PMID- 30723782
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2372-952X (Print)
IS  - 2372-952X (Electronic)
IS  - 2372-952X (Linking)
VI  - 5
IP  - 4
DP  - 2018 Aug 17
TI  - Intrapleural Gene Therapy for Alpha-1 Antitrypsin Deficiency-Related Lung 
      Disease.
PG  - 244-257
LID - 10.15326/jcopdf.5.4.2017.0160 [doi]
AB  - 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.
FAU - Stiles, Katie M
AU  - Stiles KM
AD  - Department of Genetic Medicine, Weill Cornell Medical College, New York, New 
      York.
AD  - KMS and DS contributed equally to this review.
FAU - Sondhi, Dolan
AU  - Sondhi D
AD  - Department of Genetic Medicine, Weill Cornell Medical College, New York, New 
      York.
AD  - KMS and DS contributed equally to this review.
FAU - Kaminsky, Stephen M
AU  - Kaminsky SM
AD  - Department of Genetic Medicine, Weill Cornell Medical College, New York, New 
      York.
FAU - De, Bishnu P
AU  - De BP
AD  - Department of Genetic Medicine, Weill Cornell Medical College, New York, New 
      York.
FAU - Rosenberg, Jonathan B
AU  - Rosenberg JB
AD  - Department of Genetic Medicine, Weill Cornell Medical College, New York, New 
      York.
FAU - Crystal, Ronald G
AU  - Crystal RG
AD  - Department of Genetic Medicine, Weill Cornell Medical College, New York, New 
      York.
LA  - eng
PT  - Journal Article
DEP - 20180817
PL  - United States
TA  - Chronic Obstr Pulm Dis
JT  - Chronic obstructive pulmonary diseases (Miami, Fla.)
JID - 101635411
PMC - PMC6361473
OTO - NOTNLM
OT  - alpha-1 antitrypsin deficiency
OT  - gene therapy
COIS- Adverum Biotechnologies has licensed the AAVrh.10hAAT intrapleural technology and 
      investigational new drug from Cornell University. RGC is a consultant and holds 
      equity in Adverum. RGC, DS, SK share licensing fees paid to Cornell University.
EDAT- 2019/02/07 06:00
MHDA- 2019/02/07 06:01
PMCR- 2018/08/17
CRDT- 2019/02/07 06:00
PHST- 2019/02/07 06:00 [entrez]
PHST- 2019/02/07 06:00 [pubmed]
PHST- 2019/02/07 06:01 [medline]
PHST- 2018/08/17 00:00 [pmc-release]
AID - 10.15326/jcopdf.5.4.2017.0160 [doi]
PST - epublish
SO  - Chronic Obstr Pulm Dis. 2018 Aug 17;5(4):244-257. doi: 
      10.15326/jcopdf.5.4.2017.0160.