Dataset
Data from: Schwann cell transcript biomarkers for hereditary neuropathy skin biopsies
Dryad
12/26/2024
DOI: 10.5061/dryad.hqbzkh1st
Abstract
Charcot-Marie-Tooth (CMT) disease is most commonly caused by duplication
of a chromosomal segment surrounding Peripheral Myelin Protein 22, or the
PMP22 gene, which is classified as CMT1A. Several candidate therapies
reduce Pmp22 mRNA levels in CMT1A rodent models, but the 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 the
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.
Details
- Title: Subtitle
- Data from: Schwann cell transcript biomarkers for hereditary neuropathy skin biopsies
- Creators
- John Svaren - University of Wisconsin–MadisonMichael Shy - University of Iowa
- Resource Type
- Dataset
- DOI
- 10.5061/dryad.hqbzkh1st
- Publisher
- Dryad
- Grant note
- U54NS065712 / National Institute of Neurological Disorders and Stroke (https://ror.org/01s5ya894)
- Language
- English
- Date published
- 12/26/2024
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9985027359502771
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