Conduction block in PMP22 deficiency - HNPP

[Guest guest]

Conduction block in PMP22 deficiency.

J Neurosci. 2010 Jan 13;30(2):600-8

Bai Y, Zhang X, Katona I, Saporta MA, Shy ME, O'Malley HA, Isom LL, Suter U, Li

J.

Department of Neurology, Wayne State University, Detroit, Michigan, USA.

Patients with PMP22 deficiency present with focal sensory and motor deficits

when peripheral nerves are stressed by mechanical force. It has been

hypothesized that these focal deficits are due to mechanically induced

conduction block (CB).

To test this hypothesis, we induced 60-70% CB (defined by electrophysiological

criteria) by nerve compression in an authentic mouse model of hereditary

neuropathy with liability to pressure palsies (HNPP) with an inactivation of one

of the two pmp22 alleles (pmp22(+/-)).

Induction time for the CB was significantly shorter in pmp22(+/-) mice than that

in pmp22(+/+) mice. This shortened induction was also found in myelin-associated

glycoprotein knock-out mice, but not in the mice with deficiency of myelin

protein zero, a major structural protein of compact myelin. Pmp22(+/-) nerves

showed intact tomacula with no segmental demyelination in both noncompressed and

compressed conditions, normal molecular architecture, and normal concentration

of voltage-gated sodium channels by [(3)H]-saxitoxin binding assay.

However, focal constrictions were observed in the axonal segments enclosed by

tomacula, a pathological hallmark of HNPP. The constricted axons increase axial

resistance to action potential propagation, which may hasten the induction of CB

in Pmp22 deficiency. Together, these results demonstrate that a function of

Pmp22 is to protect the nerve from mechanical injury.

[Guest guest]

Hello Gretchen and All,

Seeing that I'm one of the HNPP people, I was particularly interested in the

experiment and the results. Although I had to read it three times, I think the

gist is mice with induced tomaculi exhibit axonal transmission deficiency due to

mechanical compression. Therefore, a function of PMP-22 is to protect the axons

from mechanical damage. In any case, it is still understood that lack of or

reduced enervation causes selective muscle deterioration thereby unbalancing

many muscle opposing twins that provide us with ranges of motion and control.

When we are young and growing rapidly, the results are usually minimal

and at some age we begin to have serious muscle deficiencies that produce a host

of problems in body locomotion. It is important to understand that this is with

us from the moment of conception and not something we " catch " later on.

With that in mind, I favor an early genetic test and carefully controlled

upbringing to optimize meeting the physical problems no matter how slight or

serious they may turn out to be. I think that I was very lucky in that my

activities and schooling just happened to be that well considered even though it

took 59 years to determine what the problem was.

Short of a zygote intervention, I think what we need is a very well

considered primer for parents and officials with sway over young people so that

their lives and development can be optimized no matter what thedisease may

produce for the individual !

I hope that some day a person with a broad enough view of the disease can bring

it all together and do this for those yet to come. We already know that this is

not an " orphan " disease and that a very significant segment of the world's

population is short changed in life because of it.

I'm for everybody dealing with this disease knowing as much as they can absorb

and we who have it should undertake that education above all others. Think of

cancer or heart disease, CMT/HNPP should be so focused as well.

EdM from NH