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Facing down the super-antigens

Posted By ISRAEL21c Staff On August 2, 2009 @ 4:03 am In | No Comments

An Israeli biotech company is developing a new peptide that could be used to treat sepsis and septic shock by preventing a cascade of toxic super-antigens in the body.

Massive infection, autoimmune disease and even toxic shock resulting from bio-weapons are all on their way to becoming treatable conditions, according to six-year-old Israeli biotechnology company, Atox Bio.

It has others convinced, as well. Late June, the company entered into an agreement with US contract research organization Fast-Track Drugs & Biologics to continue development of its new class of therapeutics.

Fast-Track, which is based in Maryland, works in the private sector in the US, Israel, and Japan, as well as with the federal sector in the US. The collaboration includes pre-clinical studies and Phase 1 clinical trials at the University of Maryland in Baltimore, and $575,000 in research funding from the Israel-US Binational Industrial Research and Development Fund (BIRD).

Severe sepsis and septic shock cause about 215,000 deaths in the US alone every year. They are the second leading cause of death in non-coronary intensive care units, according to the Centers for Disease Control and Prevention. Mortality rates are high, ranging from 20 percent of all patients for sepsis, 40% for severe sepsis, and 60% for septic shock.

Sepsis occurs when a person gets an infection, and the body mounts an excessive systematic inflammatory response. In effect, it is the body’s own immune system that causes most of the symptoms of sepsis. Severe sepsis can lead to damage to the brain, lungs, heart, kidneys and liver, low blood pressure, and insufficient blood flow to organs. Septic shock is the most severe form of sepsis and it can lead to complete organ failure.

Subverting the immune system

At the heart of Atox Bio’s breakthrough technology is a new understanding of how certain lethal toxins in the body subvert the immune system. Known as super-antigens, these toxins are produced by common bacteria such as staphylococcus and streptococcus. More than 40 divergent super-antigens have thus far been recognized.

Atox Bio scientific co-founders, biochemist and molecular biologist Dr. Raymond Kaempfer and molecular immunologist Gila Arad of the Hebrew University of Jerusalem, discovered that these super-antigens elicit an immune response up to 50,000 times more powerful than that induced by ordinary antigens.

This results in a storm of certain molecules (Th1 cytokines) which wreak havoc on the immune system. Among the mayhem this storm sets off are sepsis and septic shock; as well as over 80 crippling autoimmune diseases, from multiple sclerosis to rheumatoid arthritis; increased vulnerability to lethal influenza viruses, among them swine and avian flu; and toxic shock wrought by bio-weapons.

This deadly mechanism of the super-antigens has been deciphered by Atox Bio’s scientists, who then went on to find a way of stopping the toxic cascade before the Th1 cells are even activated. The company’s technology platform uses a peptide it designed (a short stretch of protein known as AB103) to block this harmful reaction, halting the toxins and leaving a normal immune response.

In animal studies, Atox Bio’s peptide has been found to protect and rescue from lethal toxic and septic shock. More than that: once protected, the survivors were immune to further toxin challenges.

US Army and Defense support

It was with this core technology that Atox Bio spun off from Yissum, the technology transfer company of the Hebrew University of Jerusalem, in 2003. Registered in Delaware as a privately held US company, Atox Bio’s R&D is conducted by its wholly owned Israeli subsidiary, Atox Bio, in Jerusalem.

In its six years of life, the company has received over $12 million in US federal grants – including over $6.5 million from the US Army and the US Defense Advanced Research Projects Agency (DARPA), and more than $5.6 million from the National Institutes of Health, one of the largest such sums ever awarded outside the US.

The joint program that Atox Bio entered this summer with Fast-Track Drugs & Biologics, which provides strategic planning, clinical trial and regulatory support services to the pharmaceutical and biotech industries for the development of vaccines and drugs, will continue development of Atox Bio’s novel peptide, AB103.

No date has yet been set to begin clinical trials, but if they prove a success in treating sepsis, and manage to prevent the superantigen storm from happening, the peptide could also at a later date be adapted to treat autoimmune diseases as well.

In a statement, Atox CEO Uri Danon said that he was confident that this collaboration, which “combines Atox Bio’s breakthrough technology, the proven regulatory and clinical management capabilities of Fast-Track and the University of Maryland School of Medicine’s strong clinical capabilities” will spur development of Atox Bio’s groundbreaking superantigen antagonist technology and the creation of a new class of therapeutics which will answer a vital and as yet unmet medical need.

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