Novartis sets up TB, dengue centre

The Novartis Institute for Tropical Diseases (NITD) is a $122 million (€99 million) public-private partnership between Novartis and the Singapore Economic Development Board (EDB). It aims to have at least two compounds in clinical trials by 2008 and two novel compounds available to patients by 2013. Novartis intends to make these treatments available without profit for countries where these diseases are endemic.

Located in the 2 million square feet Biopolis research complex, an integrated biomedical research hub located in Singapore, the discovery technology available at NITD includes target discovery and screen development, to compound optimisation, resulting in potential treatments ready for clinical testing. Its facilities also include nuclear magnetic resonance and DNA sequencing.

The NITD will employ 60 or 70 full time scientists and technicians and is the latest addition to the Novartis family worldwide. Singapore's high-quality science infrastructure and relative closeness to countries where TB and dengue fever are endemic make it an ideal location, according to the company.

As Professor Paul Herrling, head of Novartis corporate research and chairman of NITD explained: "Modern drug discovery really needs very close proximity to the patients it wants to treat. It is important to have direct access to patient tissues for scientific examination and to interact with treating doctors to understand the clinical needs of the patients."​

Today, more than one-third of the world's population is infected with TB and more than two million people die each year. In addition, 2.5 billion people worldwide are at risk from dengue fever. Drug resistant TB is responsible for more than 300,000 new cases per year occurring mainly in Eastern Europe and Central Asia.

The news that TB has increasingly become resistant to most of the antibiotics used today to treat the disease is worrying. Currently, more than 79 per cent of cases are identified as 'super strains,' resistant to three of the four current treatments. There has been little research into new treatment options for many years.

The present treatment for TB involves a complex 10-month course of four different antibiotics. However, bacterial resistance has increased because many patients, particularly in developing countries, do not receive the correct medications for the full course of treatment.

Advances in genomics have helped the identification of potential targets for new TB treatments. Comparative genomics has been used to study the evolution of the Mycobacterium tuberculosis​ bacteria.

Researchers have been trying to establish how the physical microenvironment of bacteria in vivo​ may limit exposure to antibiotic drugs. Identifying specific genes of the bacterium that manipulate the infected patients immune response plus those involved in virulence and spread of the disease is vital to the development of effective vaccines.

It is a similar story with dengue fever, with no major discovery effort directed to new treatments despite figures that suggest that it is long overdue. The World Health Organisation (WHO) cites 58,000 new cases of dengue fever in Indonesia alone during 2004 leading to 650 deaths. Worldwide, there are about 500,000 hospitalisations to treat dengue patients each year.

At present only supportive treatment for dengue fever patients is available. Antiviral medications offer much and advances in genetic research are aiding their development. Areas of the dengue genome involved in virus replication have been identified, and are potential targets for new broad acting anti-viral agents.

One particular area of promise is Acambis' ChimeriVax-Dengue vaccine. The "tetravalent" vaccine has shown in advanced pre-clinical trials to induce high levels of protective antibodies against all four dengue virus serotypes. There were no serious adverse events reported.