Schwann cell transcript biomarkers for hereditary neuropathy skin biopsies.
Objective: Charcot-Marie-Tooth (CMT) disease is most commonly caused by duplication of a chromosomal segment surrounding Peripheral Myelin Protein 22, or PMP22 gene, which is classified as CMT1A. Several candidate therapies reduce Pmp22 mRNA levels in CMT1A rodent models, but development of biomarke...
| Publicado en: | Annals of Neurology Vol. 85; no. 6; pp. 887 - 899 |
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| Autores principales: | , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Wiley-Blackwell
Jun2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=136420284&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 136420284 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 03645134 1WM jtl: Annals of Neurology issn: 03645134 maglogo: Y pubinfo: dt: Jun2019 vid: 85 iid: 6 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 136420284 136420284 NLM30945774 136420284 10.1002/ana.25480 NLM30945774 136420284 ppf: 887 ppct: 12 formats: tig: atl: Schwann cell transcript biomarkers for hereditary neuropathy skin biopsies. aug: au: Moran, John J. Ramesh, Raghu Svaren, John Wu, Xingyao Bacon, Chelsea Bai, Yunhong Gutmann, Laurie Anderson, Daniel M. Shy, Michael E. Zuccarino, Riccardo Pavelec, Derek affil: Waisman Center, University of Wisconsin‐Madison, Madison WI sug: subj: Peripheral Nerves Pathology Charcot-Marie-Tooth Disease Pathology Skin Pathology Nerve Tissue Proteins Charcot-Marie-Tooth Disease Human Mice Middle Age Adolescence Skin Peripheral Nerves Metabolism Charcot-Marie-Tooth Disease Metabolism Male Biopsy Adult Aged Animal Studies Young Adult Female Validation Studies Comparative Studies Evaluation Research Multicenter Studies Funding Source Middle Aged: 45-64 years Adolescent: 13-18 years Adult: 19-44 years Aged: 65+ years Male Female ab: Objective: Charcot-Marie-Tooth (CMT) disease is most commonly caused by duplication of a chromosomal segment surrounding Peripheral Myelin Protein 22, or PMP22 gene, which is classified as CMT1A. Several candidate therapies reduce Pmp22 mRNA levels in CMT1A rodent models, but development of biomarkers for clinical trials in CMT1A is a challenge given its slow progression and difficulty in obtaining nerve samples. Quantitative PCR measurements of PMP22 mRNA in dermal nerves were performed using skin biopsies in human clinical trials for CMT1A, but this approach did not show increased PMP22 mRNA in CMT1A patients compared to controls. One complicating factor is the variable amounts of Schwann cells (SCs) in skin. The objective of the study was to develop a novel method for precise evaluation of PMP22 levels in skin biopsies that can discriminate CMT1A patients from controls.Methods: We have developed methods to normalize PMP22 transcript levels to SC-specific genes that are not altered by CMT1A status. Several CMT1A-associated genes were assembled into a custom Nanostring panel to enable precise transcript measurements that can be normalized to variable SC content.Results: The digital expression data from Nanostring analysis showed reproducible elevation of PMP22 levels in CMT1A versus control skin biopsies, particularly after normalization to SC-specific genes.Interpretation: This platform should be useful in clinical trials for CMT1A as a biomarker of target engagement that can be used to optimize dosing, and the same normalization framework is applicable to other types of CMT. ANN NEUROL 2019;85:887-898. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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