Featured Research

from universities, journals, and other organizations

UCLA Scientists Discover New Way To Fix Defective A-T Gene; Findings May Apply To Cancer, Other Genetic Diseases

Date:
October 19, 2004
Source:
University Of California Los Angeles
Summary:
UCLA scientists have devised a novel way to repair one of the genetic mutations that causes ataxia-telangiectasia, (A-T), a life-shortening disorder that devastates the neurological and immune systems of one in 40,000 young children. Reported Oct. 18 in the Proceedings of the National Academy of Sciences, the findings could hold far-reaching implications for treating A-T, cancer and other genetic diseases.

UCLA scientists have devised a novel way to repair one of the genetic mutations that causes ataxia-telangiectasia, (A-T), a life-shortening disorder that devastates the neurological and immune systems of one in 40,000 young children. Reported Oct. 18 in the Proceedings of the National Academy of Sciences, the findings could hold far-reaching implications for treating A-T, cancer and other genetic diseases.

Related Articles


Often misdiagnosed as cerebral palsy, A-T usually strikes children before age 2 and confines them to a wheelchair by age 10. Many lose their ability to speak, and die in childhood. One in three of these children also develop lymphoma or leukemia. Adults who carry the mutated A-T gene (ATM), including up to 15 percent of breast-cancer patients, are eight times more likely to develop cancer than the general population.

Dr. Richard Gatti, professor of pathology and laboratory medicine, and Chih-Hung Lai, a postdoctoral researcher at the David Geffen School of Medicine at UCLA, created a new strategy for tricking the ATM gene into overlooking certain types of mutations called premature termination codons (PTCs).

"PTCs are like irregular stop signs located in the middle of the block," Gatti said. "They stop traffic before it reaches the intersection. We made these stop signs invisible, so traffic continues until it sees the proper stop sign at the end of the corner."

In normal cells, termination codons alert the cell's protein-reading machinery that a protein has reached full length and completed copying. In the mutated genes of A-T patients, PTCs halt the copying of proteins too early, resulting in shortened and unstable ATM proteins.

"Unstable proteins create abnormal cells that can't function properly, producing all of the neurological and immune problems that afflict A-T patients," said Lai, the study's first author.

Lai and Gatti noted that A-T patients whose cells contain no ATM protein suffer from a severe form of the disease, while patients whose cells hold some ATM protein have a milder form of the disorder. The scientists hypothesized that increasing ATM protein in the cells, even by modest amounts, might alleviate A-T patients' symptoms or perhaps eliminate the disease entirely.

The team used a group of antibiotics called aminoglycosides to make the PTCs invisible to the cell's protein-reading machinery. After bathing in the antibiotics for four days, cells that earlier contained little or no ATM proteins had grown full-length ATM proteins.

When the researchers tested the treated A-T cells, they also discovered that the cells had converted to normal appearance and begun to function normally. The cells started churning out ATM protein, which provides energy by switching on other cells.

"About one in six A-T patients has a PTC type of mutation," Lai said. "We hope that our findings will provide a solid first step to gene-based therapy for this group."

According to Gatti, many aminoglycosides are already approved for clinical use by the FDA and could quickly become available for testing in A-T clinical trials.

"Our next step will be to build an ATM animal model and see how it responds to aminoglycoside therapy," Gatti said. "We will also screen other antibiotics and drugs that may restore ATM cell function even better. We only need one successful candidate to make a huge difference in the lives of children with A-T."

Because the ATM gene also increases cancer risk, Gatti is hopeful that his laboratory findings may hold implications for cancer diagnosis and treatment.

"If we are able to restore A-T cell function, we may be able to halt the spread of the tumor," Gatti said. "By correcting the mutation, the cancer may stop growing or recede entirely."

Everyone carries two copies of the A-T gene, but one copy is defective in A-T carriers. Children who inherit a defective gene from each parent will develop the disease. Gatti's laboratory was the first to locate the ATM on chromosome 11 and then worked to clone it successfully.

The National Institute for Neurological Disorders and Stroke and the A-T Medical Research Foundation funded the study.


Story Source:

The above story is based on materials provided by University Of California Los Angeles. Note: Materials may be edited for content and length.


Cite This Page:

University Of California Los Angeles. "UCLA Scientists Discover New Way To Fix Defective A-T Gene; Findings May Apply To Cancer, Other Genetic Diseases." ScienceDaily. ScienceDaily, 19 October 2004. <www.sciencedaily.com/releases/2004/10/041019092318.htm>.
University Of California Los Angeles. (2004, October 19). UCLA Scientists Discover New Way To Fix Defective A-T Gene; Findings May Apply To Cancer, Other Genetic Diseases. ScienceDaily. Retrieved March 3, 2015 from www.sciencedaily.com/releases/2004/10/041019092318.htm
University Of California Los Angeles. "UCLA Scientists Discover New Way To Fix Defective A-T Gene; Findings May Apply To Cancer, Other Genetic Diseases." ScienceDaily. www.sciencedaily.com/releases/2004/10/041019092318.htm (accessed March 3, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Tuesday, March 3, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Treadmill Test Can Predict Chance Of Death Within A Decade

Treadmill Test Can Predict Chance Of Death Within A Decade

Newsy (Mar. 2, 2015) Johns Hopkins researchers analyzed 58,000 heart stress tests to come up with a formula that predicts a person&apos;s chances of dying in the next decade. Video provided by Newsy
Powered by NewsLook.com
Going Gluten-Free Could Get You A Tax Break

Going Gluten-Free Could Get You A Tax Break

Newsy (Mar. 2, 2015) If a doctor advises you to remove gluten from your diet, you could get a tax deduction on the amount you spend on gluten-free foods. Video provided by Newsy
Powered by NewsLook.com
GlaxoSmithKline and Novartis Try Swapping Success

GlaxoSmithKline and Novartis Try Swapping Success

Reuters - Business Video Online (Mar. 2, 2015) GlaxoSmithKline and Novartis have completed a series of asset swaps worth more than $20 billion. As Grace Pascoe reports they say the deal will reshape both drugmakers. Video provided by Reuters
Powered by NewsLook.com
How Can West Africa Rebuild After Ebola?

How Can West Africa Rebuild After Ebola?

Reuters - Business Video Online (Mar. 2, 2015) How best to rebuild the three West African countries struggling with Ebola will be discussed in Brussels this week. As Hayley Platt reports Sierra Leone has the toughest job ahead - its once thriving economy has been ravaged by the disease. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins