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Ever wonder how your blood miraculously stops flowing and forms a scab after a cut? Researchers have now pinpointed the mechanism down to the molecular level.
"The human body has an incredible ability to heal from life's scrapes and bruises," study co-author Wesley P. Wong, a principal investigator at the Rowland Institute at Harvard University, said in a university news release.
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"A central aspect of this response to damage is the ability to bring bleeding to an end, a process known as hemostasis," Wong said. "Yet regulating hemostasis is a complex balancing act."
If people have too much hemostatic activity, they can develop an excess of blood clots, resulting in thrombosis, which is a potentially deadly condition. On the other hand, if there is too little hemostatic activity, people could bleed to death, according to background information in the news release.
To achieve and maintain the right hemostatic balance, the body has a feedback system controlled by miniscule forces in the circulation system. The forces are applied to the highly-sensitive A2 domain of the blood-clotting protein called von Willebrand factor (VWF), which acts as a "force sensor," the researchers explained.
By manipulating single molecules, the researchers found that the tiniest force causes A2 molecules to unfold and lose much of their complex, three-dimensional organization. After the unfolding, the enzyme ADAMTS13 comes into play. The enzyme cuts the molecule, hence controlling the size of the blood clot, according to the study, in the June 5 issue ofScience.
"In the body, these cutting events decrease hemostatic potential and also enable blood clots to be trimmed in size," Wong said. "The system is so finely tuned that the A2 shear sensor is able to regulate the size of VWF within the bloodstream, maintaining the optimal size for responding properly to traumas."
To manipulate molecules, the researchers used "optical tweezers" developed in Wong's lab, which can apply miniscule forces to individual molecules while observing tiny changes in their length.
A better understanding of the mechanism of blot clotting could lead to new treatments for injuries or bleeding disorders, such as type 2A von Willebrand disease, the researchers noted.
As part of this collaboration, Angiotech has agreed to provide to Haemacure a senior secured bridge financing facility in the amount of
"Our new collaboration with Haemacure provides Angiotech with access to critically important technology for certain of our surgical product candidates currently in preclinical development," said Dr. William Hunter, President and CEO of Angiotech. "We believe we have assembled the majority of the key components necessary to deliver on the next generation of innovations, adding to our proprietary Quill SRS franchise for our surgical business, and we will provide additional details as we prepare certain of these product candidates for the clinical development and regulatory approval process.The collaboration will consist principally of the following three agreements:
- Fibrin Sealant Distribution Agreement. The parties have entered into a Distribution Agreement whereby Angiotech is granted non-exclusive,world-wide distribution rights to Haemacure's fibrin sealant product candidate in selected surgical indications. The distribution agreement has a term on a country-by-country and product-by-product basis of 10 years from the date Haemacure receives United States Food and Drug Administration (FDA) approval or similar regulatory approval in countries outside of the United States of its fibrin selant, and has an option for Angiotech to renew for an additional five years, subject to certain performance adjustments. Any fibrin sealant product would be marketed and distributed by Angiotech's surgical sales organization upon regulatory approval. Haemacure will be responsible for all clinical development and related costs with respect to fibrin sealant product candidates.
- Drug-Loaded Fibrin Sealant License and Development Agreement. The parties have entered into a License and Development Agreement whereby Haemacure and Angiotech have agreed to jointly develop and commercialize a next generation, drug-loaded fibrin sealant product candidate. Angiotech and Haemacure will collaborate to create novel fibrin sealant technologies that, in addition to the haemastatic properties offered by the fibrin sealant itself, may target the prevention of infection, pain, or delivery of stem cells using Haemacure's fibrin sealant as a carrier of such therapies. The companies will jointly conduct research and clinical development, with each party contributing key personnel, technology and intellectual property. Collaboration costs will be shared based on each company's contribution to the program, and eventual profits will be shared pro-rata based on each company's contribution to collaboration expenses. This term of the agreement will expire on a collaboration product-by-collaboration product basis upon the later of 15 years after the first commercial sale of such collaboration product, and the last-to-expire valid claim applicable to such collaboration product.
- Thrombin Supply Agreement. The parties have entered into an exclusive Supply Agreement whereby Haemacure will supply thrombin to Angiotech for the development of certain Angiotech preclinical product candidates that may require thrombin. The Supply Agreement has a term of 10 years from the first commercial sale of an approved Angiotech product containing thrombin procured from Haemacure, and has an option for Angiotech to renew for an additional five years. The senior secured bridge loan from Angiotech to Haemacure will provide US$2.5 million to Haemacure in multiple drawdowns. The loan will be senior to all of Haemacure's existing and future indebtedness, subject to certain exceptions; will bear interest at an annual rate of 10%, compounded quarterly and have a term of two years. Angiotech may, at its sole discretion, advance during a period of two years up to an additional US$1 million to Haemacure from time to time, in multiple draw-downs, for a total loan of US$3.5 million. The senior secured bridge loan also has certain equity conversion features and rights to board representation, as described in detail in Haemacure's press release dated May 22, 2009
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Taub founded Omrix Biopharmaceuticals Ltd. and led the company until it was sold to Johnson & Johnson (NYSE: JNJ) for $438 million in 2008. Following the sale, Taub said that he would seek new investment opportunities, and the investment in LifeBond is the first.
About Lifebond.
