This Week on CENtral Science: Papal Chemistry, Neuroscience of Magic, Pi Day, and more
Mar15

This Week on CENtral Science: Papal Chemistry, Neuroscience of Magic, Pi Day, and more

Tweet of the Week: Pope Francis, Jorge Mario Bergoglio, came late to the priesthood after studying chemistry. My question is: What turned him off to chemistry?— Gary Garchar (@ggarchar) March 14, 2013 I've had a blast as CENtral Science overlord. Like other despots before me, I have a hard time letting go of power. So now that Rachel's back, we'll be switching off on these roundup posts each month. To the network: Fine Line: Waldorf Time Again Grand CENtral: Top 10 Shoutouts to Pope Francis and Chemistry – Storify Just Another Electron Pusher: A Troubling Shift in Tradition Newscripts: Alakazam! The Neuroscience of Magic and Amusing News Aliquots and There & Back Again: A Cyclotron’s Tale Terra Sigillata: How Would You Explain pH to First-Graders? and Are Popes and Chemistry Immiscible? The Safety Zone: UK thallium and arsenic poisoning case neither accident nor suicide attempt and Explosives case continued for former UC Davis chemist David Snyder and Friday chemical safety round up *not up as of 4:20PM Eastern, but this link will work when it posts. The Watch Glass: “Inert” Xenon Reacts with Fluorine and Nanotubes' Electronic Properties and Bohemian retorts and Calculate pi with frozen hot dogs and Albert Ghiorso: Element...

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A Dynamic Neuron & His Dynamic Poster At #SfN12
Oct19

A Dynamic Neuron & His Dynamic Poster At #SfN12

Ned The Neuron If you attended the Society for Neuroscience’s annual meeting earlier this week (SfN 2012) in New Orleans, you might have passed by a blonde woman carrying a fuzzy blue stuffed neuron. Lest you think you had one too many drinks on Bourbon Street, I’m here to tell you this was no hallucination. The neuron’s name is Ned. He’s an adventurous sort with a bunch of fun-loving friends—Stella the stellate nerve cell and Bernard the bipolar retinal cell, to name a few. At the moment, Ned works in the motor cortex of the brain, helping humans put one foot in front of the other to traverse the great outdoors. The blonde carrying Ned is Erica Warp. Once a Ph.D. candidate at the University of California, Berkeley, studying spinal-cord development in zebrafish, Warp is Ned’s creator (and biggest fan). She dreamed him up during grad school, and when it came time to chart her future, she says the decision came down to “postdoc or Ned.” She chose the little blue guy. Along with developer Jessica Voytek, Warp has created an educational story platform around Ned: It includes a storybook overlaid with audio and music as well as interactive diagrams and mini-games. Voytek and Warp came to New Orleans to present a poster about their efforts to bring Ned’s story to life and to promote their iPad app, “The Adventures of Ned the Neuron.” (Android users, your app is coming soon.) “Neuroscience is a great gateway science for kids,” Warp says. “It’s cool. It’s something they can experience directly, through vision, touch, and other sensations.” But it’s also a subject that students typically don’t encounter until college, she adds. And that’s a shame. That’s because it’s a science that’s accelerating—a true frontier. There’s so much neuroscientists are now finding out about the brain, and there’s still so much they don’t know, Warp says. Kids should experience this vibrant field earlier, she contends. “Even if they don’t end up going into science later in life, we want them to have a positive association with it.” Voytek and Warp worked hard to get “The Adventures of Ned the Neuron” ready to launch at this year’s SfN meeting (having just established their company, Kizoom, in February). They managed to meet their deadline, although Warp says they are still doing some kid-testing and are making revisions to the app on the basis of feedback. Warp is hopeful that this initial story about Ned will be just the first in a series of adventures for Ned. If successful, she could see Kizoom adding stories to the app in which Ned explores other brain functions...

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Neuroscience Outtakes Part 2: Vanderbilt’s Jeff Conn on the Role of Academic Labs
Mar21

Neuroscience Outtakes Part 2: Vanderbilt’s Jeff Conn on the Role of Academic Labs

On Monday, we highlighted outtakes from our interview with Michael Ehlers, Pfizer’s CSO for neuroscience research, for our story on the state of neuroscience R&D. Today, we wanted to offer a view from academia: Jeff Conn is head of the Vanderbilt Center for Neuroscience Drug Discovery, which in the past several years has generated a number of CNS drug candidates. While Ehler is focused on the growing body of genetic information that could pave the way for new neuroscience targets, Conn’s lab is taking a somewhat different approach. By scouring the literature for evidence--in humans--of a molecule or target's activity, the lab then sinks substantial resources into understanding the basic biology driving that activity and designing molecules to exploit it. In depression, for example, R&D has been stalled by a lack of new targets. But Conn’s lab is intrigued by studies showing that ketamine, an animal tranquilizer (and club drug), swiftly and effectively reduces the symptoms of major depressive disorder. “When I talk to scientists at Vanderbilt, its an approach they’re using for their most refractory patients,” Conn says. A laundry list of side effects makes wider use of ketamine improbable. As such, Conn’s lab is looking at ways to design molecules that produce the same kind of results on depression without the adverse effects. Conn, a former Merck researcher, also discussed ways that discovery efforts inside academia can build a scientific case for CNS programs that pharma might otherwise overlook. Vanderbilt scientists spend “twice as much effort in basic science than for the drug discovery itself, and to me, that’s absolutely critical,” Conn says. When the team finds that molecules have different profiles in vitro, they spend a lot of time trying to understand how that will translate into adverse effects in vivo. “In pharma, you have to stay on such a narrow, direct path, that you have to ignore all that,” Conn says. In the academic lab, researchers take a longer, more methodical approach that entails optimizing many different molecules, then putting those in animals to understand what properties a final drug candidate needs to have. That approach has enabled Vanderbilt scientists to tackle drug targets that have tripped up industry. “mGluR5 is a good example where, early on, we started seeing different properties of molecules in vitro,” he says. “Instead of putting blinders on and moving forward or ignoring it,” an avenue industry scientists are often forced to take, “we deliberately put a lot of effort into optimizing those properties.” As a result, the Vanderbilt group and its collaborator, J&J, recently moved forward what Conn calls “very safe” schizophrenia drug candidates targeting mGlur5. “I don’t think...

