Gene therapy approaches for inherited and acquired lung diseases

Our plain-English summary of Gene therapy approaches for inherited and acquired lung diseases, by D.T. Curiel, J.M. Pilewski, S.M. Albelda (American Journal of Respiratory Cell and Molecular Biology, 1996).

The study

• Authors: D.T. Curiel, J.M. Pilewski, S.M. Albelda
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 1996;14(1):1-18
• Type of article: Review
• Cited by: 83 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Gene therapy is the treatment of any disorder or pathophysiologic state based upon the transfer of genetic information. The lung represents a major target of gene therapy for the treatment of genetic disorders such as cystic fibrosis and alpha 1-antitrypsin deficiency. Other diseases are also being targeted, including pulmonary inflammation, surfactant deficiency, pulmonary hypertension, lung cancer, and malignant mesothelioma. This review will examine some general concepts regarding gene transfer and gene therapy, provide an overview of the current vectors being developed to achieve safe and efficient gene transfer, and summarize the ongoing work to apply this new technology to the treatment of both inherited and acquired pulmonary diseases. Although tremendous progress has been made in the ability to successfully transfer genes to cells, there are several unresolved problems limiting the clinical application of this technology to human pulmonary disease. However, as vector technology evolves, gene therapy may become a reality for a number of lung diseases.

In plain English

This article was a review (a "minireview") of gene therapy, meaning treatment based on transferring genetic material into cells, for lung diseases. It reported no new research of its own and did not discuss asbestos or asbestos exposure. The authors described the carriers used to deliver genes, including several types of virus and non-viral carriers such as liposomes. They summarized published work on cystic fibrosis, alpha1-antitrypsin deficiency, lung inflammation, surfactant deficiency, pulmonary vascular disease, lung cancer and malignant mesothelioma, for which they wrote there was no effective therapy. In reviewed animal studies, an adenovirus carrying a herpes virus gene (Ad.RSVtk), followed by the drug ganciclovir, eradicated visible tumor in 90% of immunodeficient (SCID) mice with human mesothelioma tumors in the peritoneal cavity. Similar results were reported in rats with mesothelioma in the pleural space. A Phase 1 safety trial in mesothelioma patients had been approved. The authors reported that early human cystic fibrosis trials showed limited efficacy and worrisome toxicity. They concluded that unresolved problems limited clinical use, but that gene therapy may become a reality as vector technology evolves.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review (minireview) of published research on gene therapy for lung diseases
• Who was studied: No study subjects of its own; the review covered published laboratory, animal and early human studies of gene therapy for inherited lung diseases (cystic fibrosis, alpha1-antitrypsin deficiency) and acquired lung diseases (including lung cancer and malignant mesothelioma)
• Main results:
  • The authors stated that there was no effective therapy for malignant mesothelioma
  • In reviewed studies, Ad.RSVtk was used to treat established human mesothelioma tumors growing in the peritoneal cavities of immunodeficient SCID mice (printed "scm" in the scanned text). After ganciclovir therapy, macroscopic tumor was eradicated in 90% of animals and microscopic tumor was undetectable in 80%.
  • The review reported similar results in a rat model of mesothelioma growing in the pleural space
  • A Phase 1 clinical trial to assess the safety of Ad.RSVtk in patients with mesothelioma had recently been approved by the Recombinant DNA Advisory Committee
  • According to the review, the few reported human trials of cystic fibrosis gene transfer showed limited efficacy and worrisome toxicity
  • For thoracic cancers including mesothelioma, the authors identified incomplete understanding of molecular causes and limited gene delivery as major challenges. Current vectors could not transduce all or most tumor cells.
• The authors' conclusion: The authors concluded that, despite progress in transferring genes to cells, several unresolved problems limited clinical application to human lung disease, but that gene therapy may become a reality for a number of lung diseases as vector technology evolves

Topics

Medical terms in this study, explained in our Lexicon: Fibrosis, Inflammation, Pulmonary Hypertension, Lung Cancer, Malignant Mesothelioma.

Related studies

• Gene therapy for lung diseases: development in the vector biology and novel concepts for gene therapy applications — M. Suzuki, T. Matsuse, et al. (2001)
• Gene therapy for mesothelioma and lung cancer — A. Vachani, E. Moon, et al. (2010)
• Differential sensitivity of thoracic malignant tumors to adenovirus-mediated drug sensitization gene therapy — W.R. Smythe, H.C. Hwang, et al. (1995)
• Gene therapy for mesothelioma — A. Vachani, E. Moon, et al. (2011)
• Mesothelioma: an inviting but challenging target for gene therapy — R.G. Crystal (2010)
• Cytokine gene therapy or infusion as treatment for solid human cancer — B.W. Robinson, S.A. Mukherjee, et al. (1998)

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