Charcot Marie Tooth Syndrome

Mice point to a therapy for Charcot-Marie-Tooth disease

VIB researchers have developed a mouse model for Charcot-Marie-Tooth (CMT) neuropathy, a hereditary disease of the peripheral nervous system. They also found a potential therapy for this incurable disease. The treatment not only halted the damage to the nerves and the atrophy of the muscles, it even succeeded in reversing the symptoms. The research was conducted under supervision of Wim Robberecht en Ludo Van Den Bosch from VIB-K.U.Leuven, in collaboration with the team of Vincent Timmerman at VIB-University of Antwerp. The study was published in Nature Medicine .

CMT: a collection of neuropathies

Charcot-Marie-Tooth (CMT) disease is the name for a collection of hereditary disorders and affects approximately one in 2,500 individuals, making it the most common inherited disorder of the peripheral nervous system. CMT is characterized by loss of muscle tissue due to denervation and by sensory abnormalities, both predominantly in feet and legs but also in the hands and arms in advanced stages of the disease. Persons with CMT can be affected moderately to quite severely. It is presently not possible to cure or prevent CMT, which affects both children and adults. Research into the molecular biological process leading to CMT is important, because it contributes to the development of good diagnosis and offers possible treatments.

Earlier work by VIB researchers showed that some CMT patients have mutations in HSPB1, a gene coding for the 27 kDa small heat shock protein B1, a protein that plays a role in many stress-related molecular processes in the body. Until now, it was unclear how mutations in HSPB1 could lead to degeneration of the nerve bundles and to muscular weakness.

Mouse model for CMT

The core of the study by Constantin van Outryve d'Ydewalle consists of the construction of a mouse model for CMT. The researchers expressed the mutated human HSPB1 gene in mouse 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.

Eponymous Blog On Eponymous Diseases | DrPullen.com – Medical and ...

Eponymous means when something is named after a person.  In the office nearly every day I make a diagnosis of an eponymous illness, injury or disorder of some sort.  Some are so common that the eponym is much more recognizable than the medical name.  Probably more people know about Lou Gehrig’s disease than know about amytrophic lateral sclerosis.  Almost certainly more people know about Huntington’s Chorea than have heard of autosomal dominant chorea.  Do you think of Alzheimer ’s disease or primary senile degenerative dementia.   Do you think of your favorite major league pitcher needing an ulnar collateral ligament repair or needing Tommy John surgery?   Most of us know about Reye’s syndrome, Osgood- Schlatter Disease, and Marfan Syndrome.

Here are a few of my favorites with a brief description and why I like eponymous designation:

Bell’s Palsy:   Dr. Charles Bell was the Scottish anatomist who first described the facial nerve palsy that is usually caused by inflammation leading to dysfunction of the facial nerve on one side of the face and leading to drooping of that side of the face.

Charcot-Marie-Tooth Disease:   This is often so commonly used as to be referred to by its acronym CMT disease.  This hereditary disorder has become very well understood in recent years and the exact genetic mutations are able to be used to make specific diagnoses.  These details were of course unknown to Dr. Jean-Marie Charcot, Pierre Marie and  Howard Henry Tooth for whom the disorder was named when they described it in 1886.

Down’s Syndrome:   Named after Dr. John Langdon Down, Down’s Syndrome is so much kinder and compassionate than the older Mongoloid terminology that Dr. Down used in 1866 when he described the condition.

Grave’s Disease:   Named for Robert James Graves, this is the most common cause of hyperthyroidism, and is sometimes associated with bulging eyes called exopthalmos and deposition of material in the subcutaneous area of the legs causing what is called pretibial myxedema.

Hirschsprung Disease:   named for Harold Hirschsprung, a Danish physician who described the condition.   I’m happy not to have to call it congenital aganglionic megacolon which is far too much of a tongue twister.

Osler-Weber-Rendu syndrome:  You have to love anything named after Sir William Osler.  It must be pretty cool for Henri Jules Louis Marie Rendu and Frederick Parkes Weber to have their names also associated with the same eponymous disease. This is also known as HHT for hereditary hemorrhagic telangectasia.  It is reasonably common, occurring in about 1:5000 people in most areas of the world.  It is an autosomal dominant condition with genetic testing available for diagnosis when it is suspected.

The Charcot-Marie-Tooth Syndrome, a population genetic study in South Wales

Hereditary peripheral neuropathies

Neuromuscular function and disease, basic, clinical, and electrodiagnostic aspects

A-Z of syndromes and inherited disorders, a manual for health, social, and education workers

Principles of molecular medicine