Featured Research

from universities, journals, and other organizations

NCI Study Demonstrates That Cellular Defects In Premature Aging Disease Are Reversible

Date:
March 7, 2005
Source:
NIH/National Cancer Institute
Summary:
Cells affected by Hutchinson-Gilford Progeria Syndrome (HGPS) -— a disease associated with premature aging -- can be made healthy again, according to findings by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH).

Cells affected by Hutchinson-Gilford Progeria Syndrome (HGPS) -— a disease associated with premature aging -- can be made healthy again, according to findings by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). Using specially modified segments of DNA, NCI researchers Paola Scaffidi, PhD, and Tom Misteli, PhD, reversed the abnormalities seen in HGPS cells by correcting defects associated with the key protein, lamin A. By demonstrating that HGPS cellular characteristics are reversible, this study, appearing in Nature Medicine online on March 6, 2005*, brings scientists one step closer to understanding this devastating childhood disease and might provide insights into the normal aging process.

HGPS is a rare inherited disease affecting about one in eight million children. While appearing normal at birth, infants with HGPS age rapidly after their first 18 months, and physical symptoms include stunted growth, loss of hair and body fat, joint stiffness, osteoporosis, and heart problems. The condition is fatal, with heart disease being the leading killer, and affected children usually die before they reach their late teens.

Less than two years ago, NIH-led researchers discovered that the genetic basis for HGPS is a single mutation in the gene encoding lamin A. Lamin A is a critical structural protein that acts as the scaffolding which holds a cell’s nucleus together. Lamin A is defective in HGPS cells because the mutation creates an aberrant splice site in the lamin A gene; the aberrant splicing, or joining the separate parts of the gene together, results in synthesis of a truncated lamin protein. Without lamin A holding them together, the nuclei of progeria cells become wrinkled and misshapen. In addition, numerous other nuclear proteins show reduced expression.

“Our NCI team at the Center for Cancer Research in Bethesda set out to ask whether these cellular changes associated with progeria are permanent or reversible,” said Scaffidi. First, the investigators added DNA encoding normal lamin A into cells taken from patients affected with progeria, but observed that increased synthesis of normal lamin A did not correct any of the progeria-associated defects. In addition, they found that introduction of the mutant protein into healthy human cells was sufficient to produce the disease characteristics. “These results made it clear that in order to achieve a potential therapeutic effect, we needed to completely eliminate the mutant protein,” said Scaffidi.

The NCI researchers designed a chemically stable DNA oligonucleotide — a short DNA sequence that the cell wouldn’t be able to degrade — that would bind to the mutant splice site and prevent the splicing machinery from cutting in the wrong place. “You can think of it as a molecular Band-Aid®,” said Misteli. The researchers inserted their oligonucleotides into the progeria cells and observed that after four days almost all the mutant lamin A transcripts had been eliminated and replaced with the properly spliced counterpart. The oligonucleotide was highly specific to the mutated region and did not cover-up other splicing locations. One week after correcting the splicing defect, the mutant lamin A protein had been eliminated and more than 90 percent of progeria cells were restored to normal; visually, the nuclei lost their wrinkles and lobes and returned to a natural ellipsoid shape, and the expression of other nuclear proteins was also restored to normal levels.

“It’s amazing that we could take a cell that looked about ready to die, and a few days later it was healthy and ready to divide again,” said Misteli.

Misteli noted that these results demonstrate a proof-of-principle that the cellular effects of progeria can be reversed, meaning his laboratory’s method could be used some day in the future as a therapeutic strategy. The fact that a progeria reversal can be achieved in multiple cell types, and that the cells can return to normal, independent of cell division, bolsters this possibility. “Some tissues in our body do not divide,” Misteli pointed out. “So demonstrating that we can rescue the normal phenotype without cell division means this procedure could be effective in all tissues.” Misteli and his group will also look more closely at healthy cells to determine how similar progeria is to the normal aging process.

For more information about progeria, please visit the NHGRI Web site at http://www.genome.gov/11007255.

For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

###

* Paola Scaffidi and Tom Misteli, “Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford Progeria Syndrome.” Nature Medicine, vol 11, no 4; April 2005.


Story Source:

The above story is based on materials provided by NIH/National Cancer Institute. Note: Materials may be edited for content and length.


Cite This Page:

NIH/National Cancer Institute. "NCI Study Demonstrates That Cellular Defects In Premature Aging Disease Are Reversible." ScienceDaily. ScienceDaily, 7 March 2005. <www.sciencedaily.com/releases/2005/03/050307100013.htm>.
NIH/National Cancer Institute. (2005, March 7). NCI Study Demonstrates That Cellular Defects In Premature Aging Disease Are Reversible. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2005/03/050307100013.htm
NIH/National Cancer Institute. "NCI Study Demonstrates That Cellular Defects In Premature Aging Disease Are Reversible." ScienceDaily. www.sciencedaily.com/releases/2005/03/050307100013.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) — New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com
$23.6 Billion Awarded To Widow In Smoking Lawsuit

$23.6 Billion Awarded To Widow In Smoking Lawsuit

Newsy (July 20, 2014) — Cynthia Robinson claims R.J. Reynolds Tobacco Company hid the health and addiction risks of its products, leading to the death of her husband in 1996. Video provided by Newsy
Powered by NewsLook.com
Tooth Plaque Provides Insight Into Diets Of Ancient People

Tooth Plaque Provides Insight Into Diets Of Ancient People

Newsy (July 19, 2014) — Research on plaque from ancient teeth shows that our prehistoric ancestor's had a detailed understanding of plants long before developing agriculture. Video provided by Newsy
Powered by NewsLook.com
Contaminated Water Kills 3 Babies in South African Town

Contaminated Water Kills 3 Babies in South African Town

AFP (July 18, 2014) — Contaminated water in South Africa's northwestern town of Bloemhof kills three babies and hospitalises over 500 people. The incident highlights growing fears over water safety in South Africa. Duration: 02:22 Video provided by AFP
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:
from the past week

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