scholarly journals Regulation of Schwann cell proliferation and apoptosis in PMP22-deficient mice and mouse models of Charcot-Marie-Tooth disease type 1A

Brain ◽  
2001 ◽  
Vol 124 (11) ◽  
pp. 2177-2187 ◽  
Author(s):  
S. Sancho
Keyword(s):  
Cell Proliferation ◽  
Schwann Cell ◽  
Mouse Models ◽  
Disease Type ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Proliferation And Apoptosis ◽  
Deficient Mice ◽  
Tooth Disease

scholarly journals Squalenoyl siRNA PMP22 nanoparticles are effective in treating mouse models of Charcot-Marie-Tooth disease type 1 A

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Suzan Boutary ◽  
Marie Caillaud ◽  
Mévidette El Madani ◽  
Jean-Michel Vallat ◽  
Julien Loisel-Duwattez ◽  
...  
Keyword(s):  
Mouse Models ◽  
Disease Type ◽  
Major Step ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Protein Levels ◽  
Positive Effects ◽  
Severity Of The Disease ◽  
Tooth Disease

AbstractCharcot-Marie-Tooth disease type 1 A (CMT1A) lacks an effective treatment. We provide a therapy for CMT1A, based on siRNA conjugated to squalene nanoparticles (siRNA PMP22-SQ NPs). Their administration resulted in normalization of Pmp22 protein levels, restored locomotor activity and electrophysiological parameters in two transgenic CMT1A mouse models with different severity of the disease. Pathological studies demonstrated the regeneration of myelinated axons and myelin compaction, one major step in restoring function of myelin sheaths. The normalization of sciatic nerve Krox20, Sox10 and neurofilament levels reflected the regeneration of both myelin and axons. Importantly, the positive effects of siRNA PMP22-SQ NPs lasted for three weeks, and their renewed administration resulted in full functional recovery. Beyond CMT1A, our findings can be considered as a potent therapeutic strategy for inherited peripheral neuropathies. They provide the proof of concept for a new precision medicine based on the normalization of disease gene expression by siRNA.

scholarly journals Nonmyelinating Schwann Cell Involvement With Well-Preserved Unmyelinated Axons in Charcot-Marie-Tooth Disease Type 1A

2007 ◽  
Vol 66 (11) ◽  
pp. 1027-1036 ◽  
Author(s):  
Haruki Koike ◽  
Masahiro Iijima ◽  
Keiko Mori ◽  
Masahiko Yamamoto ◽  
Naoki Hattori ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Disease Type ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Unmyelinated Axons ◽  
Tooth Disease

scholarly journals Allele-specific RNA interference prevents neuropathy in Charcot-Marie-Tooth disease type 2D mouse models

2019 ◽  
Vol 129 (12) ◽  
pp. 5568-5583 ◽  
Author(s):  
Kathryn H. Morelli ◽  
Laurie B. Griffin ◽  
Nettie K. Pyne ◽  
Lindsay M. Wallace ◽  
Allison M. Fowler ◽  
...  
Keyword(s):  
Rna Interference ◽  
Mouse Models ◽  
Disease Type ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Allele Specific ◽  
Tooth Disease

MicroRNAs as Biomarkers of Charcot-Marie-Tooth Disease Type 1A

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012266
Author(s):  
Hongge Wang ◽  
Matthew Davison ◽  
Kathryn Wang ◽  
Tai-he Xia ◽  
Katherine M. Call ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Schwann Cells ◽  
Motor Nerve ◽  
Disease Type ◽  
Class Iii ◽  
Protein Biomarkers ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Compound Muscle Action Potentials ◽  
Tooth Disease

