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Mice point to a therapy for Charcot-Marie-Tooth disease
Date:8/2/2011

use neurons. The mouse model develops motor symptoms, muscle atrophy and weakness, foot deformities and steppage gait, all very similar to symptoms observed in affected individuals. Furthermore, the mice develop sensory problems that also occur in CMT patients. Pathological examination of the nerves of the CMT mice shows that the contact between the nerve endings and muscles is disturbed.

Axonal transport deficits

The CMT mice provide the unique possibility to isolate and culture affected nerve cells, making it possible to investigate what exactly goes wrong in the sick nerves. It was discovered that the transport of mitochondria (the cellular power plants) within the axons is severely disturbed in the neurons from symptomatic CMT mice, most likely because the tracks along which the mitochondria are transported (microtubules) are damaged. This could lead to a chronic lack of sufficient mitochondria and other transported cargoes at the nerve endings, causing the nerves to degenerate.

Possible treatment of CMT by HDAC6 inhibitors

These new insights also open possibilities for treatment, because the mitochondrial transport in nerve fibers is known to be affected by tubulin deacetylation, a posttranslational modification of the building blocks of microtubules catalyzed by histone deacetylase 6 (HDAC6). Inhibitors of HDAC6 do not only reverse the axonal transport deficits in vitro, treatment of the CMT mice with HDAC6 inhibitors also halts the damage to the nerves and even succeeds in reversing the symptoms, most likely by muscle reinnervation. The most specific therapeutic molecule used in this study (Tubastatin A) was made by Alan Kozikowski from the University of Illinois at Chicago (USA).

Mouse medicine is not the same as human medicine

There is still a long way to go before these drugs will become available for patients. Many experimental drugs even those that are successful in animal models fail dur
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Contact: Joris Gansemans
joris.gansemans@vib.be
32-477-697-668
VIB (the Flanders Institute for Biotechnology)
Source:Eurekalert

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