Navigation Links
Key found to breakthrough drug for clot victims
Date:3/10/2008

PORTLAND, Ore. A team of researchers at Oregon Health & Science University and Washington University in St. Louis have described for the first time the mechanism that gives a mutant enzyme molecule that they have engineered and patented the potential to become a breakthrough drug for treating heart attacks and strokes.

The team described how their genetically modified enzyme, called WE-thrombin, functions as a potent clot busting agent while retaining little of the power that thrombin, its non-engineered parent, has to cause the opposite result, a cascade of clot building. They did so in a paper published recently in Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB), a peer-reviewed journal of the American Heart Association. An editorial commentary in ATVB hailed this breakthrough as a significant advance in understanding the functions and antithrombotic potential of (WE thrombin) in particular, and the approach of using engineered human proteins more broadly

The successful development of WE-thrombin would be a major medical breakthrough in antithrombotic therapy, ultimately saving thousands of lives worldwide each year, said the lead investigator Andrs Gruber, M.D., Ph.D., associate professor of medicine in the division of hematology and medical oncology, OHSU School of Medicine.

Thrombin is an enzyme that, paradoxically, has the capacity both to promote and prevent blood clotting. Balancing the two depends on a highly complex system of positive and negative feedback loops. Normal blood clotting is vital to minimize bleeding in the event of an injury. Excessive clotting can lead to thrombosis, the blockage of a blood vessel.

Heart attacks and strokes most often the result of blood clots remain two of the three leading causes of death and severe disability in the United States. The toll from these diseases persists at high levels in part because the drugs now relied on to stop or break up clots such as heparin or TPA, tissue plasminogen activator pose the risk of triggering hard-to-control systemic bleeding. Also, they cant be injected outside of a clinical setting in patients that present with symptoms of stroke or heart attack and, even then, only after time consuming preliminary diagnostic tests and scans. Every minute that treatment is delayed after the onset of a stroke or heart attack reduces the odds of survival or recovery.

The researchers contemplate that, if it is approved for use in humans, WE thrombin which the research team has demonstrated is effective and safe in large primates could safely be injected by paramedics or others, whenever someone displays the first symptoms and signs of a stroke or heart attack without fear of causing harm if the symptoms prove to be a false alarm.

Aronora LLC, a startup biotechnology company, has been formed by Gruber along with the primary co-investigators and others, to seek financial support for preclinical and early clinical development of WE-thrombin as a safe alternative to existing antithrombotic drugs. The market for such drugs is estimated to exceed $20 billion per year worldwide. The patents on WE-thrombin are currently co-owned by the investigators parent institutions, OHSU, Emory University and Washington University.

WE-thrombin is the most potent antithrombotic agent that ever has been described, said Gruber. And thats because of its specificity. It effectively utilizes a natural drug delivery system of circulating blood platelets and white blood cells that accumulate in the clot formation process to deliver its punch directly to a blood clot. The process parallels that of targeted drug delivery. Its effective inside a blood vessel, but not at all effective outside the blood stream, which is exactly what you want from an antithrombotic agent.

What weve done recently, added coinvestigator Owen J.T. McCarty, Ph.D., is located the exact point where the catalytic reaction takes place in vivo that makes this molecule work as a superior antithrombotic agent. McCarty, an expert in platelet biology, is assistant professor of biomedical engineering in the department of cell and developmental biology, OHSU School of Medicine.

Blood platelets are small cells that sense an injury and rush to form a clot to reduce bleeding. They do so by binding thrombin, which cuts fibrinogen into strands of fibrin to form the glue of a clot. The process becomes self sustaining, or autocatalytic, which means that the glue is produced and reproduced in a rapid chain reaction. Thrombin subsequently counterbalances the process by activating protein C inside the blood vessel, which shuts down the autocatalytic reaction in the blood stream.

WE-thrombin, the mutant form of thrombin, lacks the ability to create the glue but still can produce activated protein C (APC) inside the blood vessels, which makes it a unique, locally acting anticoagulant. The molecule enhances this ability, the research team discovered, by attaching itself to a receptor, or sticking point, called glycoprotein Ib (GPIb), located on the surface of platelets. In doing so, WE-thrombin shoulders aside and thus inhibits the protein (the von Willebrand factor) that promotes coagulation, which now has to compete for the same receptor on the platelets.

