UCLA study identifies 2 chemicals that could lead to new drugs for genetic disor

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UCLA study identifies 2 chemicals that could lead to new drugs for genetic

disorders

http://www.eurekalert.org/pub_releases/2009-09/uoc--usi092509.php

Discovery could help people with cancer, muscular dystrophy, A-T

UCLA scientists have identified two chemicals that convince cells to ignore

premature signals to stop producing important proteins. Published in the Sept.

28 edition of the Journal of Experimental Medicine, the findings could lead to

new medications for genetic diseases, such as cancer and muscular dystrophy,

that are sparked by missing proteins.

" When DNA changes, such as nonsense mutations, occur in the middle rather than

the end of a protein-producing signal, they act like a stop sign that tells the

cell to prematurely interrupt protein synthesis, " explained Dr. Gatti,

professor of pathology and laboratory medicine and human genetics at the

Geffen School of Medicine at UCLA. " These nonsense mutations cause the loss of

vital proteins that can lead to deadly genetic disorders. "

Gatti's lab specializes in studying ataxia-telangiectasia (A-T), a progressive

neurological disease that strikes young children, often killing them by their

late teens or early 20s.

For four years, the UCLA Molecular Shared Screening Resources Center of the

campus' California NanoSystems Institute has screened 35,000 chemicals,

searching for those that ignore premature stop signals.

First author Liutao Du developed the screening technology in Gatti's laboratory.

" Of the dozens of active chemicals we discovered, only two were linked to the

appearance and function of ATM, the protein missing from the cells of children

with A-T, " said Du. " These two chemicals also induced the production of

dystrophin, a protein that is missing in the cells of mice with a nonsense

mutation in the muscular dystrophy gene. "

The UCLA team is optimistic that their discovery will aid pharmaceutical

companies in creating drugs that correct genetic disorders caused by nonsense

mutations. This could affect one in five patients with most genetic diseases,

including hundreds of thousands of people suffering from incurable diseases.

Because nonsense mutations can lead to cancer, such drugs may also find uses in

cancer treatment.

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Gatti's lab is funded by the Los Angeles-based Ataxia-Telangiectasia Medical

Research Foundation, the National Institutes of Health and the New York-based

Ataxia-Telangiectasia Ease Foundation.

The study's coauthors included Damoiseaux, Shareef Nahas, Kun Gao,

Hailiang Hu, nne Pollard, Jimena Goldstine, Jung, Henning and

Carmen Bertoni, all of UCLA.