Translating the Clinical Development of the First Small Molecule Probe of TB

PI: Ben Davis

Department: Chemistry

Mycobacterium tuberculosis (Mtb) is the bacterium which causes tuberculosis (TB). Millions of human deaths are caused by TB infection (not only in developing countries). Current approaches to diagnose TB lack specificity and are time consuming. More specific and efficient imaging methods are urgently needed for early diagnosis.

Trehalose (Tre), a non-mammalian sugar, is a precursor of cell-wall components in Mtb. It exists as lipid-conjugates (trehalose mycolates) in the outer cell wall of Mtb. In collaboration with the National Institute of Health (NIH) of the USA, Prof Davis’ group has used their understanding of the biology of TB to create derivatives of Tre that, in pre-clinical studies, are taken up selectively into the Mtb.

We have designed, created and tested successfully these for use in positron emission tomography (PET-CT), thereby allowing direct, non-invasive imaging of TB disease with unprecedented sensitivity.

Now, to enable US Food and Drug Administration (FDA) approval, the group needs to produce multigram quantities using designed enzymatic synthesis for safety and efficacy studies at the NIH. Once these studies are completed, we will go on to test TB imaging in humans with Pre-Investigational New Drug (pre-IND) approval in a variety of ‘front line’ countries where the disease is causing a serious threat and where PET-CT methodology is widely available (South Africa, South Korea, China).