TreatmentUpdate78 - Vol. 7, No. 8; June 1997
Sean Hosein

T cells contain genetic material (called DNA) that carries instructions for making proteins that the cells need to carry out their functions. When HIV infects a T cell, the virus inserts its genetic material (or genes) into that of the cell. HIV's genes can then hijack the cell and convert it into a virus factory. Researchers at several companies in the USA have now developed small molecules called antisense compounds, "usually short pieces of DNA", that work inside HIV-infected cells by homing in on the virus's genes and stopping them from working. In practice, several research teams have found that antisense compounds may actually have different ways of exerting their antiviral activities. They also appear to trick the immune system into thinking that it is under attack by bacteria, thereby stimulating various defense mechanisms.

GEM 91«

One antisense product is GEM 91 (gene expression modulation). In lab experiments, GEM 91 has blocked production of HIV in infected cells longer than AZT and the protease inhibitors. The drug seems safe when given intravenously at an approximate dose of 4 mg/kg of body weight/day for 8 days. GEM 91 has also reduced the amount of HIV inside cells by up to 90%. Among 14 HIV-infected volunteers who received the drug in one study, the greatest drop in virus levels was observed in those with "advanced disease." The manufacturer of GEM 91, Hybridon, plans to recruit 24 subjects with "late-stage AIDS" for further studies in the USA. Test sites will be established at : Mt. Zion Hospital (San Francisco), Columbia Northlake Regional Medical Centre (Tucker, Georgia), San Carlos Hospital (San Juan, Puerto Rico), University of Texas Southwest Medical Centre (Dallas) and Riverside Regional Medical Centre (Hampton, Virgina).

GEM 91 looks promising

Hybridon is also testing a longer-acting antisense molecule called GEM 92 . Yet another compound called GEM 93 is designed to be taken orally. GEM 132, a product for the treatment of CMV-retinitis, is being tested in Europe both intravenously and as direct injections into the eye.

REFERENCES:

1. Anonymous. First success for antisense in HIV. SCRIP 15 April, 1997, page 22.

2. Yamaguchi K, Papp B, Zhang D, et al. The multiple inhibitory mechanisms of GEM 91«, a gag antisense phosphorothioate oligonucleotide, for Human Immunodeficiency Virus Type AIDS Research and Human Retroviruses 1997;13(7):545-554.

3. Zhang R, Yan J, Shahinian H, et al. Pharmacokinetics of an anti-Human Immunodeficiency Virus antisense oligodeoxynucleotide phosphorothioate (GEM 91) in HIV-infected subjects. Clinical Pharmacology and Therapeutics 1995;58:44-53.

4. Gura T. Antisense has growing pains. Science 1995;270:575-577.

970601
CATE7801

Copyright © 1997 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca