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Archive - Jul 10, 2009

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Progress on Life-Saving Antibody for Inhalation Anthrax

The New England Journal of Medicine has published the results of two pivotal animal efficacy studies showing the life-saving potential of a human monoclonal antibody drug raxibacumab (ABthrax) in inhalation anthrax disease. The publication also included the results of human safety studies that supported the use of raxibacumab in the event of life-threatening inhalation anthrax disease. Raxibacumab is manufactured by Human Genome Sciences, Inc., which conducted the studies together with collaborators. "The results published today showed that a single dose of raxibacumab was highly effective as a treatment for inhalation anthrax in both rabbits and monkeys," said Dr. Sally D. Bolmer, senior author of the NEJM report and Senior Vice President, Development and Regulatory Affairs, Human Genome Sciences. "Raxibacumab acted quickly to provide a significant survival benefit to animals showing clinical signs of disease caused by exposure to a dose of aerosolized anthrax spores that was approximately 200 times the median lethal dose. We also note that the safety profile shown in healthy human volunteers provides support for use of raxibacumab in the clinical setting of immediately life-threatening inhalation anthrax disease." Raxibacumab represents a new way to address the anthrax threat. While antibiotics can kill the anthrax bacteria, they are not effective against the deadly toxins that the bacteria produce. Raxibacumab targets anthrax toxins after they are released by the bacteria into the blood and tissues. In an inhalation anthrax attack, people may not know they are infected with anthrax until the toxins already are circulating in their blood, and it may be too late for antibiotics alone to be effective.

Yeast Model May Aid Understanding of Friedrich’s Ataxia

Friedrich’s ataxia is one of the most common hereditary ataxias and its most common molecular cause is a massive expansion in the number of GAA triplet nucleotide repeats in intron 1 of the frataxin gene on chromosome 9. There is no cure for the condition which damages the nervous system and can cause heart disease. Until now, research has been hampered by the lack of an animal model in which the GAA triplet expansions could be replicated and studied. But in the July 10 issue of Molecular Cell, researchers report that they have created such a model in yeast. In doing so, the scientists were able to analyze GAA repeat expansions and then identify cellular proteins that thwarted normal replication and promoted the elongated sequence. "In essence, we believe that the replication machinery occasionally gets tangled within a repetitive run, adding extra repeats while trying to escape," said Dr. Sergei Mirkin, senior author of the study. “And the longer the repeat, the more likely the entanglement is. That is as if a car which entered a roundabout misses the right exit due the heavy traffic and has to make the whole extra circle before finally escaping.” Dr. Mirkin and his team carried out a genetic screen to identify yeast proteins affecting repeat expansions. They found that the proteins within the cell that are known to facilitate the smooth replication fork progression decreased repeat expansions. Meanwhile the proteins responsible for the fork deviations, such as template switching and reversal, increased repeat expansions. It is possible that study of the yeast model may illuminate molecular mechanisms underlying Friedrich’s ataxia and may point the way toward effective interventions.