Sunday, 24 April 2011

TUBERCULOSIS: Scientists identify enzyme that damages lungs of TB patients

Apr 22 2011, Scientists have identified a key enzyme responsible for destroying lung tissues in patients suffering from tuberculosis (TB), a discovery that could lead to new and effective treatment to prevent lung damage.
It's known that lung tissue of TB patients are damaged, causing them to cough up the bacteria, which then spread through the air and can be inhaled by others.
The mechanism behind this lung damage has been poorly understood, and no treatments are currently used to prevent it from occurring. TB patients require at least six months of antibiotic treatment, but drug-resistant strains of the bacterium are becoming increasingly common.
But, the new research -- by a team from the Imperial College London, the Columbia University in New York and the University of East Anglia -- showed that in patients with TB, there is an increase in levels of an enzyme, called MMP-1, in their lungs.
When the researchers, who detailed their findings in the 'Journal of Clinical Investigation', infected human immune cells with TB in the lab, they found that the cells greatly increased production of this enzyme.
Since the mouse version of MMP-1 is not expressed in the lung, the researchers developed a transgenic mouse with human MMP-1 to see whether the enzyme causes lung damage in Tuberculosis.
When these mice were infected with TB, MMP-1 levels increased significantly and the infection led to lung damage similar to that seen in humans with TB.
The scientists also found that a drug proven to be safe in humans was effective at suppressing MMP-1 activity driven by TB infection in human cells.
The findings suggested that similar drugs might prevent lung damage in TB patients and help limit the spread of the disease, the researchers said.
Dr Paul Elkington, from the Department of Infectious Diseases and Immunity at Imperial College London, said: "A third of the world's population is infected with tuberculosis, and almost 2 million people die from the disease every year.
"Standard Tuberculosis treatment has remained unchanged for 35 years, and no current treatments prevent the lung destruction that TB causes. These findings suggest that drugs available now might be able to reduce deaths from TB."
In 1990s, many MMP inhibitor drugs were developed because they showed initial promise for treating cancer. Now, the researchers plan to carry out further studies to see whether these drugs can prevent lung damage in TB patients.
Prof Jon Friedland, senior author of the study from the Department of Infectious Diseases and Immunity at Imperial College London, said: "Until now, we haven't had a convincing explanation of how lung destruction is caused by TB.
"We hypothesised that protease enzymes must be involved, since nothing else could break down the strong collagen fibres that make up the scaffold of the lung. The results of this study provide strong evidence to support that idea."

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