This was reported on Hunt-Dis. The article's author errs in calling HD
"untreatable" vs its current common description of "incureable". As. Dr.
Goodman advises "remember the (albeit limited) treatments available now so that
we can more likely be there to benefit from the better ones coming."

Huntington's disease meets its match
17:42 06 June 2006
Peter Aldhous
NewScientist.com news service
http://www.newscientist.com/article/dn9287-huntingtons-disease-meets-its-match-.\
html

Huntington's disease may be about to meet its match with the development of a
therapy designed to knock out production of the defective protein that causes
the condition.

Huntington's is an untreatable inherited disease in which repetitive sequences
of DNA lead to the production of a faulty version of a protein called
huntingtin, giving it multiple copies of the amino acid glutamine. As adults,
its victims lose their cognitive abilities, suffer involuntary movements and,
after a decade or more, die. This week at the American Society of Gene Therapy
meeting in Baltimore, Maryland, researchers led by Beverly Davidson of the
University of Iowa described their progress treating the disease with a
technique called RNA interference, or RNAi. RNAi uses short sequences of RNA
just over 20 bases long to trigger a natural "gene-silencing" mechanism,
shutting down the production of specific proteins by targeting the RNA that
carries the instructions for making them.

Blocked message

Last year, Davidson raised the hopes of people carrying the Huntington's gene
when she used engineered viruses to treat mice with the mutated gene. The
viruses produce "small interfering" RNA sequences designed to block the RNA
carrying the message to make huntingtin. When injected into the mice's brains,
the viruses reduced levels of the protein and improved the animals' behavioural
symptoms. However, Huntington's patients have one mutated and one normal copy
of the huntingtin gene, and the small interfering RNA used in Davidson's initial
experiments targets abnormal and normal huntingtin alike. The protein is
important for embryological development, but its function in the adult brain is
unclear.

Davidson is now looking for methods to silence only the abnormal gene. For the
40 per cent of Huntington's patients who carry a particular version of the gene
she may have the answer. This version has a second mutation which her team has
been able to target exclusively with a small interfering RNA sequence.

Very optimistic

So far the experiments have only been carried out in cultured cells, and
Davidson, who is collaborating with Sirna Therapeutics, a firm based in San
Francisco, US, warns that it may be several years before the therapy is ready
for testing in people. "We need to be careful and do good science, but we're
very optimistic," she says.
Gene therapists are also optimistic that RNAi will prove effective against other
devastating neurodegenerative conditions, such as Alzheimer's disease.

Researchers led by Inder Verma of the Salk Institute for Biological Studies in
La Jolla, California, and Fred "Rusty" Gage of the University of California, San
Diego, have already used RNAi to target an enzyme called beta-secretase, which
is involved in the formation of the protein plaques that accumulate in the
brains of Alzheimer's patients. They have found that the treatment restores the
ability of mice with an Alzheimer's-like condition to perform in a water maze
test, in which they have to remember the position of a submerged platform. "It's
pretty impressive," says Verma, who hopes to begin experiments in monkeys by the
end of the year.


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