CMT 2E: Reversal of neuropathy phenotypes in conditional mouse model

[Guest guest]

Hum Mol Genet. 2010 Apr 26

Reversal of neuropathy phenotypes in conditional mouse model of

Charcot-Marie-Tooth disease type 2E.

Dequen F, Filali M, Lariviére RC, Perrot R, Hisanaga SI, n JP.

Research Centre of CHUQ and Department of Psychiatry and Neurosciences, Laval

University, Québec, Canada.

Abstract

Mutations in the gene encoding for the neurofilament light subunit (NF-L) are

responsible for Charcot-Marie-Tooth (CMT) neuropathy type 2E.

To address whether CMT2E disease is potentially reversible, we generated a mouse

model with conditional doxycycline-responsive gene system that allows repression

of mutant hNF-L(P22S) transgene expression in adult neurons.

The hNF-L(P22S);tTa transgenic mice recapitulated key features of CMT2E disease

including aberrant hindlimb posture, motor deficits, hypertrophy of muscle

fibers and loss of muscle innervation without neuronal loss.

Remarkably, a three-month treatment of hNF-L(P22S);tTa mice with doxycycline (an

antibiotic!) after onset of disease efficiently down-regulated expression of

hNF-L(P22S) and it caused reversal of CMT neurological phenotypes with

restoration of muscle innervation and of neurofilament protein distribution

along the sciatic nerve.

These data suggest that therapeutic approaches aimed at abolishing expression or

neutralizing hNF-L mutants might not only halt the progress of CMT2E disease,

but also revert the disabilities.

[Guest guest]

Hasn't there also been other research, or personal stories, of antibiotic use

and an improvement in one's CMT?

We all probably just have some type of as yet undiscovered bacterial, or viral,

infection.

>

> Hum Mol Genet. 2010 Apr 26

>

> Reversal of neuropathy phenotypes in conditional mouse model of

Charcot-Marie-Tooth disease type 2E.

>

> Dequen F, Filali M, Lariviére RC, Perrot R, Hisanaga SI, n JP.

>

> Research Centre of CHUQ and Department of Psychiatry and Neurosciences, Laval

University, Québec, Canada.

>

> Abstract

> Mutations in the gene encoding for the neurofilament light subunit (NF-L) are

responsible for Charcot-Marie-Tooth (CMT) neuropathy type 2E.

>

> To address whether CMT2E disease is potentially reversible, we generated a

mouse model with conditional doxycycline-responsive gene system that allows

repression of mutant hNF-L(P22S) transgene expression in adult neurons.

>

> The hNF-L(P22S);tTa transgenic mice recapitulated key features of CMT2E

disease including aberrant hindlimb posture, motor deficits, hypertrophy of

muscle fibers and loss of muscle innervation without neuronal loss.

>

> Remarkably, a three-month treatment of hNF-L(P22S);tTa mice with doxycycline

(an antibiotic!) after onset of disease efficiently down-regulated expression of

hNF-L(P22S) and it caused reversal of CMT neurological phenotypes with

restoration of muscle innervation and of neurofilament protein distribution

along the sciatic nerve.

>

> These data suggest that therapeutic approaches aimed at abolishing expression

or neutralizing hNF-L mutants might not only halt the progress of CMT2E disease,

but also revert the disabilities.

>

[Guest guest]

I have not found any published research on antibiotic use improving * any type*

of CMT. You can search pub med and come up with zero. As for personal stories,

well I have had major antibiotic therapy at several times in my life. However, I

do not know if I have Type 2E or not. But I * do know * I have some form of CMT

Type 2. My symptoms are very mild, but before I had the antibiotic therapy (for

reasons unrelated to CMT), I had pretty bad symptoms: rotten balance, major

muscle spacisty, major fatigue, etc.

I don't have those symptoms now. But then I've also had alot of PT, have

exercised consistently, and have learned to listen to my body and respond to *

potential * fatigue wisely. It is quite possible that one of the 15 compounds

tested so far in HTS is an antibiotic of some sort. Also take into account this

research was done out of the USA.

There is still much we don't know about CMT.

Gretchen