Hope for powerful new C. Difficile treatment

Sunday 22 September 2013

Islamabad, Sep 23 (Newswire): MGB Biopharma, a biopharmaceutical company which has licensed technology from the University of Strathclyde in Glasgow, Scotland, is developing a powerful new antibiotic treatment for resistant infections including the deadly MRSA and Clostridium difficile (C. diff.) bugs.

The Glasgow-based company is working on a new compound which has proved to be more effective in killing and preventing C diff. than vancomycin, currently one of the most widely used treatments against this bacterium.

The company has selected the compound, MGB BP-3, as a drug candidate for formal pre-clinical development, with clinical trials now scheduled for 2012.

The compound acts in minor grooves, found within DNA structures, and has potential to act as an agent against bacteria including C. diff. and MRSA.

C. diff. was involved in more than 3,000 deaths in the UK in 2010.
The findings of the research are being presented Sept. 19 at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), held in Chicago.

Dr Miroslav Ravic, Chief Executive Officer of MGB Biopharma, said: "It seems we are hearing too much about Clostridium difficile infections these days in the press, especially those acquired in hospital by elderly patients in whom the infection can be fatal.

"This is clearly an area of high unmet need as a result of the rise of resistant bacteria which are threatening to outpace the availability of new drugs able to successfully treat these life- threatening infections. We are very excited that MGB BP-3 shows such a promising response against this troublesome and difficult to treat infection.

"We are committed to developing a specific oral drug for the treatment of Clostridium difficile infections in addition to the progress we are making with an IV drug against MRSA."

Professor Colin Suckling, of the University of Strathclyde's Department of Pure and Applied Chemistry, is Principal Investigator in the DNA minor groove binder technology. He said: "C. diff. infections can kill and patients can face prolonged courses of treatment to deal with them.

"We have come up with strong compounds which are capable not only of clearing the infections but also of stopping them. We believe this could be a significant step forward in tackling these dangerous infections."

Professor Curtis Gemmell, Consultant Microbiologist, Research Professor at the Strathclyde Institute of Pharmacy and Biomedical Sciences and Emeritus Professor at the University of Glasgow, is a senior member of the research team. He said: "The fact that our drug candidate shows greater efficacy than vancomycin is extremely promising for its future. The fact we are making this presentation at ICAAC underscores the importance that our scientific peers attach to our findings."

MGB Biopharma's technology was licensed from the University of Strathclyde, with the licensing negotiated by the University's Research & Knowledge Exchange Services. The company has been financed by a business angel syndicate led by Archangel Informal Investments Ltd in association with TriCapital Ltd, Barwell plc and the Scottish Co-investment Fund.

Professor Suckling and Professor Gemmell are members of MGB Biopharma's Joint Development Committee.

Strathclyde Institute of Pharmacy and Biomedical Sciences is a pioneering centre for developing new medicines for illnesses and conditions including infectious diseases, cancer, heart disease and arthritis. An £8 million fundraising campaign is underway for the Institute's new £36 million building, to expand and enhance its innovative medical research, education and discovery capabilities to continue providing solutions to major health care problems.

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Biodiversity loss may be contributing to amphibian-killing fungal infection

Islamabad, Sep 23 (Newswire): Researchers at Oregon State University have shown for the first time that loss of biodiversity may be contributing to a fungal infection that is killing amphibians around the world, and provides more evidence for why biodiversity is important to many ecosystems.

The findings, being published in Proceedings of the National Academy of Sciences, used laboratory studies of amphibians to show that increased species richness decreased both the prevalence and severity of infection caused by the deadly chytrid fungus, Batrachochytrium dendrobatidis.

"With greater diversity of species, you get a dilution effect that can reduce the severity of disease," said Catherine Searle, an OSU zoologist and lead author on the study. "Some species are poor hosts, some may not get infected at all, and this tends to slow disease transmission.

"This has been shown in other systems like Lyme disease which infects humans, mice and deer," she said. "No one has really considered the dilution effect much in amphibians, which are experiencing population declines throughout the world. It's an underappreciated value of biodiversity."

