Featured Research

from universities, journals, and other organizations

Ancient DNA Helps Researchers Unearth Potential Hemophilia Therapy

Date:
February 27, 2006
Source:
University of Florida
Summary:
Using a dormant strand of DNA that has quietly existed in fish for millions of years, the researchers replaced the faulty gene responsible for hemophilia in neonatal mice.

GAINESVILLE, Fla. - A cut can be life-threatening for people with hemophilia, whose bodies don't produce enough of a protein that prevents prolonged bleeding.

Now University of Florida researchers may be one step closer to finding a safe way to spur production of this missing protein in patients with the most common form of the hereditary bleeding disorder. Using a dormant strand of DNA that has quietly existed in fish for millions of years, the researchers replaced the faulty gene responsible for the disease in neonatal mice, according to findings published online this month in the journal Molecular Therapy.

"The degree to which these patients have problems from hemophilia stems from how much of this protein, factor VIII, is missing," said Bradley Fletcher, M.D., Ph.D., a UF assistant professor of pharmacology and one of the lead authors of the study. "If they have very low levels of it, they have lifelong problems of bleeding, but what's even more problematic for them is they bleed into their joints, knees, hips and ankles, which limits their mobility."

Although hemophiliac mice don't develop some of these more extreme symptoms of the disease, gene therapy prevented profuse bleeding in the animals, the findings show.

More than 18,000 Americans, nearly all men, have hemophilia A, the most common form of the disease, according to the Centers for Disease Control and Prevention. Currently, the only safe treatment for the disorder is a purified form of the protein, but it can cost patients thousands of dollars and its effects don't last long. Scientists have been trying to find a safe way to perform gene therapy in hemophilia patients for years, but problems with the viruses typically used to transport needed genes to their target destinations have stymied their success, Fletcher said.

Researchers usually hide corrective genes inside viruses, which then infect cells. Without the virus to act as a key, the gene would be unable to enter the cell. But viral gene therapy has been associated with medical complications, and a few human patients have died as a result.

Instead, UF researchers used a novel nonviral approach, employing a strand of DNA present in modern-day fish called a transposon to transport the gene directly into the DNA of the mice. Nonviral therapy is thought to be safer, Fletcher said.

Transposons have the natural ability to bounce to different positions in DNA, allowing them to chauffeur genes into the cell. The transposon UF researchers used is one of a few that work in mammals, but until University of Minnesota scientists discovered it in 1997, it had remained hidden in the DNA of fish like trout for 15 million years. Years of mutations in the genetic code had buried the transposon, silencing its ability to issue molecular marching orders.

Fletcher and researchers Li Liu, M.D., Ph.D., an adjunct postdoctoral associate in the department of pharmacology and therapeutics, and Cathryn Mah, a UF assistant professor of pediatric cellular and molecular therapy, used the transposon to inject the gene into endothelial cells, which line blood vessels and other parts of the body. This was unique, Fletcher said, because the liver is generally considered the body's powerhouse for producing the protein needed to keep hemophilia at bay. The study showed that these endothelial cells also can produce enough protein to correct the problem, he said.

"I think endothelial cells are potentially a very important cell to make factor VIII," said Katherine P. Ponder, M.D., an associate professor of medicine and a hemophilia researcher at Washington University in St. Louis. "They're a very attractive cell type to express it."

It also was the first time researchers attempted such an approach on an animal so young. In adult mice, the immune system normally views clotting protein as an invader and rejects it after traditional gene therapy. But UF researchers bypassed this immune response by performing gene therapy on mice within 24 hours of their birth, when their immune systems were still naive and would accept the protein.

This type of approach cannot be used in human babies yet because doctors have no way of gauging how severe hemophilia is in newborns. Patients with mild disease will have fewer problems and the benefits of gene therapy may not outweigh risks to the baby, Fletcher said.

Ponder said she thinks the technique also may prove to share some of the same problems as viral-based gene therapy, potentially activating cells that cause cancer.

Now UF researchers are studying different ways to use the transposon and trying to find a way to overcome the immune attack when performing gene therapy on adult animals.

"I don't think the research is done," Mah said. "But this is definitely a step forward for hemophilia gene therapy."



Story Source:

The above story is based on materials provided by University of Florida. Note: Materials may be edited for content and length.


Cite This Page:

University of Florida. "Ancient DNA Helps Researchers Unearth Potential Hemophilia Therapy." ScienceDaily. ScienceDaily, 27 February 2006. <www.sciencedaily.com/releases/2006/02/060227184747.htm>.
University of Florida. (2006, February 27). Ancient DNA Helps Researchers Unearth Potential Hemophilia Therapy. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2006/02/060227184747.htm
University of Florida. "Ancient DNA Helps Researchers Unearth Potential Hemophilia Therapy." ScienceDaily. www.sciencedaily.com/releases/2006/02/060227184747.htm (accessed July 28, 2014).

Share This




More Health & Medicine News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com
West Africa Gripped by Deadly Ebola Outbreak

West Africa Gripped by Deadly Ebola Outbreak

AFP (July 28, 2014) The worst-ever outbreak of the deadly Ebola epidemic grips west Africa, killing hundreds. Duration: 00:48 Video provided by AFP
Powered by NewsLook.com
Trees Could Save More Than 850 Lives Each Year

Trees Could Save More Than 850 Lives Each Year

Newsy (July 27, 2014) A national study conducted by the USDA Forest Service found that trees collectively save more than 850 lives on an annual basis. Video provided by Newsy
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