Harvard technology may enable the development of designer antibiotics.
Neil Savage
Bacteria that are resistant to most available antibiotics are a growing concern in public health, but one local startup hopes that a novel technology developed at Harvard will enable it to create better versions of germ-killing drugs.
TetraPhase Pharmaceuticals began work last September to develop new forms of tetracycline, a commonly used antibiotic, that can combat antibiotic-resistant bacteria. The company has attracted $25 million in funding and hopes to have at least one drug ready for clinical trials by the middle of 2009.
The company’s technology was developed by Andrew Myers, a professor of chemistry and chemical biology at Harvard who published details of his work in the journal Science in April 2005. Myers has come up with a method to synthesize tetracycline molecules from scratch out of benzoic acid molecules. Drug manufacturers today use bacteria to produce tetracycline and many other types of antibiotics. They then tweak the molecular structure to try to make the drug more effective, in a process called semisynthesis.
“Semisynthesis is extraordinarily limiting, especially in the case of tetracyclines,” Myers says. It’s difficult for a chemist to make significant changes to a molecule—such as swapping one atom for another deep within the molecule’s structure—that’s already been synthesized by bacteria.
Custom made
By contrast, with Myers’s approach, scientists can shape the molecule as they like, creating structures, for instance, that bind more effectively to the bacteria they’re attacking or evade bacterial defense mechanisms. TetraPhase chemists can build tetracycline molecules with a wide range of shapes and configurations, then test the new drugs against antibiotic-resistant strains of bacteria to see which ones work best.
“For the first time, we’ve got a ‘ground-up’ synthesis,” Myers says. “The potential for modification is limited only by our imaginations.” His lab has already come up with nearly 70 tetracycline compounds that show some germ-killing activity.
Chaitan Khosla, a chemistry professor at Stanford, calls Myers’s work “a scientifically amazing accomplishment.” Tetracycline, he adds, is a very complex molecule, and this is the first time someone has figured out how to synthesize it.
TetraPhase is targeting methicillin-resistant Staphylococcus aureus, an aggressive and deadly germ that can fend off most antibiotics and is becoming more prevalent in hospitals.
However, drug resistance is a never-ending battle, as germs continually evolve to defend themselves against the latest drugs. Myers hopes to make versions of tetracycline that can hold off the resistance as long as possible, but the “chemical warfare,” as he calls it, will continue.
Open market
Few new antibiotics have been developed and approved in recent years, so company leaders say the market will welcome their products. The last version of tetracycline came out in 2005—the one before it was approved in 1973—and must be administered intravenously. TetraPhase hopes to come up with one that can be taken orally as well.
Large pharmaceutical companies for the most part have not put much effort into developing antibiotics. That leaves it up to a handful of biotech firms, including ActivBiotics of Lexington, Targanta Therapeutics of Cambridge, and Paratek Pharmaceuticals of Boston, which is also working on tetracyclines.
But only TetraPhase has the technology to build tetracycline antibiotics from scratch, says Lawrence Miller, a co-founder from Mediphase Venture Partners of Newton and chair of the board at TetraPhase.
Even with so many competitors, there’s plenty of room in the market, says Ralph “Chris” Christoffersen, general partner at Morgenthaler Ventures, based in Menlo Park, CA, which invests in Replidyne, another biotech firm focused on antibiotics.
“There could be multiple winners,” says Christoffersen, because each antibiotic treats a different set of diseases.