Rapid, simultaneous detection of multiple N-acetyltransferase gene polymorphisms and prediction of isoniazid metabolism to optimize treatment of tuberculosis

In nearly all current medical practice for treatment of infectious diseases, a single treatment dose is used for all patients. However, metabolism of drugs varies considerably between individuals, such that some individuals will have too high of drug levels—at risk of toxicity—while others at the same dose will have too low of drug levels and be at risk for treatment failure and drug-resistance. Inventors at Stanford developed a method that will inform the clinician about risks of toxicities and the appropriate dosing adjustments. In sum, this platform can inform what drug should be used, for what duration and at what dose, using a single patient sample.

The invention is a method for rapid detection of pharmacogenetic markers of antimicrobial metabolism and toxicity that will be performed concurrently with rapid detection of pathogens on the same sample. Clinical samples, such as blood, sputum and oral swab, typically have pathogen DNA as well as abundant human DNA present in them. This method uses molecular assays that target single nucleotide polymorphisms (SNPs) associated with drug metabolism and toxicity on a point-of-care testing platform. In a short time, this platform can report what pathogen is present, and what drug-metabolism markers are present in the patient.

Stage of Development
Proof of concept