Author Affiliations

1. UCL Respiratory, Division of Medicine, University College London, United Kingdom

Address correspondence to:

David Lomas, MD, PhD
UCL Respiratory, Division of Medicine
Rayne Building
University College London
WC1E 6BN
London, UK
Email: d.lomas@ucl.ac.uk

Abstract

Alpha-1antitrypsin deficiency (AATD) results from the intracellular polymerization and retention of mutant alpha-1antitrypsin (AAT) within the endoplasmic reticulum of hepatocytes. This causes cirrhosis whilst the deficiency of circulating AAT predisposes to early onset emphysema. This is an exciting time for researchers in the field with the development of novel therapies based on understanding the pathobiology of disease. I review here augmentation therapy to prevent the progression of lung disease and a range of approaches to treat the liver disease associated with the accumulation of mutant AAT: modifying proteostasis networks that are activated by Z AAT polymers, stimulating autophagy, small interfering RNA and small molecules to block intracellular polymerization, and stem cell technology to correct the genetic defect that underlies AATD.

Citation

Citation: Lomas DA. New therapeutic targets for alpha-1 antitrypsin deficiency. Chronic Obstr Pulm Dis. 2018; 5(4):In press. doi: http://dx.doi.org/10.15326/jcopdf.5.4.2017.0165

Keywords

emphysema, alpha-1 antitrypsin deficiency, cirrhosis, conformational disease, small molecules, siRNA, proteostasis, autophagy

Full Text

Click to read New Therapeutic Targets for Alpha-1 Antitrypsin Deficiency

PDF Download

PDF Version (537KB)