 |
Sept. 24, 2003 – They might be nano’s artificial molecule, but dendrimers are taking real steps toward fighting HIV and sexually transmitted diseases in women.
 |
Starpharma Pooled Development Ltd. of Melbourne, Australia, gained approval in July from the U.S. Food and Drug Administration to start human trials of VivaGel, a dendrimer-based topical gel designed to prevent or reduce disease transmission during sexual intercourse. It’s the first dendrimer — and defined nanostructure — cleared for clinical testing, according to John Raff, Starpharma’s chief executive.
 |
Raff said Starpharma chose the application first because it takes advantage of the synthetic molecule with branching parts — precise, nanoscale scaffolding upon which the right chemical compounds can be attached. Such tailored dendrimers can interact with viruses at multiple sites — a concept called polyvalence — in a manner that mimics proteins and other natural processes. Polyvalent pharmaceuticals are viewed by some drug researchers as more effective than conventional small molecule drugs.
VivaGel also succeeded in preventing infection in monkey trials using a humanized strain of simian immunodeficiency virus. Studies conducted at University of Washington found that a single vaginal application of the gel protected 100 percent of the macaques exposed to the virus. The gel not only prevents adhesion to healthy cells, but also incapacitates the virus even if it gets into the cell.
“Strains of viruses resistant to other drugs were not resistant to this polyvalent dendrimer approach,” Raff said. “It’s active against HIV, chlamydia and herpes. … It’s blocking their entry.”
Raff expects the first phase of clinical trials — human safety studies — to start by late October in Australia. He said the company can’t afford to go it alone, and seeks funding from big pharmaceutical firms and major research institutions. He’s optimistic that some eyes have opened to the possibilities of polyvalent drugs, after one of the year’s biggest pharma deals signed in January between pharma giant GlaxoSmithKline PLC (GSK) and privately held Theravance Inc.
London-based GSK agreed to pay up to nearly $500 million for rights to San Francisco-based Theravance for its cross-linked polymers in long-acting asthma treatment. Although they aren’t dendrimers, Raff said the deal shows the promise of polyvalence in the market. “It really made the world sit up and say, ‘Crikey, there must be something with this polyvalence area.'”
Donald Tomalia, the Michigan-based inventor of dendrimers, now serves as president and chief technology officer of Dendritic Nanotechnologies Ltd., where Starpharma is the largest shareholder. While Raff calls Tomalia the “inventor, pioneer and champion” of dendrimers, Tomalia said Starpharma deserves the credit for building on his
foundation.
“It’s pretty exciting to us on this end — it really does take this to the next step,” Tomalia said. “It’s more than a container or (device) delivering the drugs. We can now see this is what’s really allowing dendrimers to be nanopharmaceuticals in their own right.”
It’s one of a few recent gratifying moments for Tomalia, who has seen the value of dendrimers since discovering how to make them in 1979 but has yet to find a major commercial breakthrough.
The Institute for Soldier Nanotechnologies in May named Dendritic Nanotechnologies an industrial partner. The center, funded by the U.S. Army and based at the Massachusetts Institute of Technology, is developing new equipment for soldier protection and survivability. The same month, The Society of Polymer Science in Japan honored him for outstanding achievement in the field.
“It’s a nice feeling in our whole group — the world has finally heard our story,” he said. “Some real beneficial things are happening. … It’s just the beginning of something that I think is very positive for the human condition.”