Intrapleural Gene Therapy for Alpha-1 Antitrypsin Deficiency-Related Lung Disease.

Publication Type Academic Article
Authors Stiles K, Sondhi D, Kaminsky S, De B, Rosenberg J, Crystal R
Journal Chronic Obstr Pulm Dis
Volume 5
Issue 4
Pagination 244-257
Date Published 08/17/2018
ISSN 2372-952X
Abstract Alpha-1 antitrypsin deficiency (AATD) manifests primarily as early-onset emphysema caused by the destruction of the lung by neutrophil elastase due to low amounts of the serine protease inhibitor alpha-1 antitrypsin (AAT). The current therapy involves weekly intravenous infusions of AAT-derived from pooled human plasma that is efficacious, yet costly. Gene therapy applications designed to provide constant levels of the AAT protein are currently under development. The challenge is for gene therapy to provide sufficient amounts of AAT to normalize the inhibitor level and anti-neutrophil elastase capacity in the lung. One strategy involves administration of an adeno-associated virus (AAV) gene therapy vector to the pleural space providing both local and systemic production of AAT to reach consistent therapeutic levels. This review focuses on the strategy, advantages, challenges, and updates for intrapleural administration of gene therapy vectors for the treatment of AATD.
DOI 10.15326/jcopdf.5.4.2017.0160
PubMed ID 30723782
PubMed Central ID PMC6361473
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