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Potential Therapeutic Target for Lung Diseases Identified

by VR Sreeraman on October 18, 2009 at 1:46 PM
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 Potential Therapeutic Target for Lung Diseases Identified

Scientists from Washington University School of Medicine in St. Louis, McGill University have identified a genetic mutation that might open avenues for developing novel treatments for children born with lung distress and chronic obstructive pulmonary disease (COPD).

In the study, Dr Elaine C. Davis, senior author and associate professor of anatomy and cell biology at McGill University in Montreal, Canada compared various tissues from a mouse genetically engineered to be missing a form of the LTBP4 gene with skin tissue samples from one of the children.

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The children recruited in the study were born with abnormally developed lungs, gastrointestinal and urinary systems, skin, skull, bones and muscles.

In addition, all had cutis laxa, an inherited connective tissue disorder that causes skin to hang loosely from the body. Three of the patients died from respiratory failure before age 2.
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Dr Zsolt Urban, a pediatric geneticist at Washington University School of Medicine sequenced the LTBP4 gene in the four children and confirmed they had mutations.

He determined that the patients were the first described to show severe symptoms of a novel syndrome, which the researchers have named Urban-Rifkin-Davis Syndrome.

The findings have potential implications for newborns with underdeveloped lungs as well as older patients with severe lung diseases, including COPD, says Urban.

"Many newborns commonly have breathing difficulties," he said.

"Part of the problem is that the lung is not developed properly, especially the alveoli, the tiny sacs at the end of the smallest airways that serve as a place for oxygen uptake and gas exchange. This finding helped us identify a gene essential for the development of alveoli and potentially provide a target for intervention in premature babies," he added.

Urban said that potential treatments could include introducing the protein product of the LTBP4 gene to the newborn or using existing drugs that can moderate transforming growth factor beta (TGF_), which is overactivated in the tissues of these children.

The drug losartan, now in trials for treating Marfan syndrome, another connective tissue disorder, has been shown to limit TGF_ and merits further research as a possible treatment.

The study appears in the American Journal of Human Genetics.

Source: ANI
SRM
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