Schwann cell transcript biomarkers for hereditary neuropathy skin biopsies.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
22
01
2019
revised:
02
04
2019
accepted:
03
04
2019
pubmed:
5
4
2019
medline:
31
3
2020
entrez:
5
4
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 30945774
doi: 10.1002/ana.25480
pmc: PMC7050273
mid: NIHMS1560473
doi:
Substances chimiques
Biomarkers
0
Myelin Proteins
0
PMP22 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
887-898Subventions
Organisme : NCATS NIH HHS
ID : R21 TR003034
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD090256
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS065712
Pays : United States
Organisme : Charcot-Marie-Tooth Association
Pays : International
Informations de copyright
© 2019 American Neurological Association.
Références
Neurology. 2015 Jan 27;84(4):407-14
pubmed: 25540311
Neuromuscul Disord. 2015 Oct;25(10):786-93
pubmed: 26227883
Brain. 2009 Dec;132(Pt 12):3263-73
pubmed: 19923170
Neurology. 2015 Jul 21;85(3):228-34
pubmed: 26109717
Hum Mutat. 2016 Jan;37(1):98-109
pubmed: 26486801
BMC Bioinformatics. 2011 Aug 04;12:323
pubmed: 21816040
Cell Rep. 2017 Sep 12;20(11):2719-2734
pubmed: 28903050
Brain. 2000 Jul;123 ( Pt 7):1516-27
pubmed: 10869062
Neuron. 2017 Sep 27;96(1):98-114.e7
pubmed: 28957681
Glia. 2018 Nov;66(11):2487-2502
pubmed: 30306639
Neurology. 2015 Oct 6;85(14):1202-8
pubmed: 26362287
Neuron Glia Biol. 2007 Nov;3(4):377-87
pubmed: 18634568
Dev Cell. 2015 Sep 14;34(5):577-91
pubmed: 26256211
Nucleic Acids Res. 2012 Aug;40(14):6449-60
pubmed: 22492709
J Clin Invest. 2009 Jun;119(6):1714-26
pubmed: 19451695
Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8998-9003
pubmed: 12084938
Brain. 2012 Jan;135(Pt 1):72-87
pubmed: 22189569
Glia. 2012 May;60(5):751-60
pubmed: 22337502
Ann Clin Transl Neurol. 2017 Jun 15;4(8):601-607
pubmed: 28812050
Methods Mol Biol. 2016;1418:391-416
pubmed: 27008025
BMC Bioinformatics. 2014 Jun 12;15:182
pubmed: 24925680
Brain. 2007 Oct;130(Pt 10):2703-14
pubmed: 17898011
Brain. 2011 Sep;134(Pt 9):2664-76
pubmed: 21840889
Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2596-601
pubmed: 15695336
Neurology. 2018 Sep 18;91(12):e1125-e1129
pubmed: 30120135
Bioinformatics. 2003 Feb 12;19(3):368-75
pubmed: 12584122
Lancet Neurol. 2016 Jan;15(1):65-77
pubmed: 26549782
Nat Protoc. 2013 Sep;8(9):1765-86
pubmed: 23975260
Nat Commun. 2018 Aug 2;9(1):3025
pubmed: 30072689
J Peripher Nerv Syst. 2014 Sep;19(3):192-6
pubmed: 25400013
J Neurosci. 2006 Sep 20;26(38):9771-9
pubmed: 16988048
Nat Protoc. 2008;3(6):1101-8
pubmed: 18546601
Neuron. 2010 Feb 25;65(4):490-502
pubmed: 20188654
Orphanet J Rare Dis. 2014 Dec 10;9:201
pubmed: 25491744
Nat Med. 2003 Dec;9(12):1533-7
pubmed: 14608378
Brain. 2018 Dec 1;141(12):3319-3330
pubmed: 30476010
Neuron. 2012 Aug 23;75(4):633-47
pubmed: 22920255
J Neurol Neurosurg Psychiatry. 2017 Nov;88(11):941-952
pubmed: 28860329
Nat Genet. 2013 Jun;45(6):580-5
pubmed: 23715323
Hum Mol Genet. 1998 Mar;7(3):449-58
pubmed: 9467003
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
BMC Med Genomics. 2015 Aug 22;8:54
pubmed: 26297356
J Neurochem. 2006 Mar;96(5):1441-57
pubmed: 16478531
Methods. 2013 Jan;59(1):101-7
pubmed: 22926236
Hum Mol Genet. 1999 Jul;8(7):1245-51
pubmed: 10369870
Neurology. 2018 Feb 6;90(6):e518-e524
pubmed: 29321234
Brain. 2014 Jun;137(Pt 6):1614-20
pubmed: 24812204
Clin Chem. 2015 Nov;61(11):1343-53
pubmed: 26408531
Glia. 2014 May;62(5):736-50
pubmed: 24526449
Cancer Res. 2015 Jul 1;75(13):2587-93
pubmed: 26069246
Brain Behav Immun. 2010 Nov;24(8):1254-67
pubmed: 20688153
J Neurosci. 2014 Apr 9;34(15):5089-98
pubmed: 24719088
Orphanet J Rare Dis. 2014 Dec 18;9:199
pubmed: 25519680
Glia. 2015 Nov;63(11):1897-1914
pubmed: 25974668
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
BMC Bioinformatics. 2007 Apr 20;8:131
pubmed: 17445280
Lancet Neurol. 2011 Apr;10(4):320-8
pubmed: 21393063
Neurobiol Dis. 2005 Apr;18(3):656-68
pubmed: 15755691
Brain. 2009 Jul;132(Pt 7):1734-40
pubmed: 19447823
J Peripher Nerv Syst. 2011 Dec;16(4):295-303
pubmed: 22176144
Nat Biotechnol. 2008 Mar;26(3):317-25
pubmed: 18278033
J Clin Invest. 2018 Jan 2;128(1):359-368
pubmed: 29202483
J Biol Chem. 1994 Oct 14;269(41):25795-808
pubmed: 7929285
J Dermatol Sci. 2012 Mar;65(3):162-9
pubmed: 22305014
Brain. 2005 May;128(Pt 5):1168-77
pubmed: 15774502
Brain. 2014 Nov;137(Pt 11):2922-37
pubmed: 25216747
Proc Natl Acad Sci U S A. 1986 Jun;83(11):4094-8
pubmed: 3012551
Biol Chem. 2013 Dec;394(12):1583-93
pubmed: 23729567
JAMA Neurol. 2013 Aug;70(8):981-7
pubmed: 23797954
J Neurol Neurosurg Psychiatry. 2015 Aug;86(8):873-8
pubmed: 25430934