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Wither Neuroscience R&D? Pfizer’s Ehlers Doesn’t Think So
Mar19

Wither Neuroscience R&D? Pfizer’s Ehlers Doesn’t Think So

In this week’s issue, I look at the perceived exodus by pharma companies from neuroscience R&D. Between AstraZeneca’s recent cutbacks, the closure of Novartis’ neuroscience research facility in Basel, and earlier moves by GSK and Merck, industry watchers are understandably worried that the neuroscience pipeline will dry up. One person who isn’t worried is Michael Ehlers, Pfizer’s chief scientific officer for neuroscience research. Ehlers came to Pfizer a year and a half ago from Duke, with the explicit mission to revamp how the company finds and develops drugs for brain diseases. The scientist is convinced that the field is ripe for new and better drugs, and that by staying in the game, Pfizer will be in a good position to capitalize on what he believes will be a healthy flow of new discoveries. Many drug companies argue that the risk in neuroscience simply doesn’t justify the investment. The overarching sentiment is that the brain is still a black box: good targets are few and far between; clinical trials are long and unpredictable; regulatory approval is tough; and generic competition is plentiful. For many big pharma firms, the math just doesn’t add up. “I personally don’t find that calculus to give you the total picture,” Ehlers says. Shifting resources away from neuroscience to focus on areas like oncology, where the environment looks favorable—clear clinical trial endpoints, the opportunity for fast-track approval, an easier chance for reimbursement from payors—only makes sense in the short term, Ehlers says. But that thinking “is short sighted as to where the fundamental state of biology is in neuroscience,” he says. Why is Ehlers so encouraged about a field that so many are walking away from? He believes that neuroscience is poised to benefit from the kind of genetic links that generated so many targets—and eventually so many targeted-drugs—in oncology. “There is going to be kind of a revolution in the next five years—it’s not going to be tomorrow…but you have to think about that inflection of opportunity over the five-to-ten year time horizon.” To take advantage of each new genetic clue, Ehlers has revamped Pfizer’s approach to neuroscience R&D. As this week’s story explains: In the past, big pharma often gave its scientists a mandate to work in areas such as Alzheimer’s or schizophrenia, regardless of tractable drug targets. Now at Pfizer, Ehlers says, his team is “indication agnostic.” Any program that Pfizer undertakes must have a critical mass of biological knowledge—for example, human genetics, human phenotyping, and evidence of dysfunctional neurocircuits—to convince Ehlers it’s worth pursuing. “We start there,” he says. “That hasn’t always been the case.” Moreover, Pfizer no longer relies on mouse...

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AstraZeneca to Shed 2,200 R&D Jobs
Feb02

AstraZeneca to Shed 2,200 R&D Jobs

AstraZeneca wielded a heavy ax to its workforce today as it prepares for tougher times ahead. The British-Swedish drugmaker is chopping 7,300 jobs, including 2,200 R&D positions, in hopes of achieving $1.6 billion in annual cost savings by 2014. This is the third round of major cutbacks at AstraZeneca. In 2010, the company announced plans to slash 8,000 jobs over four years, a move that added to the elimination of 15,000 jobs between 2007 and 2009. This specific round girds against an onslaught of generic competition for key products and accounts for several disappointments in the company's late-stage pipeline. In the coming months, the company will lose patent protection in various markets for the anti-psychotic Seroquel IR, the anti-cholesterol drug Crestor, and the blood thinner Atacand. Meanwhile, AstraZeneca’s late-stage pipeline has faltered. The recent setbacks (adding to earlier ones) include ending development of the PARP inhibitor olaparib, which prompted it to take a $285 million charge; a failed Phase III trial for the antidepressant TC-5214; and a thumbs down from FDA last month for dapagliflozin, a Type II diabetes drug being developed with Bristol-Myers Squibb. R&D has taken a heavy hit in each round of cuts. During the Q&A session following AstraZeneca’s earnings presentation, one analyst said his back of the envelope calculations suggest the company will have shed 7,600 R&D jobs between 2006 and 2014. Based on comments by AstraZeneca’s R&D chief Martin Mackay, small molecule research has born the brunt of those cuts. He noted that headcount in biologics research has grown, and pointed out that biologics now account for 40% of the company’s early-stage pipeline (candidates in studies earlier than Phase II), up from 15-20% in recent years. The latest R&D revamp will be primarily focused on AstraZeneca’s neuroscience activities, where the risk of investment is seen as particularly high. “It’s a really tough area,” Mackay said.  “The industry hasn’t produced enough and we haven’t produced enough.” The challenge was highlighted in November, when TC-5214, an anti-depressant being developed by Targacept and AstraZeneca, failed to show benefit in a Phase III trial. The bad news came as a surprise, as TC-5214 had demonstrated strong efficacy in smaller trials. Three other Phase III trials are underway, but analysts are skeptical that the program can be salvaged. “Prospects appear grim,” Leerink Swann analyst Joshua Schimmer said in a note last month. AstraZeneca is creating a small team of 40 to 50 scientists that will work with external partners in academia and industry to discover and develop neuroscience drugs. The adoption of this new strategy means that the company’s Montreal R&D facility will be shuttered, and it will end R&D at its Södertälje site in Sweden....

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