FIND, NUS collaborate to identify novel biomarkers for TB diagnosis

A research team from the National University of Singapore (NUS) Singapore Lipidomics Incubator (SLING) is collaborating with the Foundation for Innovative New Diagnostics (FIND) to identify novel target molecules to be employed as biomarkers for the detection of active tuberculosis (TB). The aim is to translate these targets into a diagnostic test that is affordable, easy to use and produces rapid results, and that can be used by community health workers in poor countries.

Scientists have attempted to develop a simple and accurate antigen test to detect TB for many years, with little success. The World Health Organization (WHO) has yet to endorse any such test, since it has not deemed that any of the existing examples are of sufficient accuracy for clinical use. The major reason for this failure is the lack of suitable TB-specific biomarkers for diagnostic product development. So far, only a very limited number of antigens have been investigated for this purpose.

"A sensitive, pathogen-specific, point-of-care test for TB case detection would represent a breakthrough in TB diagnostics for disease endemic settings, but we have so far been hampered by a lack of appropriate biomarkers," said Dr Gerd Michel, Senior Technology Officer at FIND, who is FIND's project leader. "Through our partnership with NUS, we aim to address this fundamental gap by developing high performance reagents, which we will be able to then convert into a laboratory-free rapid test for TB."

The technology supported by this partnership is based on research conducted by Associate Professor Markus Wenk, Principal Investigator at NUS SLING, and his team. This revealed that certain mycolic acids - molecules found on the cell wall of Mycobacterium tuberculosis (the bacterium causing TB) - are specific TB disease markers. The study analysed sputum samples from close to 200 individuals with pulmonary TB, some of whom were also infected with HIV. These samples were obtained from patients and endemic controls in South Korea, Vietnam, Uganda and South Africa, i.e. countries with a significant burden of TB.

The NUS research team used high resolution mass spectrometry to determine the precise bacterial remnant in sputum. Based on this analysis, they were able to separate non-TB patients from those with active TB infection, with diagnostic results better than the most widely used TB diagnostic test - sputum smear microscopy (see Annex A for more information on TB and current diagnostics).

The high resolution mass spectrometry methodology is complementary to existing TB diagnostics, and is also fast, providing results within a day. The team also revealed in a preclinical study that their methodology could distinguish between active TB cases and cases that had been cured from TB. This research is one of the early accomplishments of the new NUS SLING, which was established in end 2010. The research data from this study are due to be published in a leading scientific journal, EMBO Molecular Medicine. The study was funded by the National Research Foundation of Singapore and the Novartis Institute of Tropical Diseases.

"This study is an excellent example of translational research. First, basic biomedical investigation is integrated with current medical practice to assess the potential clinical utility of a new biomarker. We then use the results to convert a technology platform developed at NUS into a commercial diagnostic product, thus translating basic science into medical practice. In this case, now that we have successfully identified mycolic acids as a marker for TB infection, we plan to work with the NUS Department of Microbiology to develop antibodies specific to mycolic acid for detection by immunoassay," said Assoc Prof Markus Wenk, who is also from the NUS Department of Biochemistry and Department of Biological Sciences.

While NUS will focus on the technology development of the diagnostic test, FIND will provide their extensive expertise in diagnostic product development. If successfully developed, this test would enter evaluation and demonstration studies, and then be submitted for endorsement by the WHO, before being rolled out in TB-endemic countries. The NUS Industry Liaison Office has filed a patent application for the technology, and also facilitated the research and license agreements.

"Given the worldwide rise of multidrug-resistant TB, I strongly welcome any new test that is able to accurately diagnose TB. I believe it would be equally interesting to see if this molecular marker can accurately reflect clearance of the bacteria from the lungs, in order to monitor treatment response in patients," said Dr Timothy Barkham, Director, The Molecular Biology Laboratory, Tan Tock Seng Hospital.


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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