GlaxoSmithKline Finds Compound That Could Help Fight 'Superbugs'

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drugsGlaxoSmithKline (GSK) researchers announced Wednesday that they have found a new compound that may help in the fight against drug-resistant bacteria. The findings could ultimately assist scientists in developing new antibiotics to tackle what has been called one of the world's most pressing public health problems. Last year, a report from the American Academy of Microbiology called antibiotic resistance "an international pandemic," adding that "resistance essentially is uncontrollable."

Increased use of anti-bacteria drugs over the past 70 years has caused many microbes (bacteria, fungi, parasites and viruses) to develop resistance to antimicrobial drugs. As a result, almost every type of bacteria has become stronger and less responsive to antibiotic treatment, and infectious diseases are increasingly difficult to treat.

Few Weapons Against Superbugs

Meanwhile, the number of available antibiotics is declining because many can no longer combat common diseases, such as tuberculosis, and there's a dire shortage of alternatives. Drug-resistant superbugs like Methicillin-Resistant Staphylococcus Aureus (MRSA) can't be stopped by traditional antibiotics, making penicillin and its derivatives increasingly obsolete.

Yet, Big Pharma hasn't put much effort and research dollars into the problem. The London School of Economics and Political Science warned about the lack of antibiotic research. Bloomberg reports that just three antibiotics have been cleared for sale by U.S. regulators in the past five years.

So it's not surprising that the Glaxo announcement generated quite some excitement. Glaxo said it captured a snapshot of a new compound, called GSK 299423, latched onto a certain enzyme in bacteria. Stopping this enzyme prevents the bacteria from reproducing.

Medicines, such as the quinolone group of drugs (an example is Bayer's Cipro), target the enzyme and have been successfully used as antibiotics since 1962. Even though bacteria are increasingly developing resistance to this class of drugs, the new experimental compound attaches to the enzyme in a different place to quinolones, enabling it to stop the same quinolone-resistant bacteria. The compound was potent on MRSA strains and gram-negative bacteria like E. Coli.

Long Road Ahead

The research, published in Nature, is the result of two collaborations between GSK, the Wellcome Trust's Seeding Drug Discovery initiative and the U.S. Defense Threat Reduction Agency.

"We already knew that targeting this enzyme was clinically proven to stop bacteria in their tracks, we just needed to be a bit more inventive in how we attacked it," said Michael Gwynn, from GSK's Infectious Diseases research group.

Ted Bianco of the Wellcome Trust said: "This is an important step forward in the race against antibiotic resistance. By solving the new structure of this important bacterial enzyme, and understanding how these drugs work, the team has opened the door for targeted drug design of new antibiotics, which are urgently needed."

But while the study may give hope, the road ahead is long. First, scientists have to be able to develop a medicine from the compound, and only then can they begin early stage trials in humans. It's therefore far too early to predict future sales, but Bloomberg gives examples of two of the top-selling antibiotic brands: Pfizer's (PFE) Zyvox, which generated $1.1 billion in sales last year, and Cubicin, from Cubist Pharmaceuticals (CBST), which sold $538 million.

Rising Toll

New anti-bacteria drugs to combat the resistant superbugs couldn't come soon enough as the human and financial toll has been increasing. Between 5% and 10% of all hospital patients develop a drug-resistant infection, driving annual U.S. health-care costs up by about $5 billion, according to the NIH, as such patients are more likely to have longer hospital stays and may require more complicated treatment. And $1.1 billion is spent annually on unnecessary adult upper respiratory infection antibiotic prescriptions, according to the Centers for Disease Control and Prevention.

About 90,000 patients infected with drug-resistant bacteria die each year in the U.S. as a result of their infection, up from 13,300 patient deaths in 1992. Worldwide, bacterial and parasitic diseases are the second-leading cause of death.
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