MicroProbe Corp. said Tuesday that cell culture results indicate that a newclass of anti-viral agents may lead to treatments for HIV that are moreeffective, less toxic and cheaper than other oligonucleotide drugs. TheBothell, Wash., company has a patent pending on this class of agents aswell as related compounds.
The agents are all phosphodiester oligonucleotides, not phosphothiolates.And they are protein-blocking anti-nucleotides rather than antisensecompounds or nucleotide analogs.
MicroProbe's specific chemistry allows it to use normal backbones and notmodified backbones (backbones are the structural part of the compound onwhich the chemicals are laid). The lead compound of this class of anti-viralagents is called MPC-531, a chain of 32 of the same nucleotide units witha normal phosphodiester backbone. It inhibits reverse transcriptase andDNA polymerase.
Although the drug's precise mechanism is unknown, Harvey Hoyt, MicroProbe'schief executive officer, said it may be less toxic because the chemicalbackbone of the oligonucleotide does not have to be modified. "We arespeculating that when you have to modify a backbone to modify a chemicalin a product, it has some degree of toxicity," he said.
"We believe this discovery is important for three reasons," said Hoyt ofthe class of agents. "First, it has very low toxicity in the cell culturecompared to its effectiveness. Secondly, it showed a broad spectrum ofactivity in the systems that we have utilized as a class of compounds.Finally, it has the potential for lack of cross-resistance down the road."The company believes that MPC-531 may also be effective againstEpstein-Barr virus.
MicroProbe has begun animal trials on the new drug and hopes to enterhuman clinical trials by mid-1995.
Hoyt added that MPC-531 would be less expensive to manufacture than otheroligonucleotides because the length of the DNA chain and the non-modifiedbackbone of the drug will make it cheaper to produce than other drugs inits class.
MicroProbe's stock (NASDAQ:MPRO) jumped 66 percent ($2.63) on the news,closing at $6.63 a share.031694MicroProbe
-- Philippa Maister
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