A new drug could save hundreds of thousands of people worldwide from limb amputations and death each year.
by Judy Siegel-Itzkovich
It is an ironic fact that the same number of people who go to hospitals to have infections treated catch new infections in the hospitals themselves. The widespread existence of bacteria in hospitals that are resistant to antibiotics and prey on patients with weak immune systems is responsible for the phenomenon known as toxic shock.
In this condition, the weakened patient is overwhelmed by the virulent bacteria, which multiply rapidly and cause pneumonia and organ failure so fast that doctors often have no time to identify the cause and fight it with effective drugs. In Israel alone, there are 400 cases of toxic shock every year, with 15 to 25 percent of these resulting in death, and many others in lost limbs, "eaten up" by the spreading toxins.
Aside from the many thousands of cases of toxic shock resulting from in-house hospital infections, the condition is common in those people with weak immune systems who suffer from food poisoning. Toxic shock has also been reported as the result of the improper use of tampons.
Toxic shock results from poisons produced by staphylococcal and streptococcal bacteria, which activate immune cells, known as T cells. These T cells introduce molecules called cytokines, which induce the condition. But now a team of Jerusalem scientists, headed by Professor Raymond Kaempfer, a molecular virologist at the Hebrew University-Hadassah Medical School, has designed a synthetic molecule called an "antagonist" that has been proven to successfully block the toxins ability to activate T cells in laboratory mice.
Pharmaceutical companies and their medical researchers around the world have spent hundreds of millions of dollars on fruitless attempts to deal with toxic shock, their attempts to "mop up" the harmful proteins hampered by the extremely high level of cytokine molecules produced in the body following introduction of a toxin.
Prof. Kaempfer and his team decided to focus on blocking the "toxicity cascade" before T cells are activated. They believe their P-12 peptide (named for the 12 amino acids that make it up) can be the first weapon against the virulent strains of bacteria that produce toxic shock. After exposing mice to a range of toxins, the injections of the peptide not only saved all of them from death and disease, but also the lives of about half of those rodents in which the process of toxic shock had already begun. The team is now working to develop a preventive vaccine, in addition to a peptide injection for treating people exposed to bacterial toxins.
Clinical human trials planned in several Israeli medical centers next year will be funded by the U.S. Defense Department, which is eager to use the drug for preventing deaths and limb amputations of soldiers and civilians exposed to deadly toxins in bacteriological warfare.
Because the patented protein molecule is simple and relatively cheap to produce, and has shown no harmful side effects, such a drug could be given safely to emergency-room patients showing the first symptoms of toxic shock. It could also be used to prevent massive organ failure in immune-compromised patients with pneumonia or AIDS, suggests Prof. Kaempfer, whose research conducted with colleagues Dr. Gila Arad, Revital Levy and Dalia Hillman, was published recently in the prestigious British medical journal Nature.