Posted on 12/01/2006 6:18:22 PM PST by annie laurie
At the Institut Curie, CNRS and Inserm researchers have shown that cysteamine, which is already used to treat a rare disease called cystinosis, prevents the death of neurons in Huntington’s disease. Like Alzheimer’s and Parkinson’s, Huntington’s disease, is characterized by the abnormal death of neurons.
Cysteamine raises neuronal levels of BDNF protein, a trophic factor which is depleted in Huntington’s disease, and by assaying BDNF in the blood it is possible to evaluate the effect of treatment. If other studies confirm these results, cysteamine could soon be used to treat Huntington’s disease, and BDNF could serve as a biomarker of its efficacy.
Huntington’s disease is a rare (1 in 10 000 people) neurological condition whose onset occurs between the ages of 35 and 50. The most striking symptoms are involuntary abnormal movements of the limbs, head and neck. These are accompanied by mental symptoms (anxiety, irritability, depression) and intellectual deterioration leading to dementia. Death occurs 15 to 20 years after disease onset as a result of complications (pulmonary embolism, pneumonia, other infection). Clinical diagnosis is often difficult and time-consuming because the symptoms are highly variable and easy to confuse with psychological disorders. It must be confirmed by examination of the brain (by magnetic resonance imaging) or by genetic testing.
A mutant protein: huntingtin
Huntington’s disease is an autosomal dominant inherited disorder: if one of the two parents carries the mutant gene, 50% of the offspring will inherit this mutation and one day develop the disease. The IT15 gene responsible for the disease is located on chromosome 4 and encodes a protein called huntingtin, whose function is unknown. Normal huntingtin contains repeats of glutamine, an amino acid, but when there are more than 35 to 40 glutamines, huntingtin is considered to be mutant and induces the death of neurons, thereby causing the disease. Symptoms appear increasingly early as the number of glutamine repeats increases.
The same type of mutation causes other neurodegenerative diseases, each of which specifically affects different regions of the brain. In Huntington’s disease, there is progressive loss of neurons of the striatum, a region of the brain involved in the control of movement.
Thwarting apoptosis of neurons
At the Institut Curie, Frédéric Saudou and Sandrine Humbert(1) have already shown that brain-derived neurotrophic factor (BDNF)(2), when present in adequate amounts in the striatal neurons, blocks the effect of mutant huntingtin(3). Conversely, when BDNF levels decrease, the disease progresses. In patients with Huntington’s disease, BDNF levels in the striatal neurons are subnormal.
Under the direction of Frédéric Saudou and Sandrine Humbert, Maria Borell-Pagès has now shown in a mouse model of Huntington’s disease that cysteamine raises BDNF levels in striatal neurons. Cysteamine stimulates the secretion of BDNF, which explains its neuroprotective effect in different murine models of the disease. Cysteamine is already used clinically to treat a rare childhood disease called cystinosis(4).
The present study also demonstrates that BDNF, which can be assayed in blood, can be used as a biomarker. BDNF levels are decreased in animal models of Huntington’s disease, and are raised by cysteamine. Assay of BDNF in the blood should therefore enable evaluation of the efficacy of cysteamine treatment. A national, multicenter clinical trial is scheduled to begin by the end of 2006, and will test the effect of cysteamine and the value of BDNF as a biomarker in about 100 patients.
If these conclusions are confirmed clinically, cysteamine could become a routine treatment for Huntington’s disease.
Ping
Just damn.
That about sums it up :(
An additional horror of this disease is that it's a dominant gene - you have a 50-50 chance of inheriting it from a parent with Huntington's. By the time it was diagnosed, the victim had almost always already married and had kids, passing it on to another generation.
It looks like Arlo Guthrie (of "Alice's Restaurant" fame) has dodged the bullet, I don't think he or any of his surviving siblings ever got tested, but he's well beyond the age when the first symptoms develop.
In the majority of cases, that's true. I personally know someone who had no symptoms until age 58. I hope Arlo will continue to 'dodge the bullet' ... it's a disease I certainly wouldn't wish on him, or on anyone else.
If I had already had kids, I might not, but if I hadn't yet, I think I would.
I wonder if modern medicine can to some extent mask the early symptoms . . . that might delay a diagnosis, except in retrospect.
I wouldn't wish this horrible disease on my very worst enemy.
Indeed.
I wonder if modern medicine can to some extent mask the early symptoms . . . that might delay a diagnosis, except in retrospect.
There are some medications in use currently, but they're not particularly effective (at least not in the case I know).
I wouldn't wish this horrible disease on my very worst enemy.
Ditto. Here's hoping that this research will speed the way toward a cure, or at least a treatment which can slow the progress of the disease.
You think nothing could possibly be more dreadful than a deadly genetic disease in an infant or child . . . then you think of this.
I am sorry for your friend, and I will pray for him.
Thank you so much for your kind words, and most especially for your prayers :)
You do?
Well, my niece has it. Her onset was probably at about age 47 or 48 but it didn't become totally apparent until a couple of years ago.
Her older brother has no symptoms but he is 58 and I was sure he was okay.
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.