Cargando…

Magnetic resonance brain volumetry biomarkers of CLN2 Batten disease identified with miniswine model

Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease (Batten disease) is a rare pediatric disease, with symptom development leading to clinical diagnosis. Early diagnosis and effective tracking of disease progression are required for treatment. We hypothesize that brain volumetry is v...

Descripción completa

Detalles Bibliográficos
Autores principales: Knoernschild, Kevin, Johnson, Hans J., Schroeder, Kimberly E., Swier, Vicki J., White, Katherine A., Sato, Takashi S., Rogers, Christopher S., Weimer, Jill M., Sieren, Jessica C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060411/
https://www.ncbi.nlm.nih.gov/pubmed/36991106
http://dx.doi.org/10.1038/s41598-023-32071-z
_version_ 1785017091156344832
author Knoernschild, Kevin
Johnson, Hans J.
Schroeder, Kimberly E.
Swier, Vicki J.
White, Katherine A.
Sato, Takashi S.
Rogers, Christopher S.
Weimer, Jill M.
Sieren, Jessica C.
author_facet Knoernschild, Kevin
Johnson, Hans J.
Schroeder, Kimberly E.
Swier, Vicki J.
White, Katherine A.
Sato, Takashi S.
Rogers, Christopher S.
Weimer, Jill M.
Sieren, Jessica C.
author_sort Knoernschild, Kevin
collection PubMed
description Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease (Batten disease) is a rare pediatric disease, with symptom development leading to clinical diagnosis. Early diagnosis and effective tracking of disease progression are required for treatment. We hypothesize that brain volumetry is valuable in identifying CLN2 disease at an early stage and tracking disease progression in a genetically modified miniswine model. CLN2(R208X/R208X) miniswine and wild type controls were evaluated at 12- and 17-months of age, correlating to early and late stages of disease progression. Magnetic resonance imaging (MRI) T1- and T2-weighted data were acquired. Total intercranial, gray matter, cerebrospinal fluid, white matter, caudate, putamen, and ventricle volumes were calculated and expressed as proportions of the intracranial volume. The brain regions were compared between timepoints and cohorts using Gardner-Altman plots, mean differences, and confidence intervals. At an early stage of disease, the total intracranial volume (− 9.06 cm(3)), gray matter (− 4.37% 95 CI − 7.41; − 1.83), caudate (− 0.16%, 95 CI − 0.24; − 0.08) and putamen (− 0.11% 95 CI − 0.23; − 0.02) were all notably smaller in CLN2(R208X/R208X) miniswines versus WT, while cerebrospinal fluid was larger (+ 3.42%, 95 CI 2.54; 6.18). As the disease progressed to a later stage, the difference between the gray matter (− 8.27%, 95 CI − 10.1; − 5.56) and cerebrospinal fluid (+ 6.88%, 95 CI 4.31; 8.51) continued to become more pronounced, while others remained stable. MRI brain volumetry in this miniswine model of CLN2 disease is sensitive to early disease detection and longitudinal change monitoring, providing a valuable tool for pre-clinical treatment development and evaluation.
format Online
Article
Text
id pubmed-10060411
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-100604112023-03-31 Magnetic resonance brain volumetry biomarkers of CLN2 Batten disease identified with miniswine model Knoernschild, Kevin Johnson, Hans J. Schroeder, Kimberly E. Swier, Vicki J. White, Katherine A. Sato, Takashi S. Rogers, Christopher S. Weimer, Jill M. Sieren, Jessica C. Sci Rep Article Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease (Batten disease) is a rare pediatric disease, with symptom development leading to clinical diagnosis. Early diagnosis and effective tracking of disease progression are required for treatment. We hypothesize that brain volumetry is valuable in identifying CLN2 disease at an early stage and tracking disease progression in a genetically modified miniswine model. CLN2(R208X/R208X) miniswine and wild type controls were evaluated at 12- and 17-months of age, correlating to early and late stages of disease progression. Magnetic resonance imaging (MRI) T1- and T2-weighted data were acquired. Total intercranial, gray matter, cerebrospinal fluid, white matter, caudate, putamen, and ventricle volumes were calculated and expressed as proportions of the intracranial volume. The brain regions were compared between timepoints and cohorts using Gardner-Altman plots, mean differences, and confidence intervals. At an early stage of disease, the total intracranial volume (− 9.06 cm(3)), gray matter (− 4.37% 95 CI − 7.41; − 1.83), caudate (− 0.16%, 95 CI − 0.24; − 0.08) and putamen (− 0.11% 95 CI − 0.23; − 0.02) were all notably smaller in CLN2(R208X/R208X) miniswines versus WT, while cerebrospinal fluid was larger (+ 3.42%, 95 CI 2.54; 6.18). As the disease progressed to a later stage, the difference between the gray matter (− 8.27%, 95 CI − 10.1; − 5.56) and cerebrospinal fluid (+ 6.88%, 95 CI 4.31; 8.51) continued to become more pronounced, while others remained stable. MRI brain volumetry in this miniswine model of CLN2 disease is sensitive to early disease detection and longitudinal change monitoring, providing a valuable tool for pre-clinical treatment development and evaluation. Nature Publishing Group UK 2023-03-29 /pmc/articles/PMC10060411/ /pubmed/36991106 http://dx.doi.org/10.1038/s41598-023-32071-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Knoernschild, Kevin
Johnson, Hans J.
Schroeder, Kimberly E.
Swier, Vicki J.
White, Katherine A.
Sato, Takashi S.
Rogers, Christopher S.
Weimer, Jill M.
Sieren, Jessica C.
Magnetic resonance brain volumetry biomarkers of CLN2 Batten disease identified with miniswine model
title Magnetic resonance brain volumetry biomarkers of CLN2 Batten disease identified with miniswine model
title_full Magnetic resonance brain volumetry biomarkers of CLN2 Batten disease identified with miniswine model
title_fullStr Magnetic resonance brain volumetry biomarkers of CLN2 Batten disease identified with miniswine model
title_full_unstemmed Magnetic resonance brain volumetry biomarkers of CLN2 Batten disease identified with miniswine model
title_short Magnetic resonance brain volumetry biomarkers of CLN2 Batten disease identified with miniswine model
title_sort magnetic resonance brain volumetry biomarkers of cln2 batten disease identified with miniswine model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060411/
https://www.ncbi.nlm.nih.gov/pubmed/36991106
http://dx.doi.org/10.1038/s41598-023-32071-z
work_keys_str_mv AT knoernschildkevin magneticresonancebrainvolumetrybiomarkersofcln2battendiseaseidentifiedwithminiswinemodel
AT johnsonhansj magneticresonancebrainvolumetrybiomarkersofcln2battendiseaseidentifiedwithminiswinemodel
AT schroederkimberlye magneticresonancebrainvolumetrybiomarkersofcln2battendiseaseidentifiedwithminiswinemodel
AT swiervickij magneticresonancebrainvolumetrybiomarkersofcln2battendiseaseidentifiedwithminiswinemodel
AT whitekatherinea magneticresonancebrainvolumetrybiomarkersofcln2battendiseaseidentifiedwithminiswinemodel
AT satotakashis magneticresonancebrainvolumetrybiomarkersofcln2battendiseaseidentifiedwithminiswinemodel
AT rogerschristophers magneticresonancebrainvolumetrybiomarkersofcln2battendiseaseidentifiedwithminiswinemodel
AT weimerjillm magneticresonancebrainvolumetrybiomarkersofcln2battendiseaseidentifiedwithminiswinemodel
AT sierenjessicac magneticresonancebrainvolumetrybiomarkersofcln2battendiseaseidentifiedwithminiswinemodel