BreakThrough Digest Medical News |
| Pioneering research into rare neonatal diseases Posted: 12 Aug 2012 09:00 PM PDT Groundbreaking research into rare neonatal diseases, conducted by the University of Sheffield, is set to improve the treatment of babies who lack the stress hormone cortisol.
A European Union grant, awarded to the University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust with pharmaceutical Diurnal Ltd and partners, will assist the development of a novel neonatal formulation of hydrocortisone ? a steroid drug that is essential for the survival of babies who lack the hormone cortisol. Known as the stress hormone, cortisol is secreted from the adrenal gland in the body – without it infants cannot survive. Cortisol has a critical role in combating infections or other sources of physical stress such as extreme exercise or surgery. The most common cause of adrenal insufficiency in neonates is congenital adrenal hyperplasia (CAH). Approximately 1 in every 12,000 children is born with CAH which is a rare genetic disorder that blocks the adrenal glands’ ability to synthesise cortisol. Due to numerous ethical and practical challenges of testing medications, newborns, neonates and infants are often thought to be at a disadvantage when it comes to new medical treatment, because they have to be treated with drugs that were developed for adults. Professor Richard Ross from the University of Sheffield’s Medical School said: “Adrenal insufficiency is a serious condition resulting from a lack of stress hormone cortisol, and untreated patients will die from an adrenal crisis. “Currently there is no licensed preparation to treat neonates and infants with adrenal insufficiency, and parents have to use crushed adult tablets, which have associated risks of over- and under-treatment. Under-treatment can be potentially lethal, while over-treatment results in growth failure and obesity.” The European collaborative project Treatment of Adrenal Insufficiency in Neonates and Infants (TAIN) ? Development of Hydrocortisone Preparation for the Treatment of Adrenal Insufficiency in Neonates and Infants, began in December 2011 and involves European leaders in neonatology, paediatric pharmacology and clinical trial methodology, together with a number of small and medium enterprises. Professor Ross added: “The TAIN project will deliver the first licensed preparation specifically designed for parents to treat their babies with ease of administration, taste masking and appropriately tailored doses. “As physicians, we are increasingly aware that treatments given as early in life as possible can have an important impact on development and health later in life. TAIN aims to optimise treatment for babies with adrenal insufficiency, and will strengthen paediatric drug evaluation across Europe by building a network of units experienced in clinical research delivering appropriate formulations for neonates and infants.” TAIN coordinator, Martin Whitaker from the University of Sheffield, said: “The funding of the TAIN programme by the European Commission will, for the first time, allow the possibility to develop an effective paediatric medicine for the rare disease adrenal insufficiency. “The outcomes of TAIN will make a real and significant difference to the loves of young children suffering from this disease, who currently have to rely on unlicensed, sub-optimal medications. The TAIN project also includes a consortium to monitor all ethical aspects of the research, to ensure that the resulting product will be safe and efficacious for use in children from birth. ### Notes for Editors
The Faculty of Medicine, Dentistry and Health The University of Sheffield
With nearly 25,000 students from 125 countries, the University of Sheffield is one of the UK’s leading and largest universities. A member of the Russell Group, it has a reputation for world-class teaching and research excellence across a wide range of disciplines. The University of Sheffield has been named University of the Year in the Times Higher Education Awards for its exceptional performance in research, teaching, access and business performance. In addition, the University has won four Queen’s Anniversary Prizes (1998, 2000, 2002, 2007). These prestigious awards recognise outstanding contributions by universities and colleges to the United Kingdom’s intellectual, economic, cultural and social life. Sheffield also boasts five Nobel Prize winners among former staff and students and many of its alumni have gone on to hold positions of great responsibility and influence around the world. The University’s research partners and clients include Boeing, Rolls Royce, Unilever, Boots, AstraZeneca, GSK, ICI, Slazenger, and many more household names, as well as UK and overseas government agencies and charitable foundations. The University has well-established partnerships with a number of universities and major corporations, both in the UK and abroad. Its partnership with Leeds and York Universities in the White Rose Consortium has a combined research power greater than that of either Oxford or Cambridge Contact: Amy Pullan
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| New method may allow personalized clinical trial for cancer therapies Posted: 12 Aug 2012 09:00 PM PDT A new tool to observe cell behavior has revealed surprising clues about how cancer cells respond to therapy ? and may offer a way to further refine personalized cancer treatments. The approach, developed by investigators at Vanderbilt-Ingram Cancer Center, shows that erlotinib ? a targeted therapy that acts on a growth factor receptor mutated in some lung, brain and other cancers ? doesn’t simply kill tumor cells as was previously assumed. The drug also causes some tumor cells to go into a non-dividing (quiescent) state or to slow down their rate of division. This variability in cell response to the drug may be involved in cancer recurrence and drug resistance, the authors suggest.
The new tool, reported Aug. 12 in Nature Methods, may offer ways to improve personalized cancer therapy by predicting tumor response and testing combinations of targeted therapies in an individual patient’s tumor. In the personalized approach to cancer treatment, a patient’s tumor is analyzed for a set of mutations to which there are matching drugs that act on those mutations. This approach has worked rather well for many cancers that carry specific mutations, said senior author Vito Quaranta, M.D., professor of Cancer Biology. “The genetics is well understood, the clinical effect is understood and the chemistry behind the therapy is understood. But there is a missing piece,” said Quaranta. “Believe it or not, what is actually not understood is how cells respond to these drugs, what is actually happening.” The prevailing view has been that targeted therapies kill all the cells harboring a particular mutation. But even if the tumor is composed entirely of genetically identical cells ? which is unlikely ? a drug will not affect all cells the same way, Quaranta explained. “Some of these cells may die, some may just stop dividing and sit there (called quiescence), and some may keep dividing, but more slowly.” However, no current tests can provide an accurate, detailed picture of cell behavior needed to understand tumor response to drugs. So, the investigators, led by first author Darren Tyson, Ph.D., research assistant professor of Cancer Biology, combined powerful automated, time-lapse microscopy with analytical tools and software they developed. Using these techniques, they could capture the behavior of lung cancer cells every six to 10 minutes for up to 10 days. As they expected, the targeted therapy erlotinib killed some cells, while others became quiescent. They observed that the drug even affected genetically identical cells (cells that arose from the same parental cell) differently. “These cells are clearly genetically identical, as identical as they can possibly be because one cell just divided into two, but you get completely different responses: one dies and the other one doesn’t,” said Tyson. “This suggests that there are other things besides genetics that have to be taken into account.” What those other factors are remains unclear, but the investigators are conducting follow- up experiments to determine what might underlie this differential response. “And presumably, it is those (quiescent) cells that ultimately result in tumor recurrence,” said Tyson. Quaranta and colleagues hope to take the technology into small clinical trials to test whether it can predict a patient’s response to therapy. “We think that we might be able to forecast what the response is going to be,” Quaranta said. “We can take samples from the tumor, subject them to this assay, and since we’re looking at response over time, we will have a rate of response.” This could tell oncologists how long a patient’s tumor will respond to a given therapy before it recurs. Such information could also help determine which patients will require more aggressive treatment ? and Quaranta believes the assay will be able to test combinations of drugs on a patient’s tumor cells to find the right combination to induce a response. “We’re hoping that this assay ? or some implementation of this assay ? will eventually work like a personalized clinical trial,” Quaranta said. ### Graduate student Peter Frick and data analyst Shawn Garbett were co-authors on the paper. The research was supported by a grant from the National Institutes of Health/ National Cancer Institute Integrative Cancer Biology Program (CA113007). Contact: Melissa Stamm |
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