ASGT Press Release

August Issue: Molecular Therapy

This is the press release for the August 1, 2001, issue of Molecular Therapy, the journal of the American Society of Gene Therapy (ASGT). Molecular Therapy is owned and copyrighted by the ASGT, and published monthly by Academic Press.

This information is not embargoed (see embargo policy below). Please cite Molecular Therapy as the source of this information.

All questions should be directed to the Editor (contact information below).

On the cover: Cystic Fibrosis Gene Therapy

Overcoming barriers to CF gene therapy
Despite intense efforts, effective gene therapy for cystic fibrosis remains an elusive goal. However, new and promising strategies are being explored. A review article by Mary Hitt (McMaster University) and David Koehler and Jim Hu (University of Toronto) explores the problems with past approaches and describes promising new treatment modalities. 

["Challenges and Strategies for Cystic Fibrosis Lung Gene Therapy," Mol. Ther. 4: 84-91]

Early intervention for CF treatment
Previous gene therapy approaches to treating CF lungs have failed in the face of thick mucosal lining, inflammatory mediators, the immune response, and the difficulty of getting good vector entry and transduction of the lung epithelial cells. One possible way around these problems is to target the tissue early in development, i.e., in utero. To this end, Boyle et al. (Johns Hopkins University) describe experiments in which they target the fetal pulmonary epithelial cells with an adeno-associated virus (AAV) gene therapy vector by injecting vector into the amniotic fluid. Although the researchers demonstrate safe and successful gene transfer, this method of delivery raises additional questions that need to be addressed before clinical use can be considered.

["In Utero AAV-Mediated Gene Transfer to Rabbit Pulmonary Epithelium," Mol. Ther. 4: 115-121]

Gene therapy for weight loss and maintenance
Although the importance of the hormone leptin in controlling body weight and homeostasis is known, the appropriate clinical use of this molecule is not. It is clear that leptin targets, among other cells, specific neurons within the hypothalamus and elsewhere. Thus, local and persistent production of leptin through leptin gene transfer is a potentially better treatment option than systemic or even local injections of the protein itself.

Previous studies of leptin gene transfer have shown some effect on actual energy expenditure, but little effect on food intake. Is this a question of dosage or proper targeting (or both)? H. Dhillon, S. Kalra, and P. Kalra (University of Florida and Harvard University) look at these issues in a rat model. By testing different dosages of a recombinant AAV vector carrying the leptin gene, injected into the brain ventricles of the animals, they show that a higher dose can both increase energy expenditure and decrease food intake, while a lower dose increases only energy expenditure. Not only does this confirm that multiple pathways are involved in weight control and maintenance, it suggests that delivering leptin in a recombinant AAV vector could be a very efficient clinical method for long-term weight loss and maintenance.

["Dose-dependent effects of central leptin gene therapy on genes that regulate body weight and appetite in the hypothalamus," Mol. Ther. 4: 139-145.]

The conduct of clinical trials
Public trust in gene therapy and gene therapy researchers has been eroded by recent events that were heavily reported over the past two years. However, the promise of gene therapy remains strong, and gene therapy practitioners are taking steps to regain that trust.

The recent increase in oversight and regulation of human clinical trials has been met with efforts by the American Society of Gene Therapy to work with governmental agencies and Society members to assure both patient safety and compliance with existing and new regulations. In this issue, former ASGT president Savio L.C. Woo (Mt. Sinai School of Medicine) describes the recently conducted Clinical Gene Transfer Training Course, jointly sponsored by the ASGT, the NIH, the FDA, and the Mount Sinai School of Medicine. He also argues that this kind of collaborative education is the key to future successful trials of gene therapeutic approaches, and a fundamental part of the mission of the Society.

To that end, the editorial by Inder M. Verma of the Salk Institute and editor-in-chief of Molecular Therapy emphasizes the need for vigilance and openness in reporting adverse events in both clinical and preclinical studies, and cites a recent example.

Also of interest:
mRNA Repair and Restoration of Protein Function
Using Epstein-Barr virus for gene therapy
Non-viral cancer vector
Clinical safety trial of HSV-tk for refractory cancer

EMBARGO POLICY:
Molecular Therapy considers the embargo lifted upon editorial acceptance of a manuscript (i.e., the decision of the editor to accept a manuscript following successful peer review and revision). We make every effort to have manuscripts published electronically before print. Manuscripts still under review should not be reported as being published in Molecular Therapy.

For information contact:
Fintan R. Steele, Ph.D.
Editor, Molecular Therapy
Executive Editor, Genomics
Academic Press
15 E. 26th St. 15th Floor
New York, NY 10010
212-592-1023 phone
646-935-3742 fax
fsteele@acad.com
http://authors.elsevier.com/JournalDetail.html?PubID=622922&Precis=DESC
http://www.academicpress.com/genomics

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