HUNTINGTON’S DISEASE IS brutal in its simplicity. The disorder, which slowly bulldozes your ability to control your body, starts with just a single mutation, in the gene for huntingtin protein. That tweak tacks an unwelcome glob of glutamines—extra amino acids—onto the protein, turning it into a destroyer that attacks neurons.

Huntington’s simplicity is exciting, because theoretically, it means you could treat it with a single drug targeted at that errant protein. But in the 24 years since scientists discovered it the gene for huntingtin, the search for suitable drugs has come up empty. This century’s riches of genetic and chemical data seem like it should have sped up research, but so far, the drug pipeline is more faucet than fire hydrant.

Part of the problem is simply that drug design is hard. But many researchers point to the systems of paywalls and patents that lock up data, slowing the flow of information. So a nonprofit called the Structural Genomics Consortium is countering with a strategy of extreme openness. They’re partnering with nine pharmaceutical companies and labs at six universities, including Oxford, the University of Toronto, and UNC Chapel Hill. They’re pledging to share everything with each other—drug wish lists, results in open access journals, and experimental samples—hoping to speed up the long, expensive drug design process for tough diseases like Huntington’s.

Rachel Harding, a postdoc at the University of Toronto arm of the collaboration, joined up to study the Huntington’s protein after she finished her PhD at Oxford. In a recent round of experiments, her lab grew insect cells in stacks of lab flasks fed with pink media. After slipping the cells a DNA vector that directed them to produce huntingtin, Rachel purified and stabilized the protein—and once it hangs out in a deep freezer for a while, she’ll map it with an electron microscope at Oxford.

Harding’s approach deviates from the norm in one major way: She doesn’t wait to publish a paper before sharing her results. After each of her experiments, “we’ll just put that into the public domain so that more people can use our stuff for free,” she says: protocols, the genetic sequences that worked for making proteins, experimental data. She’d even like to share protein samples with interested researchers, as she’s offered on Twitter. All this work is to create a map of huntingtin, “how all the atoms are connected to each other in three-dimensional space,” Harding says, including potential binding sites for drugs.


The next step is to ping that protein structure with thousands of molecules–chemical probes–to see if any bind in a helpful way. That’s what Kilian Huber, a medicinal chemistry researcher at Oxford University’s arm of the Structural Genomics Consortium, spends his days working on. Given a certain protein, he develops a way to measure its activity in cells, and then tests it against chemicals from pharmaceutical companies’ compound libraries, full of thousands of potential drug molecules.

If they score a hit, Huber and his consortium collaborators have pledged not to patent any of these chemicals. To the contrary, they want to share any chemical probe that works so it can quickly get more replication and testing. Many times, at other researchers’ requests, he has “put these compounds in an envelope, and sent them over,” he says. Recipient researchers generally cover shipping costs, and the organization as a whole has shipped off more than 10,000 samples since it started in 2004.

Under the umbrella of the SGC, about 200 scientists like Kilian and Rachel have agreed to never file any patents, and to publish only open access papers. CEO Aled Edwards beams when he talks about the group’s “metastatic openness.” Asking researchers to agree to share their work hasn’t been a problem. “There’s a willingness to be open,” he says, “you just have to show the way.”


Source: WIRED

31 Condivisioni