New Strategies in Drug Development Focusing on the Anti-Protease- Protease Balance in Alpha-1 Antitrypsin Deficiency

Title:New Strategies in Drug Development Focusing on the Anti-Protease- Protease Balance in Alpha-1 Antitrypsin Deficiency

Volume: 9 Issue: 4

Author(s): Emer P. Reeves, Sonya Cosgrove, David A. Bergin, Catherine M. Greene and Noel G. McElvaney

Affiliation:

Keywords: Alpha-1 antitrypsin; alpha-1 antitrypsin deficiency; protease imbalance; replacement therapy; gene therapy.

Abstract: Alpha-1 antitrypsin (AAT) is the most abundant proteinase inhibitor within the circulation and AAT deficiency is a genetic disorder characterised by serum levels of less than 11μmol/L. The Z mutation is the most common AAT allele associated with the disease and causes the most severe plasma deficiency, as the mutant protein polymerizes and accumulates within the endoplasmic reticulum of hepatocytes. The retained polymers are associated with cirrhosis and reduced serum levels of AAT contribute to the development of chronic pulmonary disease in AAT deficient individuals. This article will review the importance of AAT as a serine anti-protease, the clinical manifestations of AAT deficiency and specific treatment of the disease. Current therapies including AAT replacement and treatment with synthetic or alternative protease inhibitors are reviewed, along with possible future therapies including those focusing on targeting AAT polymer formation or based on gene therapy.

Cite this article as:

P. Reeves Emer, Cosgrove Sonya, A. Bergin David, M. Greene Catherine and G. McElvaney Noel, New Strategies in Drug Development Focusing on the Anti-Protease- Protease Balance in Alpha-1 Antitrypsin Deficiency, Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 2010; 9 (4) . https://dx.doi.org/10.2174/1871523011009040314