PEPCK (phosphoenolpyruvate carboxykinase) a potential target for drugs that fight tuberculosis.

 In continuation of my update on tuberculosis and drug discovery ..... A new  research conducted at Weill Cornell Medical College sheds light on a previously unrecognized aspect of fatty acid metabolism that could potentially lead to new targets for drug therapy. A team led by Dr. Sabine Ehrt, professor of microbiology and immunology at Weill Cornell Medical College, reported that Mtb relies primarily on gluconeogenic substrates for in vivo growth and persistence, and that phosphoenolpyruvate carboxykinase (PEPCK see picture) plays a pivotal role in the growth and survival of Mtb during infections in mice, making PEPCK a potential target for drugs that fight tuberculosis.

Dr. Ehrt and her colleagues found a way to silence the gene encoding PEPCK in Mtb during mouse infections to assess the importance of gluconeogenesis for Mtb's ability to maintain a chronic infection.

 "Silencing a gene when the pathogen is not or only slowly replicating, after an infection has established, is an important tool for studying diseases such as TB, which can be dormant for years only to become active again years later." says Dr.Ehrt...

 It is especially challenging as the infection can lay dormant in the body even though there are no symptoms. Researchers investigated the metabolic requirements of Mtb during acute and chronic infections and found that the gluconeogenic enzyme PEPCK is critical for both.

Interestingly, the  study used a novel mass spectrometry-based metabolic profiling tool, developed at Weill Cornell (in collaboration with Agilent Technologies) by Dr. Kyu Rhee to biochemically examine Mtb carbon metabolism. As per the claim by the researchers,  the tool has provided the first direct insights into the metabolic architecture of Mtb.

 Though the current treatments used  to treat Mtb are effective, the treatment times are too long and the regimens too complex, which  leads to treatment failures (due to poor adherence and multi drug resistance).   We need new, safer drugs that work faster to eliminate tuberculosis.  Dr. Ehrt hopes that her work will eventually lead to new drug therapies to treat tuberculosis.....

Ref : http://www.pnas.org/content/early/2010/04/26/1000715107

Combination of bedaquiline and verapamil reduces side effects, improves outcomes for TB patients

In continuation of my update on Bedaquiline

While an effective treatment is available for combating multidrug-resistant tuberculosis, it carries serious side effects for patients. New research conducted at the Center for Tuberculosis Research at the Johns Hopkins University School of Medicine shows that lower doses of the toxic drug bedaquiline — given together with verapamil, a medication that's used to treat various heart conditions — can lead to the same antibacterial effects as higher toxic doses of bedaquiline. The combination of the two drugs could potentially shorten treatment time, reduce the side effects of bedaquiline and improve patient outcomes for those suffering from TB.

The study will be published in the January 2014 issue of Antimicrobial Agents and Chemotherapy. The lead author is William Bishai, M.D., Ph.D., co-director of the Center for Tuberculosis Research.

"Using a mouse model of tuberculosis, we have shown lower doses of bedaquiline together with verapamil have the same antibacterial effect as the higher toxic doses," says Shashank Gupta, Ph.D., a research fellow at Johns Hopkins. "A lower dose of bedaquiline will cause no or less severe side effects."

Two years ago, bedaquiline became the first drug in the last four decades to be approved by the U.S. Food and Drug Administration for the treatment of multidrug-resistant TB. The drug works by inhibiting an enzyme used by Mycobacterium tuberculosis to replicate and spread throughout the body. While it can be a lifesaving therapy against one of the world's deadliest diseases, bedaquiline can also cause serious side effects in the heart and liver. Therefore, strategies to reduce the dose of bedaquiline while retaining its antibacterial activity would provide significant benefits to patients.

"Shortening treatment regimens and reducing the required doses may be a promising strategy to reduce the incidence of bedaquiline-related adverse effects and thereby improve multidrug-resistant TB treatment outcomes," says Gupta.

Combination of bedaquiline and verapamil reduces side effects, improves outcomes for TB patients

LXR Proteins- New target for antitubercular activity?

