closing in on treatment for CMT with HSPs

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From EurekAlert May 7, 2004

Closing in on treatment for Charcot-Marie-Tooth disease?

Ann Van Gysel

VIB, Flanders Interuniversity Institute of Biotechnology

Charcot-Marie-Tooth (CMT) is a hereditary disorder of the peripheral

nervous system that strikes 1 person in every 2500. Increasing

debilitation of the muscles ultimately leads to their disappearance in

the lower legs, feet and hands. Now, researchers from VIB (the Flanders

Interuniversity Institute for Biotechnology) have discovered a piece of

the molecular puzzle of this disease. Two small 'heat shock' proteins

turn out to be crucial - faults in the coding genes lead to the disease.

Additional research has shown that these proteins play an important role

in many other neurodegenerative disorders as well. This research moves

us a step closer to the development of new therapies.

CMT, a serious disorder without a cure.

CMT, the most common hereditary disorder of the peripheral nervous

system, leads to debilitation of the muscles in the lower legs, feet and

hands. The clinical picture is extremely variable, but older patients

sometimes require a wheelchair. Today, only supportive treatment is

available; there are still no effective therapies to retard or stop the

progress of the disease. More insight into the molecular processes of

this disease is essential for diagnosis and potential treatment. And

exploration of the genes involved is a crucial step in this.

VIB research findings

Joy Irobi and her colleagues - under the direction of Timmerman

and De Jonghe of the Department of Molecular Genetics, University

of Antwerp - are concentrating on the genetic and biological study of

hereditary disorders of the peripheral nervous system. The largest cells

in our body, our peripheral neurons can be 1 meter long in bundles of

nerve fibers extending from the spinal cord to the feet.

Recently, the researchers in Antwerp have found mutations in the genetic

code of two small 'heat shock' proteins (HSPs) in a number of people

with CMT. In stress situations, cells produce HSPs that act as

'chaperones', stabilizing other proteins and protecting against

degradation. The specific function of the two HSPs in our peripheral

nerves has not yet become clear, but the mutations that have been

discovered in several European families are now leading to serious

symptoms.

Toward new therapies

The scientists have shown that the mutations lead to a stronger

interaction between the two HSPs. This causes a precipitation in

cultured cells and reduces the viability of neurons. These findings

demonstrate the importance of HSPs in neurodegenerative disorders. The

team's research results will open the way for new progress in the

development of therapies for these hereditary nervous disorders. These

HSPs have previously been studied in Amyotrophic Lateral Sclerosis (ALS,

or Lou Gehrig's disease), a serious acquired disorder of the nervous

system. Hopefully, the discovery of the mutations in the two HSPs will

now lead to new insights into this disorder as well.