Objective:To determine if microRNA’s (miR) are elevated in the plasma of individuals affected by the inherited peripheral neuropathy Charcot-Marie-Tooth Disease, type 1A (CMT1A), miR profiling was employed to compare control and CMT1A plasma.Methods:We performed a screen of CMT1A and control plasma samples to identify miRs that are elevated in CMT1A using next generation sequencing, followed by validation of selected miRs by quantitative PCR, and correlation with protein biomarkers and clinical data: Rash-modified CMT Examination and Neuropathy Scores (CMTES-R and CMTNS-R), ulnar compound muscle action potentials (CMAP), and motor nerve conduction velocities (MNCV).Results:After an initial pilot screen, a broader screen confirmed elevated levels of several muscle-associated miRNAs (miR1, -133a, -133b, and -206, known as myomiRs) along with a set of miRs that are highly expressed in Schwann cells of peripheral nerve. Comparison to other candidate biomarkers for CMT1A (e.g. Neurofilament L, NfL) measured on the same sample set shows a comparable elevation of several miRs (e.g. miR133a, -206, -223) and ability to discriminate cases from controls. NfL levels were most highly correlated with miR133a. In addition, the putative Schwann cell miRs (e.g. miR223, -199a, -328, -409, and -431) correlate with the recently described TMPRSS5 protein biomarker that is most highly expressed in Schwann cells and also elevated in CMT1A plasma.Conclusions:These studies identify a set of miRs that are candidate biomarkers for clinical trials in CMT1A. Some of the miRs may reflect Schwann cell processes that underlie the pathogenesis of the disease.Classification of Evidence:This study provides Class III evidence that a set of plasma miRs are elevated in patients with CMT1A.

scholarly journals Ndrg1-Deficient Mice Exhibit a Progressive Demyelinating Disorder of Peripheral Nerves

2004 ◽  
Vol 24 (9) ◽  
pp. 3949-3956 ◽  
Author(s):  
Tomohiko Okuda ◽  
Yujiro Higashi ◽  
Koichi Kokame ◽  
Chihiro Tanaka ◽  
Hisato Kondoh ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Schwann Cells ◽  
Peripheral Nerves ◽  
Sensory Neuropathy ◽  
Disease Type ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Hind Limbs ◽  
Deficient Mice ◽  
Tooth Disease

ABSTRACT NDRG1 is an intracellular protein that is induced under a number of stress and pathological conditions, and it is thought to be associated with cell growth and differentiation. Recently, human NDRG1 was identified as a gene responsible for hereditary motor and sensory neuropathy-Lom (classified as Charcot-Marie-Tooth disease type 4D), which is characterized by early-onset peripheral neuropathy, leading to severe disability in adulthood. In this study, we generated mice lacking Ndrg1 to analyze its function and elucidate the pathogenesis of Charcot-Marie-Tooth disease type 4D. Histological analysis showed that the sciatic nerve of Ndrg1-deficient mice degenerated with demyelination at about 5 weeks of age. However, myelination of Schwann cells in the sciatic nerve was normal for 2 weeks after birth. Ndrg1-deficient mice showed muscle weakness, especially in the hind limbs, but complicated motor skills were retained. In wild-type mice, NDRG1 was abundantly expressed in the cytoplasm of Schwann cells rather than the myelin sheath. These results indicate that NDRG1 deficiency leads to Schwann cell dysfunction, suggesting that NDRG1 is essential for maintenance of the myelin sheaths in peripheral nerves. These mice will be used for future analyses of the mechanisms of myelin maintenance.

scholarly journals MpzR98C arrests Schwann cell development in a mouse model of early-onset Charcot–Marie–Tooth disease type 1B

Brain ◽  
2012 ◽  
Vol 135 (7) ◽  
pp. 2032-2047 ◽  
Author(s):  
Mario A. C. Saporta ◽  
Brian R. Shy ◽  
Agnes Patzko ◽  
Yunhong Bai ◽  
Maria Pennuto ◽  
...  
Keyword(s):  
Schwann Cell ◽  
Mouse Model ◽  
Early Onset ◽  
Cell Development ◽  
Disease Type ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Schwann Cell Development ◽  
Tooth Disease
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