As we are aware that TB, has become a major threat to the world and a recent study also reports an estimated one-third of the world population is latently infected with Mycobacterium tuberculosis. And also I did mention (earlier blog) that the strain has got resistance for drugs Rifampicin and hence comibination of drugs (Rifampicin, Isoniazid, Euthumbutol) is being used. The most worst part of this is for those who are already infected with HIV. Not only these are the facts of concern, the worst part of this bacterium is "M. tuberculosis has the ability to adapt and survive for long periods of time within the host macrophage in a state of clinical dormancy". The researchers attribute the reason for this as the switching to lipids as their main carbon source of the nutrient-deficient macrophage phagosome. A recent report implicated that mycobacterial persistence is critically linked to its ability to acquire and catabolize cholesterol from the host. Cholesterol, besides being used as an energy or carbon source, is also essential for the phagocytosis of the bacterium by the macrophage and for the inhibition of phagosome maturation. Recently, liver X receptors (LXRs), LXRα and LXRβ, have emerged as master regulators of macrophage transcriptional programs involved in cholesterol, fatty acid, and glucose homeostasis. All these facts encouraged Kris Huygen and colleagues of Scientific Institute of Public Health, Belgium to identify the role of LXR proteins in the mouse immune response to airway infection with Mycobacterium tuberculosis.

In the study, when compared with normal mice, mice lacking both forms of LXR (LXR-alpha and LXR-beta) were more susceptible to airway infection with Mycobacterium tuberculosis and developed more severe disease. Further analysis revealed that these mice did not mount an effective immune response in the airways. There was no accumulation of immune cells (neutrophils) in the lungs and little evidence of Th1 and Th17 immune responses. Importantly, the marked protection from infection seen in normal mice treated with molecules that target LXRs was accompanied by increased Th1 and Th17 immune responses.

Congrats Kris for this achievement. More...

FDA Approves Sirturo to Treat Multi-Drug Resistant Tuberculosis

In continuation of my update on bedaquiline...

Sirturo is being approved under the FDA’s accelerated approval program, which allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. This program provides patients earlier access to promising new drugs while the company conducts additional studies to confirm the drug’s clinical benefit and safe use.

The FDA also granted Sirturo fast track designation, priority review and orphan-product designation. The drug demonstrated the potential to fill an unmet medical need, has the potential to provide safe and effective treatment where no satisfactory alternative therapy exists, and is intended to treat a rare disease, respectively.

Sirturo carries a Boxed Warning alerting patients and health care professionals that the drug can affect the heart’s electrical activity (QT prolongation), which could lead to an abnormal and potentially fatal heart rhythm. The Boxed Warning also notes deaths in patients treated with Sirturo. Nine patients who received Sirturo died compared with two patients who received placebo. Five of the deaths in the Sirturo group and all of the deaths in the placebo arm seemed to be related to tuberculosis, but no consistent reason for the deaths in the remaining Sirturo-treated patients could be identified.

Sirturo’s manufacturer, Janssen Therapeutics, will distribute the drug from a single source and will provide educational materials to help ensure the drug is used appropriately.

Sirturo’s safety and effectiveness were established in 440 patients in two Phase 2 clinical trials. Patients in the first trial were randomly assigned to be treated with Sirturo plus other drugs used to treat TB, or a placebo plus other drugs used to treat TB. All patients in the second trial, which is ongoing, received Sirturo plus other TB drugs. Both studies were designed to measure the length of time it took for a patient’s sputum to be free of M. tuberculosis (sputum culture conversion, or SCC).

FDA Approves Sirturo to Treat Multi-Drug Resistant Tuberculosis

Diospyrin inactivates a drug target for tuberculosis in new way

A compound from the South African toothbrush tree inactivates a drug target for tuberculosis in a previously unseen way. 

The compound under research, diospyrin (see below structure), binds to a novel site on a well-known enzyme, called DNA gyrase, and inactivates the enzyme. DNA gyrase is essential for bacteria and plants but is not present in animals or humans. It is established as an effective and safe drug target for antibiotics.

"The way that diospyrin works helps to explain why it is effective against drug-sensitive and drug-resistant strains of tuberculosis," said Professor Tony Maxwell from the John Innes Centre.

In traditional medicine the antibacterial properties of the tree are used for oral health and to treat medical complaints such bronchitis, pleurisy and venereal disease. Twigs from the tree are traditionally used as toothbrushes.

Most antibiotics originate from naturals sources, such as the soil bacteria Streptomyces. Antibiotics derived from plants are less common, but they are potentially rich sources of new medicines.

"Extracts from plants used in traditional medicine provide a source for novel compounds that may have antibacterial properties, which may then be developed as antibiotics," said Professor Maxwell.

