Arriva Pharmaceuticals announced that it would present new data on the company's lead molecule, recombinant Alpha 1-Antitrypsin (rAAT)- that rAAT successfully prevented up to 73 per cent of the lung tissue breakdown caused by cigarette smoke in treated animals-at the European Respiratory Society (ERS) Meeting in Glasgow next week.
Data to be presented will demonstrate that rAAT, delivered via inhalation to the lungs of smoking mice normalized inflammatory cell recruitment to the lung and prevented airspace enlargement compared with untreated animals (71%, 73% and 42% reduction in alveolar damage respectively for low, mid and high doses).
"Since the mouse model is widely recognized as reproducing most characteristics of the disease as it occurs in humans, this study gives rise to the hope for a clinical treatment," said Steven Shapiro, Professor of Medicine, Harvard Medical School, an expert in the use of animals to model human emphysema.
The release says, in the typical course of COPD progression, the body responds to the presence of foreign substances in the lungs - caused by the inhalation of smoke and/or toxins in the air - by triggering white blood cells to accumulate and eliminate the 'invaders'. If the cycle is unchecked, neutrophil elastase, a protease released by the white blood cells, builds up and irreversibly damages the alveoli (tiny air sacs in the lungs). Over time the alveoli become damaged and can no longer effectively handle the exchange of carbon dioxide for oxygen.
Data from the smoking mouse model study conducted in conjunction with the Brigham and Women's Hospital in Boston, MA and Washington University in St Louis, MO suggest that low levels of inhaled rAAT may be able to significantly and naturally modify the decline in lung function that is the hallmark of emphysema. Alpha 1-Antitrypsin is a naturally occurring protein that neutralizes the effects of proteases in several organ systems, mainly the respiratory system. Unlike auxiliary treatments that serve to compensate temporarily for decreased lung function by dilating lung airways or reducing inflammation, Alpha 1-Antitrypsin therapy works at low levels to restore the normal 'protease/inhibitor' balance that is compromised in many respiratory diseases.
"For patients suffering from COPD and other respiratory diseases, whether the result of years of cigarette smoking or environmental factors, this is a positive first step that demonstrates that recombinant Alpha 1-Antitrypsin delivered directly to the lungs, may prevent progressive tissue damage," said Philip Pemberton, vice president of Research and Development, Arriva Pharmaceuticals, Inc.
In a related study announced in February, rAAT was tested in a phase I clinical trial and administered in a nebulized form to patients with Hereditary Emphysema. Results from the human trial evaluating the safety and immunogenicity showed that rAAT was well tolerated even at the maximum dose administered. Hereditary Emphysema is a rare genetic disease that deprives patients of adequate levels of circulating Alpha 1-Antitrypsin protein and leads to excessive inflammation, chronic emphysema and often, early death. Current therapy involves the intravenous infusion of plasma derived AAT but quantities are limited and large amounts are required to reach the lung. Baxter and Arriva are currently jointly developing a recombinant, nebulized form of Alpha 1-Antitrypsin for this indication.