Protein Found That Complicates Healing from Respiratory Infections

A protein has been identified that slows healing of respiratory tissues and complicates recovery from diseases such as influenza and pneumonia.

Investigators at Nanyang Technological University (Singapore) had found by examining human lung biopsy specimens from patients with infection-induced pneumonia with tissue damage that expression of the ANGPTL4 (angiopoietin-like 4) gene was elevated as compared to normal lung samples. ANGPTL4 was known to enhance pulmonary tissue leakiness and exacerbate inflammation-induced lung damage.

To counter the effects of ANGPTL4, the investigators developed a neutralizing antibody that blocked the activity of the protein. In addition they worked with a line of mice that had been genetically engineered to lack the ANGPTL4 gene.

Results published in the February 10, 2015, issue of the journal Cell Reports revealed that treatment of infected mice with neutralizing anti-ANGPTL4 antibodies significantly accelerated lung recovery and improved lung tissue integrity. ANGPTL4-deficient mice also showed reduced lung damage and recovered faster from influenza infection when compared to their wild-type counterparts.

"We know that ANGPTL4 usually helps to regulate blood vessel leakiness. But this is the first time we have shown that by blocking this protein, we are able to control the natural response of inflammation, which in turn reduces the damage that inflammation does to the lungs," said senior author Dr. Andrew Tan Nguan Soon, associate professor of biological sciences at Nanyang Technological University. "When the antibody we developed was given to mice suffering from pneumonia and influenza that had high levels of ANGPTL4, these mice recovered much faster than the other mice which did not receive the antibodies. The concentration of ANGPTL4 correlates to the amount of inflammation the patient is having."

"While it will take up to eight years to develop the antibody into a useable treatment for human patients, we are currently developing a diagnostic kit which should be commercialized in about three years," said Dr. Tan. "The kit will help doctors diagnose the severity of pneumonia and the efficacy of the prescribed treatment. This is done by detecting the concentration of a particular protein called ANGPTL4, which is present in samples taken from patients suffering from upper respiratory tract infections. With our diagnostic kit, doctors will be able to see if a particular treatment is working for a patient. This is done by observing whether the concentration of ANGPTL4 is decreasing or not."

Two multi-national biotechnology corporations, Abcam (Cambridge, United Kingdom) and Adipogen (San Diego, CA, USA), have been awarded the rights to produce and market the patent-pending anti-ANGPTL4 antibody.

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Nanyang Technological University
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