Diospyrin inactivates a drug target for tuberculosis in new way

Ancient Chinese medicine for malaria could potentially aid in treatment of tuberculosis

In continuation of my update on Artemisinin

A centuries-old herbal medicine, discovered by Chinese scientists and used to effectively treat malaria, has been found to potentially aid in the treatment of tuberculosis and may slow the evolution of drug resistance.

In a promising study led by Robert Abramovitch, a Michigan State University microbiologist and TB expert, the ancient remedy artemisinin stopped the ability of TB-causing bacteria, known as Mycobacterium tuberculosis, to become dormant. This stage of the disease often makes the use of antibiotics ineffective.

The study is published in the journal Nature Chemical Biology.

"When TB bacteria are dormant, they become highly tolerant to antibiotics," Abramovitch said, an assistant professor in the College of Veterinary Medicine. "Blocking dormancy makes the TB bacteria more sensitive to these drugs and could shorten treatment times."

One-third of the world's population is infected with TB and the disease killed 1.8 million people in 2015, according to the Centers for Disease Control and Prevention.

Mycobacterium tuberculosis, or Mtb, needs oxygen to thrive in the body. The immune system starves this bacterium of oxygen to control the infection. Abramovitch and his team found that artemisinin attacks a molecule called heme, which is found in the Mtb oxygen sensor. By disrupting this sensor and essentially turning it off, the artemisinin stopped the disease's ability to sense how much oxygen it was getting.

"When the Mtb is starved of oxygen, it goes into a dormant state, which protects it from the stress of low-oxygen environments," Abramovitch said. "If Mtb can't sense low oxygen, then it can't become dormant and will die."

Abramovitch indicated that dormant TB can remain inactive for decades in the body. But if the immune system weakens at some point, it can wake back up and spread. Whether it wakes up or stays 'asleep' though, he said TB can take up to six months to treat and is one of the main reasons the disease is so difficult to control.

"Patients often don't stick to the treatment regimen because of the length of time it takes to cure the disease," he said. "Incomplete therapy plays an important role in the evolution and spread of multi-drug resistant TB strains."

He said the research could be key to shortening the course of therapy because it can clear out the dormant, hard-to-kill bacteria. This could lead to improving patient outcomes and slowing the evolution of drug-resistant TB.

After screening 540,000 different compounds, Abramovitch also found five other possible chemical inhibitors that target the Mtb oxygen sensor in various ways and could be effective in treatment as well.

"Two billion people worldwide are infected with Mtb," Abramovitch said. "TB is a global problem that requires new tools to slow its spread and overcome drug resistance. This new method of targeting dormant bacteria is exciting because it shows us a new way to kill it."

Ref : http://www.nature.com/nchembio/journal/vaop/ncurrent/full/nchembio.2259.html

Novel two-drug combination cures young patient with extensively drug-resistant tuberculosis

The combination of meropenem (above structure)  with clavulanate (right structure-potassium salt)  has high antimycobacterial activity in vitro against extensively drug-resistant Mycobacterium tuberculosis strains. Researchers report the successful use of this combination in association with linezolid (below structure)  in the management of an advanced extensively drug-resistant tuberculosis disease with complex second-line drug resistance in a 14-year-old teenager.

Ref : 1.Meropenem/Clavulanate and Linezolid Treatment for Extensively Drug-Resistant Tuberculosis

    2. http://www.einstein.yu.edu/uploadedFiles/PHD/2010%20Faculty%20Research%20Book.pdf

Researchers identify potential way to combat TB

Researchers have identified a potential way to manipulate the immune system to improve its ability to fight off tuberculosis (TB).

TB is a major problem for both humans and cattle and the new findings could help scientists to create better drugs to combat the disease in both.

The disease is caused by the bacterium Mycobacterium tuberculosis, which infects the lungs. The mycobacteria are able to establish persistent TB infections by taking up residence in macrophages - cells of the immune system that would normally destroy invading microorganisms.

Now, in early stage research published in the Journal of Biological Chemistry, researchers from Imperial College London and Stanford University have revealed precisely how unusual sugars on the surface of the mycobacteria that cause TB are able to latch onto the macrophages and disarm them. They now hope that scientists at Imperial and elsewhere can use this knowledge to develop small molecule drugs that latch tightly onto the same site.

These drugs could potentially fight tuberculosis in a number of ways, say the researchers. They could create a barrier to prevent the mycobacteria from attaching to the macrophages; they could transport drugs to kill the mycobacteria; or they could change how the macrophages behave, so that they destroy the mycobacteria rather than harbouring them.

