Clue to treatments for fatal Huntington's

New Scientist ^ | June 30,2002 | Robin Orwant

[gcruse]

 
 
            Clue to treatments for fatal Huntington's
 
            19:00 30 June 02
            Robin Orwant
 
            The genetic defect behind Huntington's disease causes malfunctions in mitochondria, the
            energy-producing components of cells, new work shows. The finding should help explain how the
            mutation causes the disease and could lead to new approaches to treatment.

            Since 1993, researchers have known that Huntington's - an incurable and fatal brain disorder - is caused
            by a defect in a single gene that encodes a protein called huntingtin.

            They have also long suspected that some of the symptoms of the disorder are due to defects in
            mitochondria. Now, for the first time, a team led by Alexander Panov at Emory University, US, have
            directly linked the two.

            Panov's work suggests that hungtintin kills brain cells, at least in part, by causing mitochondria in the
            cells to respond abnormally to a type of chemical stress. This causes the mitochondria to spill some of
            their contents. And this could cause cell death, Panov thinks.

            "This study brings together several lines of research," says Elena Cattaneo, a pharmacologist at the
            University of Milan. "It shows how the mitochondria are linked to the toxicity of the mutant gene."
 

            New drugs

            Panov's team examined mitochondria from blood cells of patients with Huntington's disease and from
            brain cells of engineered mice that produce mutant huntingtin. They found that these mitochondria could
            not handle a certain kind of stress caused by calcium as well as normal mitochondria.

            The researchers also found that mutant huntingtin can bind directly to normal mitochondria and cause
            them to respond abnormally to calcium-induced stress. This "stress" happens during part of the normal
            signalling process in the brain.

            Cattaneo believes the finding could lead to new drugs that would alleviate some of the symptoms of the
            disorder by correcting the defective mitochondria. "This may really open up some new perspectives for
            treating Huntington's disease," she says.

            But M. Flint Beal, a neuroscientist at Cornell University, believes that more experiments must be done
            to determine whether the mitochondrial defect that Panov has observed really causes Huntington's
            disease.
 

            Other factors

            "I'm not entirely sure that this is the whole story in the living person," he argues. "They haven't proven
            that this [mitochondrial defect] causes what happens in patients."

            Panov agrees that mutant huntingtin might cause cell death and disease by affecting other factors
            besides the mitochondria.

            "What I've discovered is one mechanism," he admits. "But it's probably not the only one."

            Huntington's disease affects one in 10,000 people. A child of a sufferer has a 50 per cent chance of
            developing the disease. Journal reference: Nature Neuroscience (DOI: 10.1038/nn884)
 
            19:00 30 June 02