Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel gene therapy may lead to cure in hemophilia A patients

05.07.2006
Even hard to treat subset requiring expensive treatment

A discovery by Medical College of Wisconsin and BloodCenter of Wisconsin researchers in Milwaukee may be a key to a permanent genetic cure for hemophilia A patients, including a subset who do not respond to conventional blood transfusions. The study of genetically altered hemophilia mice is published in the July 2006 edition of The Journal of Clinical Investigation.

Hemophilia A affects about one in 5,000 males who lack the hereditary blood clotting protein, Factor VIII (FVIII). Traditional treatment requires infusion of synthetic FVIII two to three times a week to control bleeding episodes. However, about 30 percent of these patients develop antibodies to FVIII, selectively inactivating its clotting properties and negating its therapeutic role. Treatment for adults who have these inhibitory antibodies can cost over $1 million annually if there is a major bleeding episode.

"We developed a Trojan horse approach cloaking FVIII in a platelet so that it is undetected by the antibodies and its clotting properties are preserved until the platelet sticks to a damaged blood vessel and releases its stored protein which now includes FVIII.," explains senior author Robert R. Montgomery, M.D., senior investigator at the BloodCenter of Wisconsin and professor of pediatric hematology at the Medical College. He is also affiliated with the Children's Research Institute.

"This is truly a landmark development for hemophilia A patients," says hematologist, Joan Gill, M.D., professor of pediatric hematology at the Medical College, and director of the Comprehensive Center for Bleeding Disorders at the BloodCenter and Children's Hospital of Wisconsin. "We look forward to the day when basic research is completed and clinical trials can begin in patients."

Normally in an injury, platelets circulating in plasma - the liquid portion of the blood - stick to the site of the blood vessel wound, activating its surface and rapidly stopping bleeding. In hemophilia patients, infusion of FVIII replaces the missing clotting factor and enables normal cessation of bleeding. However, some 30 percent of patients see the FVIII as a foreign protein and mount antibodies to destroy it, rendering the FVIII treatment useless.

Newer FVIII treatment products that bypass this attack can run into $10,000 or $100,000 per treatment episode and costs for a patient may exceed $1 million annually. So far attempts at gene therapy for a permanent cure have not been successful.

According to the lead author, Qizhen Shi, M.D., Ph.D., an American Heart Association supported postdoctoral fellow, "Our team of scientists have developed an approach in mice that not only could make gene therapy successful for patients with hemophilia who don't have antibodies, but more importantly can be used to treat patients with antibodies.

"To get around the antibody attack on FVIII which occurs readily in plasma, we inserted a gene into a blood stem cell so that FVIII is produced and stored in blood platelets, hidden from view and attack, ready to release when a blood vessel is damaged, quickly enabling normal clotting before the antibodies can begin their attack. Our approach was very effective even in mice treated with five to ten thousand times the amount of antibody that would normally prevent treatment of a hemophilia patient with FVIII."

The new method will next be tested in larger animal models before clinical trials can begin in patients. Blood and bone marrow stem cells would be harvested from hemophilia patients in much the same way they are collected from bone marrow donors. A non-replicative virus containing the FVIII gene would be introduced into the stem cells from the patient. The FVIII engineered for production only in platelets would insert itself into the DNA of the stem cells. These same stem cells would then be given back to the donor patient and the stem cells would continue to make blood cells normally, releasing the life saving FVIII only when the platelets stick to a bleeding site of injury.

"This process would last for the rest of the patient's life and will work regardless of whether antibodies are present or absent," says Dr. Montgomery. "There will be many more studies needed to apply this approach in patients but this treatment could normalize bleeding for patients with hemophilia.

"What is most exciting about this first design of gene therapy for hemophilia is that it works not only for routine hemophilia but also for the 30 percent of patients who have developed inhibitory antibodies that make normal replacement treatment impossible," Dr. Montgomery concludes.

Toranj Marphetia | EurekAlert!
Further information:
http://www.mcw.edu

More articles from Life Sciences:

nachricht Water world
20.11.2017 | Washington University in St. Louis

nachricht Carefully crafted light pulses control neuron activity
20.11.2017 | University of Illinois at Urbana-Champaign

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Antarctic landscape insights keep ice loss forecasts on the radar

20.11.2017 | Earth Sciences

Filling the gap: High-latitude volcanic eruptions also have global impact

20.11.2017 | Earth Sciences

Water world

20.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>