Professor Kurt Drickamer, a lead author of the research from the Department of Life Sciences at Imperial College London, said: "TB is hard to fight effectively because it can hide inside the cells of the immune system that should be able to destroy it. We were surprised to find that there is an extensive interaction between the macrophage and one particular type of molecule on the surface of the mycobacteria. The nature of the interaction gives us hope that we can make simple molecules that block the ability of the mycobacteria to subvert the macrophages.

Ref : http://www.jbc.org/content/288/40/28457.abstract?sid=eeb4801e-b429-4bbf-b0cd-446229088668

"Researchers identify potential way to combat TB

Diabetes drug can boost efficacy of TB medication without causing drug resistance

In continuation of my update on Metformin

A more effective treatment for tuberculosis (TB) could soon be available as scientists have discovered that Metformin (MET), a drug for treating diabetes, can also be used to boost the efficacy of TB medication without inducing drug resistance.

This discovery was made by a team of international scientists led by the Singapore Immunology Network (SIgN), a research institute under the Agency for Science, Technology and Research (A*STAR), Singapore.

TB is an air-borne infectious disease caused by a bacterium called Mycobacterium tuberculosis (Mtb), which often infects the lungs. Even though drugs are available to treat the disease, TB continues to be a major threat to public health, killing close to 1.5 million people every year .

Conventional drugs used to treat TB usually adopt a pathogen-targeted strategy which attacks and kills bacteria directly. This approach has caused Mtb strains to acquire drug resistance, making existing treatments become increasingly ineffective and resulting in a pressing need to design new therapeutic strategies for the disease.

MET as an adjunct treatment for TB

The team of scientists led by SIgN began searching for drugs that could control Mtb replication indirectly. They screened FDA-approved drugs and identified MET, an old anti-diabetic drug that could defend Mtb invasion without targeting the bacteria directly. Instead, MET targets the host cells to trigger the production of a chemical which then damages Mtb and stops its replication. Such indirect, host-targeted approach is less likely to engender drug resistance. The team also discovered that MET improves the efficacy of conventional anti-TB drugs when used in combination with them.

The scientists then validated the findings with patient data provided by the Tuberculosis Clinical Unit at the Tan Tock Seng Hospital, and consequently verified that the use of MET is indeed associated with improved TB control and decreased disease severity. This anti-diabetic drug is therefore a promising adjunctive therapy that could enhance the effectiveness of existing TB treatments. As it is a drug that is currently in use, another benefit of using MET as an adjunct treatment for TB is that it is likely to shorten the time required for clinical trials.

Diabetes drug can boost efficacy of TB medication without causing drug resistance

PA-824 - Aerosol: New Tool Against Tuberculosis?

We know the epidemic rates of HIV/TB coinfection as well as emerging multidrug-resistant  (MDR) and extensively drug-resistant (XDR) TB strains those are contributing to increased TB-associated deaths worldwide. 

Now PA-824 (see structure), a compound capable of being formulated into a dry powder, has not only shown promising activity against MDR (multidrug-resistant tuberculosis) and XDR (extensively drug-resistant tuberculosis, or latent TB) but has also proven safe and effective in patients coinfected with HIV and TB. Previous studies showed that PA-824 was well-tolerated in tablet form, however, side effects such as headache and stomach discomfort were reported. Aerosol delivery of PA-824 directly to the primary site of infection would limit systemic exposure and ultimately eliminate potentially bothersome side effects.

About  PA-824 :

Nitroimidazoles are widely used drugs in humans for a variety of primarily anaerobic microbial infections. Metronidazole, a 5-nitroimidazole, is an important bactericidal agent for the treatment of anaerobic infections  and shows excellent selective toxicity toward anaerobic bacterial and protozoal pathogens. This class of compounds has only recently begun to be explored for Mtb, because only anaerobic activity of metronidazole against Mtb has been reported. Bicyclic 4-nitroimidazoles such as PA-824 (a nitroimidazo-oxazine) and CGI-17341 (a nitroimidazo-oxazole) have inhibitory activity against aerobically growing and nonreplicating anaerobic Mtb. Although anaerobic conditions have not been demonstrated during TB disease in humans, various authors have suggested that an anaerobic microenvironment may contribute to a nonreplicating state that may be linked with latent disease in humans. Thus, PA-824 has been developed, in part, because it may be a promising lead for therapy against latent disease that may be linked to anaerobically persisting bacilli. The Global Alliance for TB Drug Development has recently initiated phase-I clinical trials with PA-824 

Researchers from the University of North Carolina School of Pharmacy, Chapel Hill, North Carolina; and Harvard School of Engineering and Applied Sciences, Cambridge, Massachusetts, lead by  Dr. Anthony J Hickey  have achieved this interesting finding, i.e., potential use of PA-824 dry powder aerosols in the treatment of TB.

