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Tuberculosis Drug Discovery Project
Tuberculosis is a public health problem of staggering proportions. The disease infects one in three people on the planet and kills two million people each year after attacking them in their most productive time of life. Although the greatest burden falls on the developing world, the link between TB and the HIV/AIDS epidemic-immigration from countries where TB is widespread-and the recent surge of multi-drug-resistant cases make tuberculosis a top public health priority in the developed world as well.
Although TB can be treated, current treatment regimens extend over six to nine months—a lengthy process that, combined with drug side effects, often meets with poor compliance. Poor compliance, in turn, contributes to drug-resistant forms of the disease. A vaccine provides some protection against TB disease in young children, but people who have been immunized can still carry the silent infection—as do one-third of the world's population—and go on to develop disease later in life.
In 2006, The Paul G. Allen Foundation awarded the Seattle Biomedical Research Institute (SBRI), an emerging leader in discovery science, a five-year grant to create a Center of Excellence for discovering new approaches to treating TB. The Institute's goal—to eradicate the disease—has as its first step increasing the success of treatment by reducing the drug regimen to no more than two weeks. A shorter course of treatment will undoubtedly meet with greater compliance and head off the frequent reinfection that occurs when treatment has not been complete. SBRI is seeking a way to kill not only the active TB bacteria but also the dormant, or sleeping, TB bacteria that coexists with the active form in a person's body. It is this latent bacteria, which may lie dormant for up to six months, which often flares into disease later on, long after the patient has stopped taken their medications and exhibits no external signs of disease.
Recent advances in research and technology make the SBRI grant extremely promising. The researchers will make use of existing genome sequences for the disease, which identify the potential targets for drug therapy. They will also examine the expression of genes and proteins and their effects on cell metabolism in both the active and latent forms of the disease.
SBRI brings depth of experience to the TB project, built through several years' research on malaria which led to the discovery of the malaria antigen. The Institute has used Foundation funding to assemble a world-class TB research team and establish the technologies and facilities where ambitious investigators can flourish.
Funding from the Foundation is supporting initial scientific studies, leveraging support from others, including the National Institutes of Health, and laying the groundwork for an expanded, self-sustaining program of research. One day, it is hoped, that research will translate into the development of drugs that will succeed in eradicating tuberculosis.
"Understanding the dynamics of TB replication and death during infection is critical to our efforts to develop more effective therapies. This field is rife with untested hypotheses based on imprecise and indirect experiments... The Lab has developed a novel tool to measure TB replication and death in vivo, and is using this tool to challenge prevailing assumptions."
— SBRI March, 2009
Web site: www.sbri.org
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