Gene therapy (alpha1-antitrypsin) (GeneMedicine/Vanderbilt).

Abstract

GeneMedicine is participating in a physician-initiated phase I clinical trial with its non-viral gene therapy for the treatment of alpha1-antitrypsin (AAT) deficiency, in collabo-ration with Vanderbilt University Medical Center [220256]. AAT inhibits elastase and could be useful in the treatment of emphysema [169628]. The product is designed to be administered by inhalation and to provide prolonged local production of AAT in the lung. Positive phase I trial results were presented at the American Lung Association and American Thoracic Society conference in May 1998. The therapy was shown to be safe, with AAT protein levels in nasal lavage fluid increased in all five patients. An anti-inflammatory effect was also observed which was not achieved by administration of the AAT protein alone [287048]. GeneMedicine's approach to gene therapy is the delivery of gene-containing plasmids to target cells in the body. Rather than using a virus to deliver the genetic material into the target cells, the plasmids are condensed into small particles using the DOTMA cationic lipid (licensed from Roche Bioscience), and administered by inhalation or injection. These formulations alter the net negative charge of nucleic acid to a positive charge, allowing the plasmid to interact with the negative cell membrane, and so pass into the cytoplasm with subsequent localization into the nucleus. Once the gene is in the target cell, the construct is designed to control the production, duration and level of the therapeutic protein. The company anticipates that its gene expression system will remain separate from the body's chromosomal DNA and will degrade naturally, permitting repeat administration of the gene therapy [221069,220256]. The lung gene therapy platform may be applicable to other lung diseases such as cystic fibrosis, chronic obstructive pulmonary disease, and pulmonary infections.

• Authors: R Krishnan
• Journal: IDrugs : the investigational drugs journal (IDrugs) Vol. 1 Issue 4 Pg. 486-9 (Aug 1998) ISSN: 1369-7056 [Print] England
• PMID: 18465583 (Publication Type: Journal Article)