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Biological Chemistry
Better Drugs for Tuberculosis
Drug discovery partnership aims to speed search for improved treatments
by VIVIEN MARX
March 28, 2005
| A version of this story appeared in
Volume 83, Issue 13
DRUG DEVELOPMENT
Coinciding with world TB Day on March 24, the nonprofit Global Alliance for TB Drug Development and GlaxoSmithKline (GSK) have announced an agreement to develop new treatments for tuberculosis.
According to the TB Alliance, no new TB drugs have been introduced in decades. The current regimen involves taking several drugs for six to nine months. Toxic side effects are frequent, as are multi-drug-resistant TB strains. AIDS patients who are infected with TB often cannot take the TB drugs.
TB Alliance President Maria C. Freire says that, given the 2 million TB deaths annually, the project with GSK "gives us reason for optimism." The alliance also has a partnership with the Novartis Institute for Tropical Diseases.
David Pompliano, GSK's head of biology, says the project builds on efforts already under way at his company's Tres Cantos, Spain, facility, which is dedicated to diseases of the developing world. The project is also, as Pompliano says, "plugged into the drug discovery machine" at GSK to include high-throughput screening, bioinformatics, and target validation work.
Fifty full-time scientists in Spain, 25 of whom will be new hires, are to devote their attention to TB drugs.
A drug lead currently undergoing optimization is in a novel class of antibiotics called pleuromutilins. "The goal is to have chemists modify the core pleuromutilin structure to optimize the antibacterial activity against TB," Pompliano says. "We have already made 500 analogs in this class."
GSK will also apply its compound library to the partnership. "What we are doing is going back to those compounds for which we know the molecular target and looking for anti-TB activity," Pompliano says. Another part of the program, now in the lead identification stage, targets two enzymes specific to Mycobacterium tuberculosis.
The agreement stipulates that any resulting medicines will be "affordable and accessible to those most in need."
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