Abstract:
In one embodiment, the invention provides methods of identifying the sensitivity and resistance to therapeutic drug regimens in a subject who suffers from, or who is suspected of suffering from, a Mycobacterium infection, the method comprising administering (1) isotopically labeled Pretomanid and/or Delaminid, or (2) isotopically labeled ethionamide and/or prothionamide, or (3) isotopically labeled pyrazinamide, or (4) isotopically-labeled isoniazid to the subject and thereafter measuring levels in a subject-derived sample of one or more isotopically-labeled markers corresponding to Mycobacterium-actiwated drug metabolites or degradation products, wherein the absence of detectable levels of Mycobacterium-activated drug metabolites or degradation products indicates either that the subject does not suffer from a Mycobacterium infection or suffers from a Mycobacterium infection which is resistant to treatment with the administered drug regimen.
Abstract:
The present invention is directed to the elucidation of the mechanism that human Atg8 protein regulates endolysosomal systems in the cell and the role this protein plays in mediating autophagy. Methods of treating autophagy-mediated disease states with agonists/antagonists of Atg8, STX16 and STX17 proteins are disclosed as are pharmaceutical compositions.