LifeBond is developing a series of next-generation biosurgical products which incorporate a proprietary adhesive platform that mimics the biochemical cross-linking cascade of late stage blood coagulation. The adhesive formulation forms a network similar to the fibrin network of blood clots but has demonstrated adhesive strength even greater than that of blood-derived fibrin sealants. LifeBond’s technology functions through the rapid and biocompatible in situ cross-linking of structural proteins. As they cross-link, proteins in the physiological environment undergo a process of gelation to form an adhesive hydrogel matrix. The properties of the cross-linking reaction and the hydrogel matrix can be controlled to fit a variety of applications.
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Tissuemed has already brought to market the TissuePatch product family of multilaminate absorbable surgical sealant films. These are a range of thin, synthetic, highly adherent films that act as a barrier to air, blood and other fluids encountered in surgery. More adherent than surgical glues, the films require no preparation and are effective within 30 seconds of contact. The technology demonstrated in these products has the ability to form the basis for new technologies or iterations of existing products. The Leeds based company is offering other companies the chance to benefit through a technology partnering initiative. The scheme, under the banner of Tissuemed Adhesive Biomaterials Technology Group, takes the form of a bespoke polymer design, synthesis and manufacturing programme that is open to third parties such as companies whose own medical devices could be enhanced by the incorporation of adhesive characteristics, surfaces or components. Examples of the types of surgical devices that may benefit from being self-adhesive to internal organs and structures include meshes, sutures and films as well as an array of implantable devices that may currently require physical means of anchoring. The programme offers companies and surgeons the chance to work with Tissuemed’s team of dedicated scientists to develop bespoke polymer designs and add new functionalities to their own products. It also offers support in a range of other areas including clinical and regulatory, physical and biochemical testing, intellectual property protection and sales and marketing expertise. Nick Woods, CEO of Tissuemed, comments, “In the same way that surgical staples revolutionised many surgical procedures in the eighties and nineties, we believe surgically effective adhesive compounds have the capability to drive advances in surgery in the foreseeable future.
"Evicel provides an effective means to stop oozing from small vessels during vascular surgery when suturing, compression or other standard techniques are not effective or practical," said Jesse Goodman, M.D., M.P.H., director of FDA's Center for Biologics Evaluation and Research.
This product is derived from pooled human plasma and consists of a fibrinogen concentrate and thrombin, two substances used to promote clotting. Both substances go through a two-stage process to reduce the risk of viral transmission in manufacturing, however, the potential risk for the transmission of blood-borne viruses cannot be totally eliminated.
In a pivotal study of 147 patients, the effectiveness of Evicel was compared with the standard bleeding control technique of applying pressure to a plastic covering (graft) placed over the open blood vessel. Eighty-three percent of those who received Evicel stopped bleeding within four minutes, compared with 39.7 percent in the control group.
Adverse events, such as anemia and graft site infection, were generally mild and occurred at about the same frequencies in the Evicel-treated group and the control group.
FDA originally licensed the predecessor of Evicel (Crosseal) in 2003 for use during liver surgery. Evicel is manufactured by OMRIX biopharmaceuticals LTD, Kiryat Ono, Israel.
Figures released by the Department of Health state that 802 haemophiliacs received blood from patients who went on to develop variant Creutzfeldt-Jackob Disease (vCJD).
It comes after a haemophiliac in his 70s was found to be infected with vCJD after his death. Although the infection was not the cause of his death, he had been treated with blood from a donor who later died from vCJD.
The disease, which destroyed Britain's beef industry in the mid 1990s, is believed to have been responsible for an estimated 164 deaths since 1995.
The Haemophilia Society has now called on the Government to test the patients at risk as soon as possible to determine whether they had contracted the disease.
Health officials released the figures in response to calls from Lord Morris of Manchester, who demanded to know whether the Government had revised its assessment of the risk presented by contaminated blood following the death of the haemophiliac who was found to be infected with vCJD.
Lord Darzi, Labour's health minister in the Lords, stated in a written answer to Lord Morris: "To date, 802 haemophilia patients are registered on the UK Haemophilia Centre Doctors' Organisation database as receiving clotting factors made from UK plasma pools containing a donation from a donor who went on to develop vCJD."
The Department of Health also revealed that 66 people who are not haemophiliacs have received blood components from donors who later went onto develop vCJD. Of these, 22 are still living, three died after contracting vCJD, and the others died from unrelated causes.
Chris James, chief executive of the Haemophilia Society, said: "We now know a much larger number of people have been exposed to higher-risk blood and blood product than was previously thought. vCJD remains an illness for which there is no test and no cure.
"It is just the latest in an increasingly long line of infections that people affected by bleeding disorders have been exposed to."
Haemophilia is a blood condition in which an essential clotting factor is missing and sufferers bleed for longer than normal. Around 6,000 people are affected by the condition within the UK.
Almost 4,700 haemophilia patients were infected with hepatitis C after receiving contaminated blood products that were given during the 1970s and 1980s. Campaigners have been fighting for compensation from the Government over the scandal.
The brain-wasting disease vCJD was first detected in the mid 1990s and since then most vCJD patients are thought to have been infected after eating BSE-contaminated meat.
The number of vCJD deaths peaked in 2000, when there were 28. That number has dropped to about five a year since 2005.
The epidemic of BSE in the 1980s and 1990s was caused by cattle being fed the remains of other cattle in the form of meat and bone meal, causing an infectious agent to spread.
More than four million cattle were slaughtered after almost 200,000 were infected with the fatal neurodegenerative disease.
Scientists recently warned that Britain could see a second wave of vCJD, affecting as many as 300 people, after discovering that genetic differences can affect how long it takes a person to incubate the disease.
