Grant: CIHR REDI Early Career Transition Award - Pandemic Prepared./Health Emergencies

The cause of tuberculosis (TB) was known before 100 years and since then several drugs and diagnostic tools have been developed. Despite all efforts, until the recent COVID-19 pandemic, TB was the deadliest infectious disease killing every year about 1.6 million people worldwide. The problem still remains as a major public concern. In fact, due to emergence and spread of drug resistant bacteria TB is now even becoming more difficult to treat. In addition to being less effective against drug resistant TB, the main limitation of the existing anti TB drugs is, they have to be given to patients for a very long time. As a result, they cause too much drug related toxicity which leads to poor patient compliance and therefore frequent treatment failures. To reduces this unacceptably high TB related mortality, we need newer drugs that works in a novel way and shorten the treatment duration. One way to achieve this is to develop drugs that boost the host capacity to clear infection. This approach is called host directed therapy (HDT) and the drugs are called host directed drugs. The goal of this research project is to develop new host directed therapy for TB. We proposed to use the commonly prescribed antiallergy drugs that reduce the allergy mediator histamine (antihistamine drugs). My preliminary research findings suggest that they are very effective HDT enabling clearance of Mycobactrium tuberculosis (Mtb), the causative agent for TB, when it resides in an infected human white blood cell. In addition, the proposal also describes a new strategy that will be used to develop novel classes of HDT that are designed to works by facilitating degradation of Mtb by the infected human host cell.