Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy
Cerebral adrenoleukodystrophy (CALD) is a devastating, demyelinating neuroinflammatory manifestation found in up to 40% of young males with an inherited mutation in <i>ABCD1</i>, the causative gene in adrenoleukodystrophy. The search for biomarkers which correlate to CALD disease burden...
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MDPI AG
2022-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/5/913 |
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| author | Hongge Wang Matthew D. Davison Martin L. Kramer Weiliang Qiu Tatiana Gladysheva Ruby M. S. Chiang Can Kayatekin David R. Nascene Leyla A. Taghizadeh Carina J. King Erin E. Nolan Ashish O. Gupta Paul J. Orchard Troy C. Lund |
| author_facet | Hongge Wang Matthew D. Davison Martin L. Kramer Weiliang Qiu Tatiana Gladysheva Ruby M. S. Chiang Can Kayatekin David R. Nascene Leyla A. Taghizadeh Carina J. King Erin E. Nolan Ashish O. Gupta Paul J. Orchard Troy C. Lund |
| author_sort | Hongge Wang |
| collection | DOAJ |
| description | Cerebral adrenoleukodystrophy (CALD) is a devastating, demyelinating neuroinflammatory manifestation found in up to 40% of young males with an inherited mutation in <i>ABCD1</i>, the causative gene in adrenoleukodystrophy. The search for biomarkers which correlate to CALD disease burden and respond to intervention has long been sought after. We used the Olink Proximity Extension Assay (Uppsala, Sweden) to explore the cerebral spinal fluid (CSF) of young males with CALD followed by correlative analysis with plasma. Using the Target 96 Neuro Exploratory panel, we found that, of the five proteins significantly increased in CSF, only neurofilament light chain (NfL) showed a significant correlation between CSF and plasma levels. Young males with CALD had a 11.3-fold increase in plasma NfL compared with controls. Importantly, 9 of 11 young males with CALD who underwent HCT showed a mean decrease in plasma NfL of 50% at 1 year after HCT compared with pre-HCT levels. In conclusion, plasma NfL could be a great value in determining outcomes in CALD and should be scrutinized in future studies in patients prior to CALD development and after therapeutic intervention. |
| first_indexed | 2024-03-09T20:43:30Z |
| format | Article |
| id | doaj.art-34ab98a4720e4380955e7beeeab603d2 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:43:30Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-34ab98a4720e4380955e7beeeab603d22023-11-23T22:52:10ZengMDPI AGCells2073-44092022-03-0111591310.3390/cells11050913Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral AdrenoleukodystrophyHongge Wang0Matthew D. Davison1Martin L. Kramer2Weiliang Qiu3Tatiana Gladysheva4Ruby M. S. Chiang5Can Kayatekin6David R. Nascene7Leyla A. Taghizadeh8Carina J. King9Erin E. Nolan10Ashish O. Gupta11Paul J. Orchard12Troy C. Lund13Translational Sciences, Sanofi Research, Sanofi, Framingham, MA 01701, USATranslational Sciences, Sanofi Research, Sanofi, Framingham, MA 01701, USATranslational Sciences, Sanofi Research, Sanofi, Framingham, MA 01701, USANonclinical Efficacy and Safety, Department of Biostatistics and Programming, Sanofi Development, Sanofi, Framingham, MA 01701, USAIntegrated Drug Discovery, Sanofi Research, Sanofi, Waltham, MA 02451, USARare and Neurological Diseases Research Therapeutic Area, Sanofi, 49 New York Avenue, Framingham, MA 01701, USARare and Neurological Diseases Research Therapeutic Area, Sanofi, 49 New York Avenue, Framingham, MA 01701, USADepartment of Diagnostic Radiology, University of Minnesota Medical Center, Minneapolis, MN 55455, USADivision of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USADivision of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USADivision of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USADivision of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USADivision of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USADivision of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USACerebral adrenoleukodystrophy (CALD) is a devastating, demyelinating neuroinflammatory manifestation found in up to 40% of young males with an inherited mutation in <i>ABCD1</i>, the causative gene in adrenoleukodystrophy. The search for biomarkers which correlate to CALD disease burden and respond to intervention has long been sought after. We used the Olink Proximity Extension Assay (Uppsala, Sweden) to explore the cerebral spinal fluid (CSF) of young males with CALD followed by correlative analysis with plasma. Using the Target 96 Neuro Exploratory panel, we found that, of the five proteins significantly increased in CSF, only neurofilament light chain (NfL) showed a significant correlation between CSF and plasma levels. Young males with CALD had a 11.3-fold increase in plasma NfL compared with controls. Importantly, 9 of 11 young males with CALD who underwent HCT showed a mean decrease in plasma NfL of 50% at 1 year after HCT compared with pre-HCT levels. In conclusion, plasma NfL could be a great value in determining outcomes in CALD and should be scrutinized in future studies in patients prior to CALD development and after therapeutic intervention.https://www.mdpi.com/2073-4409/11/5/913adrenoleukodystrophybiomarkersneurofilament light chain |
| spellingShingle | Hongge Wang Matthew D. Davison Martin L. Kramer Weiliang Qiu Tatiana Gladysheva Ruby M. S. Chiang Can Kayatekin David R. Nascene Leyla A. Taghizadeh Carina J. King Erin E. Nolan Ashish O. Gupta Paul J. Orchard Troy C. Lund Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy Cells adrenoleukodystrophy biomarkers neurofilament light chain |
| title | Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy |
| title_full | Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy |
| title_fullStr | Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy |
| title_full_unstemmed | Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy |
| title_short | Evaluation of Neurofilament Light Chain as a Biomarker of Neurodegeneration in X-Linked Childhood Cerebral Adrenoleukodystrophy |
| title_sort | evaluation of neurofilament light chain as a biomarker of neurodegeneration in x linked childhood cerebral adrenoleukodystrophy |
| topic | adrenoleukodystrophy biomarkers neurofilament light chain |
| url | https://www.mdpi.com/2073-4409/11/5/913 |
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