Grant: Proof of Principle Program - Phase I

Tuberculosis (TB), remains a large public health problem worldwide. Incidence and severity of TB infections have increased dramatically in recent years threatening mankind and posing a major global health challenge. TB kills more adults per year than any other single pathogen worldwide. There were more cases of TB in 2008 than in any point in history, and currently 2 to 3 million people die globally from TB every year. The worldwide HIV/AIDS pandemic is fuelling this increase in TB infections. TB is the most common opportunistic infection and a leading cause of death among people with HIV. In addition, other immunocompromised individuals such as cancer patients, patients with organ transplants, and elderly people, are highly susceptible to TB infection as well as reactivation of latent TB. Recent outbreaks of multi-drug-resistant (MDR) TB globally and even in North America and Europe has killed over 80% of those contracting the disease. In addition, extremely drug resistant TB (XDR-TB) and totally drug resistant (TDR-TB) have emerged with 100% mortality as an even more ominous threat worldwide. It is frightening that TB is highly contagious and is easily spread through the air like the common cold. The growing number of cases of MDR, XDR and TDR-TB worldwide and treatment failure is of utmost concern. This has turned TB into one of the world's most pressing health problems. Consequently, there is a tremendous need to develop new therapeutic approaches to control this deadly disease. In our studies, we have identified non-toxic agents that are potent and selective inhibitors of various wild-type and drug-resistant strains of mycobacteria. The overall goals of this research are to investigate these promising agents in preclinical animal studies to advance our technology and develop a new generation of drugs for tuberculosis infections. These studies will provide a major impact on the health of Canadians and people worldwide.