It's generally accepted, the researchers said, that a high diversity of species can protect ecosystem function, help to recycle nutrients, filter air and water, and also protect the storehouse of plant or animal species that may form the basis of medicines, compounds or natural products of value to humans.

Protection against the spread of disease should more often be added to that list, they said.

"Emerging infectious diseases are on the rise in many ecosystems," said Andrew Blaustein, a co-author on this study, professor of zoology at OSU and leading researcher on the causes of amphibian declines.
"Protection of biodiversity may help reduce diseases," he said. "It's another strong argument for why diverse ecosystems are so important in general. And it's very clear that biodiversity is much easier to protect than it is to restore, once it's lost."

The fungus, B. dendrobatidis, can lead to death from cardiac arrest when it reaches high levels in its amphibian hosts. It is not always fatal at lower levels of infection, but is now causing problems around the world. One research team has called the impact of the chytrid fungus on amphibians "the most spectacular loss of vertebrate biodiversity due to disease in recorded history."

Amphibians face threats from multiple causes, including habitat destruction, pollution, increases in ultraviolet light due to ozone depletion, invasive species, and infectious disease.

The dilution effect can occur in plants and animals, but also in human diseases. In a different report published in Nature, researchers noted an increased risk of West Nile encephalitis in the U.S. in areas with low bird diversity. And in more diverse communities, the infection of humans by schistosomiasis -- which infects 200 million people worldwide -- can be reduced by 25-99 percent.

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Engineers use short ultrasound pulses to reach neurons through blood-brain barrier

Islamabad, Sep 23 (Newswire): Columbia Engineering researchers have developed a new technique to reach neurons through the blood-brain barrier (BBB) and deliver drugs safely and noninvasively. Up until now, scientists have thought that long ultrasound pulses, which can inflict collateral damage, were required.

But in this new study, the Columbia Engineering team show that extremely short pulses of ultrasound waves can open the blood-brain barrier -- with the added advantages of safety and uniform molecular delivery -- and that the molecule injected systemically could reach and highlight the targeted neurons noninvasively.

The study, led by Elisa Konofagou, associate professor of biomedical engineering and radiology, was published in the Proceedings of the National Academy of Sciences.

"This is a great step forward," says Konofagou. "Devastating diseases such as Alzheimer's and Parkinson's that affect millions of people are currently severely undertreated. We hope our new research will open new avenues in helping eradicate them."

Highly specific delivery of drugs to human organs is essential for the effective treatment of many diseases. But the brain presents a difficult problem: it has a unique vascular system -- the blood-brain barrier -- that acts as a closed door to prevent the entry of foreign molecules. While it protects the brain from potentially toxic substances, it also prevents the delivery of therapeutic drugs to the brain. Because many molecules cannot cross the BBB, available treatments for patients with neurological disorders have been severely limited. Konofagou and her team are focused on getting the door opened enough to safely reach those cells that need to be treated.

Konofagou and her team have designed a focused ultrasound method that can target only the area of the hippocampus that is affected in early Alzheimer's. In this study, they administered microbubbles to enhance the intended mechanical effect, and a high-field MRI to detect and map the area of BBB opening as well as quantify the permeability of the opened BBB. They also used fluorescence confocal microscopy to visualize the molecular diffusion and neuronal enhancement in 3-D to identify both highlighted neurons and their network.

More testing is planned with therapeutic drug treatments. Konofagou's team has shown that therapeutic molecules trigger downstream effects after diffusion through the blood-brain barrier, starting with the cell membrane and all the way through the nucleus. They also are unveiling the mechanism of the opening that involves stable oscillation or collapse of the bubble, with the former being the preferred mechanism as it is? completely controlled by the pressure and microbubble size.
The blood-brain barrier has been shown to recover within the range of three hours to three days depending on the aforementioned parameters used. Konofagou's group has also recently reported that transcranial human targeting of the hippocampus, caudate, and putamen in the human brain is feasible in both simulations and in vitro experiments, thus paving t

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