TreatmentUpdate80 - Vol. 8, No. 0; August 1997
Sean Hosein
A series of anti-HIV drugs called antisense compounds (for an explanation of antisense and how it works see the latter part of this article) is under development in North America. Hybridon Inc. has recently halted a trial of one of its antisense products, GEM 91 (gene expression modulation). In reviewing its data the company found that 10 days of iv exposure to the drug caused reduced levels of platelets -- which are needed to help blood clot -- in 3 of 9 volunteers. These 3 people had to temporarily stop taking GEM 91. As well, not all of the 9 subjects had decreased production of HIV. Since some subjects had to stop receiving GEM 91, Hybridon was worried about not being able to continuously suppress production of HIV.
GEM 92
A newer, more stable anti-HIV drug, GEM 92, has been developed by Hybridon. Unlike GEM 91, this drug can be taken orally and the manufacturer plans to conduct studies on people with HIV infection in mid-Autumn 1997 in the United States.
How it's supposed to work
T cells contain genetic material (called DNA) that contains instructions for making proteins that they need to carry out their functions. When HIV infects a T cell the virus inserts its genetic material (or genes) into that of the cells. HIV's genes can then hijack the cell and convert it into a virus factory. Now, researchers at several companies in the USA have developed small molecules called antisense compounds, "usually short pieces of DNA," that work inside HIV-infected cells by homing in on HIV's genes and stopping them from working. In practise, several research teams have found that antisense compounds may have different ways of exerting their antiviral activities and they also appear to trick the immune system into thinking that it is under attack by bacteria, thereby stimulating defense mechanisms.
REFERENCES:
1. 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 1. AIDS Research and Human Retroviruses 1997;13(7):545-554.
2. Anonymous. Hybridon stops development of GEM 91 for AIDS. Press Release. July 25, 1997.
3. Gura T. Antisense has growing pains. Science 1995;270:575-577.
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