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Last Update: 2013-01-10   Source: Star Projects
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NM4TB – TB an enemy that dies hard

With tuberculosis (TB) making an unwelcome comeback in many developed countries – TB never really left the developing world – the news that EU-funded researchers are on the verge of a drug breakthrough is timely to say the least.

© Fotolia, 2012

Someone dies from TB every 15 seconds and 30 million more people will succumb to this deadly bacterium in the coming decade if new treatments are not found.

Once known as 'consumption' for the way it 'consumed' the lungs and sometimes other organs, TB is one of the oldest known infectious diseases. Its agent Mycobacterium tuberculosis has already infected a third of the world's population, and this is despite decades of vaccination programmes!

Yes, treatments do exist – Directly observed short course chemotherapy (DOTS) is widely available – but experts now consider them "old, slow and inefficient". What's more, the emergence of multi-drug resistant strains in high-burden countries, but especially in Europe, is cause for added concern.

"In fact, we've seen a high correlation between the global HIV epidemic and the spread and resurgence of TB," says Professor Stewart Cole, chief scientist in the EU-backed NM4TB project and head of the Cole Lab at the École Polytechnique Fédérale de Lausanne, Switzerland.

There are good reasons for this shared trajectory. Left unchecked, TB multiplies in the lungs until pneumonia sets in, causing chest pain, prolonged coughing and bloody phlegm. The body's immune system usually prevents the bacteria from spreading to other parts of the body, or people. But if the immune system is weakened, for example by HIV, the bacteria breaks free of the coating (scar tissue) that isolates it and the disease re-establishes in the lungs and elsewhere – kidneys, bones, spinal, brain … other people.

It is the perfect storm, according to scientists who are pitted in a battle to defeat TB once and for all. But thanks to significant public and private funding in projects like New medicines for tuberculosis (NM4TB) and its successor project which runs until 2016, there is hope. They have already identified novel approaches to identify and validate targets for potent new TB drugs capable of cutting treatment time while combatting persistent bacilli and multi-drug resistant strains.

Promising leads
NM4TB ran an ambitious drug-discovery project that combined some of Europe's leading academic TB researchers with a major pharmaceutical company (Astra-Zeneca) and three small and medium-sized enterprises (SMEs) – all with a strong commitment to discovering new anti-infective agents.

The 66-month, multi-million euro project delivered a comprehensive portfolio of potential and validated targets plus several novel, proprietary anti-TB agents in its drug development pipeline.

NM4TB discovered benzothiazinones, the most potent drug candidates yet described against TB, and BTZ043 has nearly completed preclinical development so it should reach clinical trials shortly. According to an NM4TB statement, their results were published in the journal Science.

The continuity of the research for nearly a decade has been a critical factor in building momentum which is culminating in new life-saving drugs: "This is a good funding model for future drug-discovery programmes for global diseases of poverty, such as TB, which are often neglected by commercial R&D programmes. Subsequent clinical trials of this new drug in people with TB must be fully funded to finally realise the potential of our scientific effort," confirms project partner Professor Philip Butcher of St George's University of London, in a statement.

In the follow-up project – More medicines for tuberculosis (MM4TB) – the addition of several new academic partners, two SMEs and the Sanofi-Aventis R&D shows a strong and continuing commitment to the discovery of anti-infective agents. The consortium is working on new drugs to keep not one but two steps ahead of this ancient foe.


Project details

  • Participants:Switzerland (Coordinator) Hungary, UK, Sweden, India, Russia, Slovenia, Italy, France, Germany, Denmark, Spain, South Africa
  • Project N° 18923
  • Total costs: € 12 879 968
  • EU contribution: € 11 070 000
  • Duration: January 2006 to June 2011

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