In the study guinea pigs were used to evaluate the effects of PA-824 aerosols on TB infection. One month following infection with TB some guinea pigs received high daily aerosol treatments while others received low daily treatments for 4 weeks. Lung and spleen analysis of guinea pigs receiving the high dose of aerosol PA-284 showed less inflammation, bacterial burden and tissue damage.

"The present studies indicate the potential use of PA-824 dry powder aerosols in the treatment of TB,” say the researchers".

Ref : http://aac.asm.org/cgi/content/abstract/54/4/1436.

FDA Approves Pretomanid for Highly Drug-Resistant Forms of Tuberculosis

In continuation of my update on Pretomanid

 Pretomanid, a novel compound developed by the non-profit organization TB Alliance, was approved by the U.S. Food & Drug Administration (FDA) today for treating some of the most drug-resistant forms of tuberculosis (TB).1 The new drug was approved under the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD pathway) as part of a three-drug, six-month, all-oral regimen for the treatment of people with extensively drug-resistant TB (XDR-TB) or multidrug-resistant TB (MDR-TB) who are treatment-intolerant or non-responsive (collectively “highly drug-resistant TB”).1,2

The LPAD pathway was established by FDA as a tool to encourage further development of antibacterial and antifungal drugs to treat serious, life-threatening infections that affect a limited population of patients with unmet needs. 

“FDA approval of this treatment represents a victory for the people suffering from these highly drug-resistant forms of the world’s deadliest infectious disease,” said Mel Spigelman, MD, president and CEO of TB Alliance. “The associated novel regimen will hopefully provide a shorter, more easily manageable and highly efficacious treatment for those in need.”

The three-drug regimen consisting of bedaquiline, pretomanid and linezolid – collectively referred to as the BPaL regimen – was studied in the pivotal Nix-TB trial across three sites in South Africa. The trial enrolled 109 people with XDR-TB as well as treatment-intolerant or non-responsive MDR-TB.2

Nix-TB data have demonstrated a successful outcome in 95 of the first 107 patients after six months of treatment with BPaL and six months of post-treatment follow-up.2 For two patients, treatment was extended to nine months. The new drug application contains data on 1,168 people who have received pretomanid in 19 clinical trials that have evaluated the drug’s safety and efficacy.2 Pretomanid has been clinically studied in 14 countries.

TB, in all forms, must be treated with a combination of drugs; the most drug-sensitive forms of TB require six months of treatment using four anti-TB drugs.3 Treatment of XDR-TB or treatment-intolerant/non-responsive MDR-TB has historically been lengthy and complex; most XDR-TB patients currently take a combination of as many as eight antibiotics, some involving daily injections, for 18 months or longer.3,4 Prior to recent introduction of new drugs for drug-resistant TB, the World Health Organization (WHO) has reported estimates for treatment success rates of XDR-TB therapy at approximately 34 percent and about 55 percent for MDR-TB therapy.4

“Until very recently, people infected with highly drug-resistant TB had poor treatment options and a poor prognosis,” said Dr. Francesca Conradie, principal investigator of the Nix-TB trial. “This new regimen provides hope with 9 out of 10 patients achieving culture negative status at 6 months post-treatment  with this short, all-oral regimen."

Pretomanid is a new chemical entity and a member of a class of compounds known as nitroimidazooxazines. TB Alliance acquired the developmental rights to the compound in 2002. It has been developed as an oral tablet formulation for the treatment of TB in combination with bedaquiline and linezolid, two other anti-TB agents, and is now indicated for use in a limited and specific population of patients.1 Adverse reactions reported during the Nix-TB trial of the BPaL regimen include hepatotoxicity, myelosuppression, as well as peripheral and optic neuropathy.1 Please see additional safety information in the Important Safety Information below.

