NUS partners with FIND to discover novel biomarkers for tuberculosis detection

Singapore – 15 December 2011 – 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 diagnosis 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 of TB. This research is one of the early accomplishments of the new NUS SLING, which was established at the end of 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.

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¹Mycolic acids as diagnostic markers for tuberculosis case detection in humans and drug efficacy in mice (2011). Shui et al. EMBO Molecular Medicine http://onlinelibrary.wiley.com/doi/10.1002/emmm.201100185/abstract

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About the National University of Singapore (NUS) 
A leading global university centred in Asia, the National University of Singapore (NUS) is Singapore’s flagship university which offers a global approach to education and research, with a focus on Asian perspectives and expertise.

NUS has 16 faculties and schools across three campuses. Its transformative education includes a broad-based curriculum underscored by multi-disciplinary courses and cross-faculty enrichment. Over 36,000 students from 100 countries enrich the community with their diverse social and cultural perspectives.

NUS has three Research Centres of Excellence (RCE) and 21 university-level research institutes and centres. It is also a partner for Singapore’s 5th RCE. NUS shares a close affiliation with 16 national-level research institutes and centres. Research activities are strategic and robust, and NUS is well-known for its research strengths in engineering, life sciences and biomedicine, social sciences and natural sciences. It also strives to create a supportive and innovative environment to promote creative enterprise within its community.

For more information, please visit www.nus.edu.sg.

About NUS Enterprise
NUS Enterprise was established as a University-level cluster to provide an enterprise dimension to NUS teaching and research involving the University’s students, staff and alumni. The functions of the Enterprise Cluster complement the academic cluster of the University to nurture talents with an entrepreneurial and global mindset. NUS Enterprise promotes the spirit of innovation and enterprise through Experiential Education, Industry Engagement & Partnerships and Entrepreneurship Support. The NUS Industry Liaison Office is a division of NUS Enterprise. www.nus.edu.sg/enterprise.

About FIND
The Foundation for Innovative New Diagnostics is dedicated to developing affordable, easy-to-use and cutting edge diagnostic tests that save lives in the poorest areas of the world. From proof of principle to putting new tests into practice, the organization works with multiple and diverse groups, from academia, industry, donors, partners in the field, Ministries of Health and the World Health Organization. With five new diagnostic tools for TB already in use, FIND also has established programmes in malaria and sleeping sickness, and has begun working on other neglected diseases, such as leishmaniasis. Launched in 2003, the not-for-profit Foundation is ISO certified and financed by both the private and public sectors, including the Bill & Melinda Gates Foundation, Government of the Netherlands, the European Union, UNITAID, UK Department for International Development, National Institutes of Health (USA), UBS Optimus Foundation and others.

About National Research Foundation
The National Research Foundation (NRF), set up on 1 January 2006, is a department within the Prime Minister’s Office. The NRF sets the national direction for research and development (R&D) by developing policies, plans and strategies for research, innovation and enterprise. It also funds strategic initiatives and builds up R&D capabilities and capacities by nurturing local talents and attracting foreign ones. For more information, please visit www.nrf.gov.sg.

Annex A – About Tuberculosis and existing diagnostic methods
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. The disease remains a major global health threat, with over nine million new cases, and close to two million deaths, annually. In Singapore alone, some 1,500 new cases are detected each year, with foreigners accounting for over a third of these cases. The worldwide epidemic is further fuelled by co-infections with HIV, as well as the rapid emergence of drug-resistant strains of the TB bacteria.

Diagnosis of TB is primarily done by sputum smear microscopy, where a patient’s sputum sample is examined under a microscope for the presence of stained bacteria. This conventional method is over a hundred years old and has the disadvantages of being labour-intensive and having a poor sensitivity of less than 60 %. Furthermore, this method is extremely insensitive for extrapulmonary TB, TB in children and in patients with TB-HIV co-infection. Other TB diagnostic methods, which are more sensitive, can be expensive and it may take several days to weeks for the results to be delivered, thereby delaying initiation of treatment and increasing the risk of transmission.

Rapid, accurate and affordable diagnostic tests for TB are therefore urgently needed to fight the disease on a global basis.

Media enquiries may be directed to: 
Chan Yiu Lin
Greener Grass Communications (For NUS Enterprise)
Mobile: (65) 9-765 5897
Email: yiulin@greenergrass.com.sg

FIND
Email : media@finddx.org