ASGCT Press Release

This is the press release for the November, 2001, issue of Molecular Therapy, the journal of the American Society of Gene Therapy. Molecular Therapy is published monthly by Academic Press, an imprint of Elsevier Science.

Please credit Molecular Therapy as the source of this information.

The embargo is lifted upon your receipt of this message. PDF files of these manuscripts (with author contact information) are available to direct recipients of this message on request. All questions should be directed to the editor (see below).

On the cover:
Filling the brain
("Towards Global and Long-Term Neurological Gene Therapy: Unexpected Transgene-Dependent, High-Level, and Widespread Distribution of HSV-1 Thymidine Kinase throughout the CNS." A. J. Zermansky, et al. (2001). Molecular Therapy 4: 490-498.)

The most difficult hurdles facing gene therapy for wide-spread central nervous system disorders is disseminating the vector and its transgene throughout the brain and getting long-term expression of the transgene product. Why these are such intractable problems remains a mystery. Nevertheless, a paper in this month's issue of Molecular Therapy reports the surprising finding that distribution and long-term expression may be dependent on the transgene itself regardless of the vector used.

Using a recombinant adenovirus vector (a commonly used gene therapy vector), Pedro Lowenstein of the Gene Therapeutics Research Center in Los Angeles and his colleagues demonstrate that different transgenes delivered using the same type of vector show different spread and longevity. They transferred recombinant adenovirus containing the gene encoding herpes simplex virus type 1 thymidine kinase (HSV-TK) or the gene encoding beta-galactosidase into rodent brains and tracked both the distribution and the length of gene expression. Where beta-galactosidase expression was very limited in both space and time, HSV-TK expression persisted for up to twelve months across a wide area of the brain.

This surprising finding renews hope for effective neurological gene therapy and calls for a re-examination of previous studies where it was believed that disappointing results were a result of the vector used.

More than meets the eye
("Long-term Protection of Retinal Structure but Not Function Using RAAV.CNTF in Animal Models of Retinitis Pigmentosa." F.-Q. Liang, et al.(2001). Molecular Therapy 4: 461-472.)

Gene therapy of inherited blindness has gathered a lot of attention over the past few years. Several different research groups have published results showing that the transfer of a variety of neural protection genes (neurotrophic factors) can slow or prevent the disintegration of the retina. However, these initial positive findings may not be all they appear to be. In this issue of Molecular Therapy, Jean Bennet of the University of Pennsylvania report work that suggests that preserving retinal cells does not equate with preserving retinal function.

Ciliary neurotrophic factor (CNTF) is considered one of the most promising of these proteins for treating retinal degeneration. Bennet et al. injected a recombinant adeno-associated virus (AAV) vector containing the gene that encodes CNTF into one eye of rats with an inherited form of retinitis pigmentosa. The other eye served as a control. Although the physical degeneration of retinal cells in the CNTF-injected eye was dramatically slowed, subsequent functional tests (in this case an electroretinogram, a measurement of electrical activity in the retina) revealed that function did not follow form.

This work has implications not only for interpreting previously published results using CNTF and other neurotrophic factors to treat blindness, but emphasizes the importance of understanding the basic mechanisms behind how these neurotrophic factors work prior to moving to human trials.

The History of Gene Therapy: The Cline Affair
(E. Beutler. (2001). Molecular Therapy 4: 396-397.)
Despite the common belief that clinical gene therapy is a recent phenomenon, the fact is that several earlier forays into the clinic were conducted (and roundly condemned). Last month the first series installment focused on the work of Stanfield Rogers in Germany. This month, Ernest Beutler of the Scripps Institute reflects on the 1980 trial conducted by Martin Cline of UCLA. According to Beutler, the outcry that followed Cline's study of beta-thalessemia patients in Italy had the positive effect of focusing and emphasizing the regulatory rules put in place to protect human subjects in the US and, as the patients were not harmed, may have helped abate the then-rampant fear about DNA transfer into humans. Beutler concludes that "the episode is a tragic one, because it interrupted the efforts of a highly talented, productive scientist who was in too much of a hurry to see patients benefit from the marvels of modern molecular biology.

Gene Therapy and Jurisprudence (editorial)
(I. Verma. (2001). Molecular Therapy 4: 393.)
Gene therapy, like any other biomedical advance, does not occur in a social or ethical vacuum. In the US in particular, the nature of legal deliberation means that the law is less and less adequate to address novel issues raised by rapidly changing biotechnology. Inder Verma reflects on a recent gathering of jurists who are trying to come to grips with the invasion of their courtroom by 21st century science. He argues that engaging in dialogue now will prevent future problems.

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

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.

# # #