Starpharma gel wards off retrovirus infection

Melbourne nano-biotech company Starpharma Pooled Development (ASX:SPL) announced today that tests in the US have shown that its lead compound, a intravaginal gel developed to protect against sexually transmitted diseases, is completely effective in warding off an HIV-like retrovirus infection in macaque monkeys.

Dr Che-Chung Tsai’s research group of the University of Washington, in Seattle, tests in the US, a single application the water-based gel, containing a five per cent solution of Starpharma’s giant dendrimer molecule SPL7103, prevented infection by a humanised variant of simian immunodeficiency virus (hSIV).

In a control group, 75 per cent of female macaques treated with a placebo gel became infected.

Studies of the Starpharma compound are being funded by the Division of AIDS (DAIDS), the National Institute of Allergy and Infectious Diseases (NIAID), the U.S. National Institutes of Health (NIH), and the U.S. Department of Human and HealthServices (DHHS) – Raff said the NIH has been a strong supporter if its anti-STD candidate therapy.

Full details of the current study are being presented today at the Topical Microbicides Development and Evaluation Workshop in Washington DC in the US.

Many researchers seeking ways to prevent AIDS infection, like Professor Roger Short, of the Royal Women’s Hospital in Melbourne, now believe controlling STDs is integral to controlling the HIV-AIDS epidemic.

Short says vaginal lesions caused by other sexually transmtted microbes create entry points for the AIDS virus – a multi-valent microbicide would reduce the risk of HIV infection by preventing such damage.

Starpharma’s anti-STD dendrimer-based gel has been designed to be used before intercourse. According to Starpharma CEO, John Raff, it has also been shown to protect against genital herpes – another viral infection - and the Chlamydia bacterium.

SPL7013 had previously displayed promising activity against various strains of HIV in cell-based assays. The latest tests in female macaques, although they involve hSIV, a retrovirus closely related to HIV, confirm that promise.

Dendrimers are a novel class of huge, synthetic molecules with highly regular, elaborately branched structures, formed by building up layers of repeating sub-units around a central core.

In the case of SPL7103, the main building block is the amino acid lysine, with sulfonate groups coating the outermost surface.

Dendrimers are actually nanomolecuar devices, enormously larger than conventional synthetic drug molecules. Starpharma CEO Dr John Raff says SPL103 comprises about 16,000 atoms – comparable to a small protein.

The Starpharma compound seals off the cell-surface receptor to which the human herpes virus, and the Chlamydia bacterium, both attach.

With HIV, the giant molecule locks onto the GP120 protein on the virus’s surface, which normally fuses with the CD4 receptor on the surface of lymphocytes, allowing the virus to enter and replicate.

In the latest trial, none of the female macaques in the experimental group showed any adverse symptoms.

Raff says when the anti-viral gel was tested in female rabbits last year, some toxic effects on the vaginal lining were observed. Starpharma delayed applying to the Food and Drug Administration for Investigational New Drug status for the new compound

There was no sign of toxicity in earlier trials on female rats and mice, and none when female rabbits were directly injected with SPL7103.

Raff says the vagina lining in rabbits appears unusually sensitive to damage, perhaps because female rabbits ovulate only after intercourse.

Several other companies testing anti-STD therapies in female rabbits have experienced similar problems, calling into question the suitability of rabbits as a model for testing vaginal microbicides designed for human use.

At the end of 2002, 42 million people were living with AIDS, of whom 19.2 million were women (www.unaids.org)