ASGCT Press Release
For Immediate Release
July 17, 2002 |
Contact: Fintan R. Steele, Ph.D.
Fax: 646-935-3742 |
This is the press release for the July 2002 issue of Molecular Therapy, the journal of the American Society of Gene Therapy. Academic Press, an imprint of Elsevier Science, publishes Molecular Therapy monthly for the Society.
Please credit Molecular Therapy as the source of this information.
The embargo is lifted upon your receipt of this message. Embargo of manuscripts at Molecular Therapy applies only to articles that have not completed the review process, i.e., only articles accepted for publication may be cited as being in Molecular Therapy. All questions should be directed to the editor (see below for contact information).
The results of two phase II clinical trials are presented in this issue of Molecular Therapy, as well as an analysis of the state of germ line transmission of a gene therapy vector in another ongoing trial.
The majority of cystic fibrosis patients have one or more mutations in the gene that encodes a critical membrane protein (CFTR), which functions as a chloride channel. These mutations result in the abnormal CFTR protein not making it to the cell surface, causing the variety of abnormalities that contribute to cystic fibrosis. Attempts to genetically replace or repair the mutant gene have fallen short to date. But there are other interventions that may work, including targeting the process by which the abnormal protein is degraded before it gets a chance to reach the membrane.
Pamela Zeitlin of the Johns Hopkins University School of Medicine in Baltimore and her colleagues describe a phase I/II trial of Buphenyl, a short chain fatty acid, that restores the "maturation" of the mutant CFTR protein. The researchers did not know if the mutant protein would function "normally" once it made it to the membrane surface, although they hoped that
it would based on earlier animal studies. As it turns out, the Buphenyl treatment (which was safe and well-tolerated) resulted in a significant induction of chloride transport, suggesting not only that the mutant protein can function if given a chance to get to the right place, but also that Buphenyl may be a viable therapeutic option for treating cystic fibrosis.
Zeitlin, P.L., et al. (2002). Evidence of CFTR Function in Cystic Fibrosis after Systemic Administration of 4-Phenylbutyrate." Mol. Ther. 6: 119-126.
Although there have been successes reported in gene therapy trials of vascular endothelial growth factor (VEGF), particularly in cardiac applications, there has been no rigorous proof that this approach works in human beings (that is, a random, double-blinded trial). Now, in a carefully controlled and elegantly designed phase II trial of VEGF gene therapy for lower limb ischemia, it is safe to say that this approach holds great clinical promise.
Seppo Yla-Herttuala and his colleagues at the Kuopio University Hospital in Finland compared two different gene therapy vectors (adenovirus and a nonviral vector) to a placebo in the lower limbs of patients with chronic lower-limb ischemia. Subsequent angiography revealed improvement (increased vascularity) in both gene therapy groups, although the adenovirus-treated group showed an increase in anti-adenovirus antibodies. However, the results are encouraging for further clinical studies of both vectors.
Makinen, K., et al. (2002). Increased Vascularity Detected by Digital Subtraction Angiography after VEGF Gene Transfer to Human Lower Limb Artery: A Randomized, Placebo-Controlled Double-Blinded Phase II Study. Mol. Ther. 6: 127-133
Recent news from the ongoing hemophilia gene therapy trial has appeared in some places as "germ line transmission of gene therapy." Not quite. But the issue has "reared its ugly head," writes Trisha Gura, who considers not only the science but also the regulatory response in her interesting outline of this thorny issue facing the gene therapy community.
(Note to science writers: We are soliciting both writers and ideas for this section. If interested, contact the editor).
The use of gene therapy is not limited to treating genetic diseases. Indeed, gene therapy vectors can be used to delivery a variety of therapeutic genes that can repair broken bones or ward off injury in the first place. In one of the most interesting examples of this use, Robert Frisina of the University of Rochester School of Medicine and Dentistry and his colleagues
use a gene therapy approach to ameliorate one of the most feared side-effects of cancer chemotherapy: loss of hearing.
Cisplatin, a commonly used chemotherapeutic agent, can destroy the critical hair cells and the spiral ganglion neurons, resulting in partial or even complete deafness. The Rochester group tested whether pretreatment of the cochlea with a gene therapy vector carrying the gene encoding neurotrophin-3 (a neuroprotective protein) could save the delicate hearing cells in aged mice given cisplatin after the gene therapy. Compared to controls not pretreated with NT-3, the NT-3 pretreated mice maintained a significant number of hair cells and spinal ganglion neurons. Not only is this a promising preventative for chemotherapy-induced hearing loss, but may also be useful in preventing the hearing degeneration associated with normal aging.
Bowers, W. J., et al. (2002). Neurotrophin-3 Transduction Attenuates Cisplatin Spiral Ganglion Neuron Ototoxicity in the Cochlea. Mol. Ther. 6: 12-18.
An "Artificial Virus" to Cross the Blood-Brain Barrier in Treating Brain Cancers.
Increasing the Carrying Capacity of AAV as a Gene Therapy Vector.
A Regulatable Antitumor Gene.
Tracking Hematopoietic Stem Cells in Living Nonhuman Primates.
Fintan R. Steele, Ph.D.
Molecular Therapy/Genomics
Academic Press/Elsevier Science
15 E. 26th St. 15th Floor
New York, NY 10010
f.steele@elsevier.com
The American Society of Gene & Cell Therapy (ASGCT) is a professional non-profit medical and scientific organization dedicated to the understanding, development and application of genetic and cellular therapies and the promotion of professional and public education in the field. For more information on ASGCT, visit its website, www.asgct.org.
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