Pretomanid is only the third new anti-TB drug approved for use by FDA in more than 40 years, as well as the first to be developed and registered by a not-for-profit organization.5,6 Pretomanid was granted Priority Review, Qualified Infectious Disease Product, and Orphan Drug status. As a product development partnership, TB Alliance has collaborated with and received significant support from numerous governments, academia, philanthropic institutions, the private sector, civil society organizations and other partners over the course of pretomanid’s development.

Pretomanid is expected to be available in the United States by the end of this year. In addition to the U.S. FDA, TB Alliance has submitted pretomanid as part of the BPaL regimen for review by the European Medicines Agency and has provided data to the World Health Organization for consideration of inclusion in treatment guidelines for highly drug-resistant TB.

https://en.wikipedia.org/wiki/Pretomanid

Immunitor reports positive safety imm01 clinical trial against tuberculosis

Immunitor reports positive safety imm01 clinical trial against tuberculosis

Tuberculosis Patients Can Reduce Transmissability By Inhaling Interferon Through A Nebulizer

As for as my knowledge goes "Interferons" - (glycoproteins - natural cell-signaling proteins produced by the cells of the immune system of most vertebrates in response to challenges such as viruses, parasites and tumor cells).

1.  assist the immune response by inhibiting viral replication within host cells, activating natural killer cells and macrophages, increasing antigen presentation to T lymphocytes.

2. increasing the resistance of host cells to viral infection.

And are said to possess the antiviral and antitumour activity.   

But this finding is really interesting.................."Tuberculosis Patients Can Reduce Transmissability By Inhaling Interferon Through A Nebulizer" 

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Body's own proteins may lead the way in global fight against tuberculosis

Body's own proteins may lead the way in global fight against tuberculosis

Increase in Rifampicin dosage shortens tuberculosis treatment duration !

Increase in Rifampicin dosage shortens tuberculosis treatment duration

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Experimental drug tested against multi-drug resistant TB

"Researchers who tested a novel type of antibiotic against multi-drug-resistant tuberculosis [MDR-TB] are reporting that nearly half of patients who got the new drug cleared the bacteria from their lung fluid in two months," according to a study published  in the New England Journal of Medicine. Japanese pharmaceutical company Otsuka developed the experimental drug, delamanid (see structure), and "also designed and financed the clinical trial, which took place in 17 medical centers across nine countries." 

 "'We've invested a lot of time and money to develop this drug, but we are not seeking robust sales growth immediately,' Masuhiro Yoshitake, Otsuka's head of tuberculosis projects, said in an interview," Bloomberg Businessweek reports. "We want to begin selling to people who know how to use the drug," he added, the news service notes. "Doctors must balance the need to fight hard-to-treat cases against prolonging the medicine's potency,"

More : http://www.nejm.org/doi/full/10.1056/NEJMoa1112433

Experimental drug tested against multi-drug resistant TB

New research finding may change direction of vaccine research for M. tuberculosis

New research finding may change direction of vaccine research for M. tuberculosis

New details of tuberculosis protein-cleaving machinery revealed

New details of tuberculosis protein-cleaving machinery revealed

New Vaccine for TB...!

We are aware that TB has become one of the most dangerous disease (more than two billion people are infected with tuberculosis – approximately one out of every three people on the planet – and 1.8 million die annually from the disease). And also the strain is getting resistance to the single drug and a combination of Rifampicin, Ethumbutol, Isoniazid and Streptomycin a combo of 4 drugs is being used as treatment. And as per the saying "Prevention is better than Cure", a new vaccine is urgently needed, as BCG is currently the only available vaccine against TB, and provides only variable protection against pulmonary tuberculosis, which accounts for most of the worldwide disease burden. Now thanx to Dr Helen McShane, a Wellcome Trust Senior Clinical Research Fellow, working with Dr Sarah Gilbert, a Reader in Vaccinology, and Professor Adrian Hill, a Wellcome Trust Principal Research Fellow- who together achieved a milestone in developing the vaccine and it has entered Phase IIb proof-of-concept clinical trials, making it the first TB candidate vaccine for more than 80 years to get to this advanced stage of clinical trials in infants. There is still a long road ahead, but this marks an important milestone toward the goal of a more effective TB vaccine. First I congratulate for this milestone and wish them all the success in their attempt.

Ref : http://www.ox.ac.uk/media/news_stories/2009/090423.html

Tuberculosis Survival Mechanism Identified ?

Inhibitors Of Important Tuberculosis Survival Mechanism Identified

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