Researchers at the University of Alberta pioneer gene therapy to restore alveoli and lung capillaries in damaged rat lungs; first step in one day helping premature babies.

Premature babies are often at risk of developing bronchopulmonary dysplasia -- a chronic lung disease caused by having to place the tiny infants on ventilators and oxygen-rich therapy for acute respiratory failure.

Using animal models, Thébaud and a team of University of Alberta researchers have taken what they say is the first important step towards a treatment -- in effect, growing new blood vessels and alveoli – the tiny air sacs where gas exchange occurs between the lungs and blood vessels -- in tiny rat lungs.

The results of their work were recently published in Circulation.

The results have caused a stir in the scientific community: in an accompanying editorial in the journal, Kurt Stenmark, a University of Colorado Divisions of Critical Care and Pulmonary Medicine researcher, said the studies "…raise new possibilities for the treatment of infants with severe chronic lung disease. It seems possible that by augmenting or restoring vascular growth, overall lung growth and ultimately lung function can be restored."

Doing that involved a new gene therapy technique, explains Thébaud. Knowing that a particular protein, VEGF, a vascular endothelial growth factor, is crucial for the normal development of the lung, and that angiopoeitin-1, another angiogenic growth factor is crucial for blood vessel maturation, the team attached the proteins to an adenovirus and administered it through an aerosol directly into the lungs. In effect, the virus carried the protein to the heart of millions of lung cells. Once inside the cells, the growth factor proteins went to work doing the job they were programmed to do.

The results were striking: in microscopic images, the scientists have charted the growth of alveoli and lung capillaries. In a typically healthy lung, a complex network of capillaries encircles the alveoli. Oxygen flows from the lungs through ultra-fine epithelial and endothelial tissues into the blood; carbon dioxide diffuses from the blood into the alveoli. In an infant's underdeveloped lungs, the alveoli are larger and fewer and there are fewer developed capillaries. It's a condition that leaves them gasping--and one that is shared by people who have emphysema.

The next step is to prove it's possible to replicate safely in larger mammals. Once that's done, it's possible the concept -- growing blood vessels to cure a disease that is traditionally thought of as an airway disease -- could be tested clinically in people.

Source: University of Alberta, 2005


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