Robbins, \{Kendall P.\} and Labor, \{Desiree A.\} and Borruso, \{Aiden J.\} and Farhat, \{Nicole Y.\} and Xuntian Jiang and Elizabeth Berry-Kravis",

note = "Publisher Copyright: {\^A}{\textcopyright} 2025 Published by Elsevier Inc.",

year = "2025",

month = dec,

doi = "10.1016/j.ymgme.2025.109254",

language = "English",

volume = "146",

journal = "Molecular genetics and metabolism",

issn = "1096-7192",

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Porter, FD, Alexander, DM, Albert, OK, Robbins, KP, Labor, DA, Borruso, AJ, Farhat, NY, Jiang, X & Berry-Kravis, E 2025, 'Utility of 24(S)-hydroxycholesterol as a proximal biomarker to monitor long-term intrathecal adrabetadex therapy in individuals with Niemann-Pick disease, type C1', Molecular genetics and metabolism, vol. 146, no. 4, 109254. https://doi.org/10.1016/j.ymgme.2025.109254

Utility of 24(S)-hydroxycholesterol as a proximal biomarker to monitor long-term intrathecal adrabetadex therapy in individuals with Niemann-Pick disease, type C1. / Porter, Forbes D.; Alexander, Derek M.; Albert, Orsolya K. et al.
In: Molecular genetics and metabolism, Vol. 146, No. 4, 109254, 12.2025.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Utility of 24(S)-hydroxycholesterol as a proximal biomarker to monitor long-term intrathecal adrabetadex therapy in individuals with Niemann-Pick disease, type C1

AU - Porter, Forbes D.

AU - Alexander, Derek M.

AU - Albert, Orsolya K.

AU - Robbins, Kendall P.

AU - Labor, Desiree A.

AU - Borruso, Aiden J.

AU - Farhat, Nicole Y.

AU - Jiang, Xuntian

AU - Berry-Kravis, Elizabeth

PY - 2025/12

Y1 - 2025/12

N2 - Niemann-Pick disease, type C1 (NPC1) is a lysosomal disease characterized by endolysosomal storage of unesterified cholesterol. Individuals with NPC1 manifest progressive neurodegeneration. Identification and characterization of proximal biomarkers is essential for developing therapeutic interventions. Increased levels of 24(S)-hydroxycholesterol (24(S)OHC) after intrathecal administration of adrabetadex reflect correction of the biochemical defect in neurons. In this study, we show that 24(S)OHC remains a robust proximal biomarker in individuals treated with IT adrabetadex for over four years.

AB - Niemann-Pick disease, type C1 (NPC1) is a lysosomal disease characterized by endolysosomal storage of unesterified cholesterol. Individuals with NPC1 manifest progressive neurodegeneration. Identification and characterization of proximal biomarkers is essential for developing therapeutic interventions. Increased levels of 24(S)-hydroxycholesterol (24(S)OHC) after intrathecal administration of adrabetadex reflect correction of the biochemical defect in neurons. In this study, we show that 24(S)OHC remains a robust proximal biomarker in individuals treated with IT adrabetadex for over four years.

KW - 2-hydroxypropyl-B-cyclodextrin

KW - 24(S)-hydroxycholesterol

KW - Adrabetadex

KW - NPC1

KW - Niemann-Pick disease, type C1

KW - Proximal Biomarker

UR - https://www.scopus.com/pages/publications/105024431186

U2 - 10.1016/j.ymgme.2025.109254

DO - 10.1016/j.ymgme.2025.109254

M3 - Article

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AN - SCOPUS:105024431186

SN - 1096-7192

VL - 146

JO - Molecular genetics and metabolism

JF - Molecular genetics and metabolism

IS - 4

M1 - 109254

ER -

Utility of 24(S)-hydroxycholesterol as a proximal biomarker to monitor long-term intrathecal adrabetadex therapy in individuals with Niemann-Pick disease, type C1

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