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Interferon-free therapy for hep C


Origins of life


Life begins closer to home


Maria Burke


‘I think it is a breakthrough because it suggests


The building blocks for making RNA – thought to play a pivotal role in the origins of life on Earth – could have been derived from one simple molecule in the atmosphere, UK scientists report. Their findings support the theory that the genetic material essential for life originated from the planet’s atmosphere and minerals on its surface rather than being brought to Earth from outer space. The team from the


that a simple atmospheric compound can be converted


to sugars’ John Sutherland


Emma Dorey


The race by big pharma to develop a better and more convenient treatment for patients infected with hepatitis C virus (HCV) has a new contender.


An estimated 170m people are infected with HCV and up to 4m acquire the infection each year. But treatment is lacking; patients with the most prevalent HCV infection (genotype-1) are typically given a combination of interferon and ribavirin – a regimen that is successful in less than half of patients, involves weekly injections for 48 weeks, and causes adverse events such as anaemia, depression and flu-like symptoms. Although cure rates have risen to around 70% with the addition of newer protease inhibitors – such as Vertex’s Telaprevir and Schering-Plough’s Boceprevir – these treatments still require interferon. However, pharma major Abbott is developing an interferon-free cocktail that has shown promise in a Phase 2b trial in which 99% of untreated patients given the regimen for just 12 weeks showed no sign of the virus. HCV was also eliminated in 93% of patients


who had previously failed to respond to other therapies. The treatment consists of three direct-acting


antivirals – ABT-450 (a protease inhibitor), ABT-267 (a polymerase inhibitor) and ABT-267 (an NS5A inhibitor) – taken with ribavirin, a nucleoside analogue with antiviral activity. It is also delivered orally as tablets and pills. ‘Abbott’s interferon-free oral combination


for HCV treatment is stunning,’ says Debbie Green, president of the Greenview Hepatitis C Fund. ‘For years all HCV treatment has been based on interferon, which causes side effects so severe that patients drop out of treatment. Many HCV patients have been putting off treatment because of this drug and have been holding out for a safer, shorter and more effective treatment.’ ‘Getting rid of interferon is perhaps the single biggest advance that we are likely to see,’ says Charles Gore, chief executive of the Hepatitis C Trust. ‘It will make many more people willing to do treatment.’ Full results from Abbott’s study will be


presented this month at the Annual Meeting of the American Association for the Study of Liver Disease in Boston, US.


Medical Research Council’s Laboratory of Molecular Biology in Cambridge claims to have shown that the sugar building blocks for the synthesis of RNA – glycolaldehyde and glyceraldehyde – can be formed from hydrogen cyanide using ultraviolet light and a copper salt as catalyst (Nature Chem., 2012, 4, 895). ‘I think it is a


breakthrough because it suggests that a simple atmospheric compound can be converted to sugars,’ says John Sutherland, one of the paper co-authors. ‘It was shown 50-odd years ago that the purine nucleobase adenine is also a product of HCN, so HCN – normally thought of as a poison – might be the source of the sugars and the nucleobases in RNA. Showing that RNA is ultimately a product of phosphate and HCN makes the origin of life based around RNA seem even more plausible.’ The metals and compounds involved in the


production of the building blocks of life could have come from meteorites that collided with Earth billions of years ago, he adds. The paper opens the door to different mechanistic pathways accounting for the prebiotic generation of sugars, says David Cantillo at the University of Extremadura, Spain. While this scenario is plausible, he adds, it should also be taken with caution. ‘I would rather be biased to conjecture, as the paper suggests at the end, that other more abundant minerals in a primeval Earth could have catalysed the process – if ultimately proven, especially iron. This would also represent a link to other theories on the origin of life, such as the Fe-Ni scenario hypothesised some time ago.’


Chemistry&Industry • November 2012 15


Russell Kightley/Science Photo Library


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