Lets hope there is some hope for  Huntington's - it is really ghastly.
Thanks to the French. Ray
----- Original Message -----
From: "M.Schild" <[log in to unmask]>
To: <[log in to unmask]>
Sent: Tuesday, February 21, 2006 8:12 AM
Subject: Anti-rejection Drug For The Treatment Of Huntington's Disease


Neurology/Neuroscience

 Article Date: 07 Feb 2006 - 4:00am (UK)

At the Institut Curie, CNRS and Inserm researchers have shown that
Huntington's disease may be treated using the drug FK506, which is also used
clinically to prevent graft rejection. Like Alzheimer's and Parkinson's,
Huntington's disease is characterized by the abnormal death of neurons.

 The Institut Curie researchers have discovered that FK506 blocks the
toxicity
of the protein huntingtin, which causes the death of certain neurons leading
to disease onset. FK506 is already used in a clinical setting and so is a
candidate for fast-track development as a treatment for Huntington's
disease.

 This study was published in the February 1, 2006 issue of The Journal of
Neuroscience.

 Huntington's disease is a genetic disorder which affects approximately 6
000
people in France and is of concern to over 12 000 carriers of the mutated
gene as yet untouched by clinical signs. It is characterized by uncontrolled
movements, personality changes, dementia and death 10 to 20 years after
onset
of the first symptoms (see "Additional information").

 Huntington's disease results from changes in the IT15 gene, which encodes a
protein, huntingtin, whose function is incompletely elucidated. Normal
huntingtin contains repeats of the amino acid glutamine, but mutant
huntingtin contains more than 35 to 40 glutamines and induces the disease.
Symptoms occur earlier as the number of repeats increases.

 This abnormal expansion of the polyglutamine tract in huntingtin results in
structural changes, and the mutant huntingtin accumulates in neurons thereby
causing their dysfunction and ultimately their death.

 The same type of mutation causes other neurodegenerative diseases, each
involving different regions of the brain. In Huntington's disease,
degeneration occurs in the neurons of the striatum, which are involved in
the
control of movement.

 Raúl Pardo and Emilie Colin at the Institut Curie are studying the
mechanisms
that lead to neuron death in Huntington's disease, under the direction of
Frédéric Saudou and Sandrine Humbert(1).

 They have now shown that calcineurin, a protein abundant in the brain,
chemically alters mutant huntingtin, which becomes more toxic for neurons.

 They have also discovered that by inhibiting calcineurin, FK506 "corrects"
this chemical alteration in mutant huntingtin both in cultured neurons and
in
an animal model of the disease. FK506 even prevents the death of the
striatal
neurons. So, FK506 negates the harmful effects of mutant huntingtin in
neurons.

 FK506 is already used therapeutically to prevent graft rejection, and so
may
be a candidate for fast-track development as a treatment for Huntington's
disease.

 When apoptosis goes awry...

 In all organisms, cells grow, reproduce and then die. But their death
occurs
in various ways. They may die accidentally - necrosis - or "decide" to die -
apoptosis, or programmed death. Apoptosis removes superfluous cells and rids
the body of potentially harmful damaged cells. The least anomaly in
apoptosis
may result in dysfunction, leading to a variety of diseases:

 -- when apoptosis is blocked, damaged cells are no longer eliminated and so
there is a risk of cancer.

 -- when programmed cell death is accelerated, there is abnormal loss of
neurons, leading to certain neurodegenerative disorders, such as
Alzheimer's,
Parkinson's, and Huntington's diseases.

 Huntington's Disease

 Huntington's disease, also known as Huntington's chorea, is a rare
neurological disorder affecting one person in 10,000 whose onset occurs
between the ages of 35 and 50. The most striking symptoms are involuntary
and
abnormal saccadic movements of the limbs, head and neck (chorea). There are
also mental disorders (anxiety, irritability, depression) and intellectual
deterioration progressing to dementia. Death due to complications (pulmonary
embolism, pneumonia, or other infection) occurs 15 to 20 years after disease
onset.

 Clinical diagnosis is often difficult and time-consuming because of the
highly variable symptoms that are easily confused with those of psychotic
disorders. Diagnosis must be confirmed by magnetic resonance imaging of the
brain and genetic testing. When there is a family history of the disease,
predictive genetic testing is possible but should be considered carefully
since the first symptoms appear relatively late in life and, at present,
there are no treatments to delay onset or slow progression of the disease.

 Huntington's disease is an autosomal dominant disorder: when one of the
parents carries the mutant gene, 50% of the offspring will inherit the
mutation and one day develop the disease. The IT15 gene which causes
Huntington's disease is on chromosome 4 and encodes the protein huntingtin.
Normal huntingtin contains repeats of an amino acid, glutamine, but mutant
huntingtin contains more than 35 to 40 glutamines and induces the disease.
Symptom onset occurs earlier when there are more repeats.

 The work of Frédéric Saudou's team (Inserm) is funded by the Institut
Curie,
the Ministry of Research, and the CNRS, and is supported by the Fondation
pour la Recherche Médicale (FRM), the Fondation BNP-Paribas, the Association
pour la Recherche sur le Cancer (ARC), the Association Française contre les
Myopathies, the Young Investigator Programme of the European Molecular
Biology Organization (EMBO) and Provital.

 (1) Inserm director of research Frédéric Saudou and Inserm senior research
associate Sandrine Humbert work in the "Intracellular signaling and cell
death" group of CNRS/Institut Curie Research Unit 146.

 http://www.jneurosci.org

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