Institute of Microbiology (IMCAS), a member institute of the Chinese Academy of Sciences, and the Global Alliance for TB Drug Development (TB Alliance), a not-for-profit, product development partnership accelerating the discovery and development of new TB drugs, today announced a partnership to discover and develop promising, novel anti-tuberculosis agents from natural sources, including microbial metabolites and traditional Chinese medicines.
A pilot screen conducted by IMCAS identified 24 natural product extracts as having potential anti-tubercular activity. IMCAS and the TB Alliance will collaborate to further test these extracts, purify and identify the active components, and develop those that prove most promising. Additionally, IMCAS and the TB Alliance will work together to investigate the traditional Chinese herbal medicines and purified compounds for biological activity against the Mycobacterium tuberculosis (M.tb) organism. Scientists in China have made significant contributions in developing new drugs from natural sources, as exemplified by the identification of Artemisinin, one of the most effective anti-malarial drugs, first isolated from a traditional Chinese medicinal plant. The deficiency in natural product screening directly against M.tb combined with China's strong track record of successfully developing new drugs from traditional Chinese medicines, suggests such screenings are likely to yield novel active compounds.
Previously, a group of scientists including Professors Lixin Zhang, Deborah Hung and Eric Rubin from IMCAS, Broad Institute and Harvard University, respectively, worked together to investigate underlying mechanisms of M.tb, the bacterium that causes TB, with the intent to develop new TB drugs from natural sources to treat both drug-susceptible and drug-resistant TB. Modern technologies including high-throughput chemical screening, total genome sequencing, and the construction of systematic, comprehensive arrayed bacterial libraries were utilized in this process.
"This partnership reflects China's increasing commitment to address the deadly TB epidemic which has had such a devastating effect on so much of the world for so many years," said Dr. Mel Spigelman, President and CEO, TB Alliance. "Bringing the best science in China together with the expertise of the TB Alliance is an example of the pooling of global resources necessary to save the millions of lives needlessly lost to TB every year."
Novel drugs are needed to work against drug-resistant TB, the more deadly and difficult to treat form of TB that is on the rise across the globe, including in Asia. Drug resistance oftentimes emerges as a result of patients not completing the burdensome regimen currently used to treat drug-susceptible TB. The last class of new TB drugs was developed and approved in the 1960s. While the current treatment regimen for drug-susceptible TB is effective when administered properly, it must be administered over 6-9 months. Treatment for multidrug-resistant tuberculosis (MDR-TB) usually takes a minimum of 18 months and only cures approximately half of those infected. New, faster-acting TB treatments can improve treatment of both drug-sensitive and drug-resistant TB, enhance compliance, lower relapse rates, reduce the growth of drug-resistant TB, reduce health care costs and save millions of lives. The partnership between IMCAS and the TB Alliance is a fitting precursor to the three-day ministerial meeting of high MDR-/XDR-TB burden countries beginning tomorrow in Beijing.
"The fight against tuberculosis is a global endeavor. This partnership represents joint efforts by IMCAS and the TB Alliance in the development of new TB drugs from natural resources," said Prof. Li Huang, Executive Deputy Director-General of the IMCAS. "Natural products have long been an important source of drugs for human medicine. The rich functionality and stereochemistry of natural products is without doubt one of their great strengths, providing both potency and selectivity. Taking advantage of its expertise in the exploitation of microbial resources, IMCAS has recently set up the Drug Discovery Center for Tuberculosis. The aim of the Center, led by Prof. Lixin Zhang, is to develop and deliver novel TB drugs that work quickly and can help prevent the problems of today's drugs, relating to compliance, drug resistance and TB-HIV co-infection."
The TB Alliance is leading the development of the most comprehensive portfolio of TB drugs in history, and is accelerating discovery, preclinical and clinical research of known and novel classes of antibiotics to shorten and simplify the treatment of tuberculosis, including MDR- and XDR-TB. The TB Alliance is committed to making all drugs developed by its research partnerships affordable and available to all who need them.
About TB Disease
Tuberculosis, although usually potentially curable, continues to kill someone somewhere in the world about every 20 seconds - approximately 5,000 people every day, or 1.8 million in 2007 alone. TB is the leading infectious killer of adults, and the leading infectious cause of death among people with HIV/AIDS. It accounts for more deaths among women than all other causes of maternal mortality combined. The global economic toll of TB is at least $12 billion each year. The bacterium that causes TB can reside latently in the human body for many years, but once active, it frequently attacks the respiratory system, and is easily spread through the air like the common cold - by coughing and sneezing. The World Health Organization estimates that one third of the world is infected with TB.
Drug resistant strains of tuberculosis develop when the long, complex, decades-old TB drug regimen is not properly administered, or when patients stop taking their medicines before being fully cured. Once a drug-resistant strain has developed, it can be transmitted directly to others. Multidrug-Resistant TB (MDR-TB) is defined by resistance to the two most commonly used drugs in the current four-drug (or first-line) regimen, isoniazid and rifampin. MDR-TB has been reported in all regions of the globe and incidences are rising in many regions, including Asia. Treatment for MDR-TB is much more challenging, toxic, and expensive, and much less effective than treatment for drug susceptible TB. Extensively Drug Resistant TB (XDR-TB) is defined as MDR-TB that is also resistant to any fluoroquinolone, and at least one of three injectable second-line drugs. XDR-TB poses even greater challenges to treatment than MDR-TB; some strains of XDR-TB have proven virtually incurable with existing treatments