Because of WE-thrombins specificity and potency, the dosage required to be effective in humans, Gruber said, is expected to be less than 0.5 milligrams, and possibly less than 0.1 milligrams, or 200- to 1,000-fold less than the dosage levels of TPA commonly being administered now in heart attack and stroke.


'/>"/>

Contact: Harry Lenhart
lenharth@ohsu.edu
503-494-8231
Oregon Health & Science University
Source:Eurekalert

Related medicine news :

1. Lupus Foundation to Host Community Outreach Initiatives
2. National Patient Safety Foundation Proposes Universal Patient Compact
3. United Mitochondrial Disease Foundation Statement on Vaccines, Autism and Mitochondrial Disease
4. Founding Father of Modern Cosmetic Dermatology Seeks to Warn Public of Misrepresented Data and Inappropriate Use of Botox
5. Lupus Foundation of America Webchat to Discuss Kidney Disease in Lupus
6. Zounds Hearing Enters Moorestown and Announces $225,000 Hearing Partnership With Twilight Wish Foundation
7. Whole Planet Foundation(TM) (a Whole Foods Market Foundation) and Nobel Peace Prize Winner Dr. Muhammad Yunus Partner With Natural Foods Vendors, Pledging Over $1 Million to Help Combat Poverty
8. Childrens Burn Foundations Benefit Raises More Than $875,000 for Burn Survivors and Prevention
9. Cultivating the Smart Patient: Author and RealAge Founder Michael F. Roizen, MD to Present Keynote at URAC Conference
10. White Hat Brands, Juvenile Diabetes Research Foundation Offer the Juice on New Partnership
11. Inaugural Bowen Foundation Run/Walk to Fight Autism in Maryland Set for Saturday, March 29
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/21/2017)... ... January 21, 2017 , ... Northern California Medical Associates (NCMA) ... their multi-specialty medical group. The dermatology practice provides general dermatologic treatment, outpatient surgery, ... add this excellent dermatology practice to our group’s medical services,” explains NCMA CEO, ...
(Date:1/21/2017)... ... ... In the United States, 20 million women and 10 million men suffer ... shame for having struggled with an eating disorder as well as common co-occurring conditions ... Life After an Eating Disorder” -- to be featured at this year’s iaedp Symposium ...
(Date:1/20/2017)... (PRWEB) , ... January 20, 2017 , ... Spectrum Aquatics Launches New ADA Portable Motion ... deck space. Since the lift is mounted on wheels, it can be wheeled out of ... down kit, to fasten to the deck. "We have transformed the feedback from customers into ...
(Date:1/20/2017)... Abilene, Texas (PRWEB) , ... January 20, 2017 , ... Yisrayl Hawkins, Pastor and Overseer ... back the bible in homes across the world. Yisrayl says this generation is a time ... better is to turn to the Bible. , Yisrayl says he does not want to ...
(Date:1/20/2017)... ... January 20, 2017 , ... Doctor C LLC, a company based ... ECRM trade show to continue the marketing and distribution of its product, The Right ... providing 400 percent better absorption than traditional vitamin C supplements. At the trade show, ...
Breaking Medicine News(10 mins):
(Date:1/19/2017)... 2017 Many patients don,t realize that they ... a pharmacy just a few blocks away charges only ... problem Medicationdiscountcard.com has created a price comparison ... much their medication will cost at most nearby pharmacies. ... Medicationdiscountcard.com takes all of the ...
(Date:1/19/2017)... Accuray Incorporated (Nasdaq: ARAY ) ... to set the bar for excellence in customer satisfaction. ... satisfaction rating among radiation treatment delivery systems in the ... Intelligence Briefing™. The most recent ratings trend also shows ... peers for 11 of the past 12 quarters. ...
(Date:1/19/2017)... , Jan. 19, 2017 ViewRay, Inc. (Nasdaq: ... federal institution supporting research in Germany ... patient treatments at the University Clinic Heidelberg as part ... The MRIdian Linac program will be headed by Medical ... heads radiation oncology at the German Cancer Research Center ...
Breaking Medicine Technology: