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Tysabri
Elan Sank To New Low For Year Friday
Trading Markets (press release) - Los Angeles,CA,USA
... two confirmed cases of a potentially deadly brain infection after the close Thursday, in multiple-sclerosis patients being treated with Tysabri. ...
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MS drug fear sends Elan shares crashing
Belfast Telegraph - United Kingdom
Yesterday Elan and Biogen insisted that Tysabri would not be pulled from the market as happened in 2005 when the companies voluntarily removed the treatment ...
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Brain disease scare sees Elan shares crash
Belfast Telegraph - United Kingdom
Drugs giant Elan has lost over half its share value on the Irish stockmarket in early trading on Saturday after its popular Tysabri multiple sclerosis drug ...
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ANALYSIS-Biogen sell-off deja vu all over again
Reuters - USA
O: Quote, Profile, Research) are racing for the exits amid renewed safety concerns over its multiple sclerosis drug Tysabri, but if history is any guide, ...
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Biogen, Elan Defend Multiple Sclerosis Drug Tysabri After Two ...
Trading Markets (press release) - Los Angeles,CA,USA
(NYSE: ELN | Quote | Chart | News | PowerRating) defended their multiple sclerosis drug Tysabri after disclosing two new cases of a potentially fatal side ...
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Life Sciences 25
Boston Globe - United States
Biogen Idec reported two new cases of a rare disease linked to the drug Tysabri; Bruker reported better-than-expected earnings. The Boston Globe/Bloomberg ...
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Stock market woes
Irish Times - Dublin,Ireland
... when the share price of pharmaceutical firm Elan fell by 46 per cent on Friday after it reported complications with its multiple sclerosis drug Tysabri. ...
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Biogen sell-off deja vu all over again
guardian.co.uk - UK
In 2005, Tysabri was withdrawn from the market after it was linked to three cases of PML, sending Biogen's shares plunging. But the drug was reintroduced in ...
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Makers of MS Drug Confirm Two Cases of Life-Threatening Brain Infection
Audio: Cecil Pickett, Ph.D., and Alfred Sandrock, M.D., Ph.D.
Biogen Idec
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Makers of MS Drug Confirm Two Cases of Life-Threatening Brain Infection |
| By Peggy Peck, Executive Editor, MedPage Today Published: August 01, 2008 Reviewed by Zalman S. Agus, MD; Emeritus Professor University of Pennsylvania School of Medicine. |
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| Audio: Cecil Pickett, Ph.D., and Alfred Sandrock, M.D., Ph.D. Biogen Idec |
Cecil B. Pickett, Ph.D., president of Biogen Idec, said in a conference call with analysts that the two PML cases are the first since the drug was reintroduced to the U.S. market in 2006.
He said an estimated 32,000 MS patients worldwide are receiving the drug. He said 13,900 of them have taken it for more than 12 months, and 6,600 have used it for more than 18 months.
The company said that more than 17,000 U.S. patients take the drug.
Biogen Idec and Elan developed the drug, and Dr. Pickett said the companies received confirmation of the first case on Wednesday and the second case was confirmed yesterday.
In both cases PML was confirmed in the presence of symptoms, MRI evaluation, and confirmed JC viral DNA in cerebrospinal fluid.
One patient was described as "stable, ambulatory, and at home," while the other was described as hospitalized, but clinically stable.
The drug was initially approved by the FDA in November 2004, but was withdrawn from the market in February 2005 after three patients developed PML. Two of those patients died.
The drug was reintroduced under a special restricted distribution plan that requires a registry for all patients as well as follow-up at three and six months after initial infusion and follow-up every six months thereafter.
Alfred Sandrock, M.D., Ph.D., senior vice president for neurology research and development at Biogen Idec, said the first patient had aggressive relapsing MS and was treatment naive when he began therapy in December 2006.
He developed a focal twitch and left-sided weakness after 17 months on natalizumab monotherapy, but had no cognitive symptoms.
Initial MRI was equivocal and initial CSF testing was negative, but despite the absence of JC viral DNA in the CSF, plasma exchange was initiated. The patient underwent five plasmapheresis treatments over the course of 10 days.
"A second CSF test confirmed the presence of JC virus DNA," Dr. Sandrock said. He said the patient was stable, at home, but the focal twitch and left-sided weakness remained.
The second patient was diagnosed with MS in 1992 and had a long history of therapeutic interventions, prior to initiation of natalizumab. This patient developed left-side hemiparesis over the course of two months.
Dr. Sandrock said tests confirmed JV viral DNA in this patient's CSF and the patient is scheduled to begin plasmapheresis treatment.
Find this article at:
http://www.medpagetoday.com/Neurology/MultipleSclerosis/tb/10385
http://www.printthis.clickability.com/pt/cpt?action=cpt&title=Makers+of+MS+Drug+Confirm+Two+Cases+of+Life-Threatening+Brain+Infection&expire=&urlID=30120261&fb=Y&url=http%3A%2F%2Fwww.medpagetoday.com%2FNeurology%2FMultipleSclerosis%2Ftb%2F10385&partnerID=259706
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Subject: How much side effect risk is ok?
Remember Tysabri, the multiple sclerosis drug that was pulled from the market just months after its approval in 2004, because it increased the risk of a viral brain brain disease called progressive multifocal leukoencephalopathy (PML)?
Tysabri was reintroduced in 2006, and early this year was also approved for treating severe cases of Crohn's disease.
About two weeks ago, I got a press release from Biogen Idec and Elan, the companies that jointly market the drug, notifying me of its two-year anniversary, and pointing out the fact that more than 43,000 patients have been treated with the drug, that almost 14,000 have been on it for a year or more, and that no adverse effects of PML had been noted. Just last week, though, all that changed when the companies reported two new cases of PML in patients using the drug (see New York Times coverage here - http://www.nytimes.com/aponline/business/AP-Biogen-Elan-Tysabri.html?ref=policy).
Many doctors and patients have said that the benefits of the drug in managing MS far outweigh the risk, and so far, it sounds like the drug won't necessarily be pulled. But it really got me thinking about how much risk is acceptable. As biologics and other kinds of new medicines, such as targeted therapies, become more prevalent, are the risks increasing?
This message was edited 1 time. Last update was at Aug/04/2008 11:55:18
http://www.the-scientist.com/community/posts/list/140.page
"It's a stunning accomplishment," Neil Cashman, professor of neurology at the University of British Columbia who was not involved in the study, told The Scientist. "That they take somebody at the end of their life with a chronic disease and can still reprogram the cells -- it's a slam dunk."
The researchers, led by Kevin Eggan at Harvard University, infected the diseased cells with genetically modified viruses coding for the four transgenes Klf4, OCT4, SOX2, and c-Myc, the same cocktail of genes used by one of two groups last November in the first reprogramming studies. The cells containing the mutation SOD-1, which is responsible for the familial form of ALS, were successfully reprogrammed (into iPS cells) and differentiated into motor neurons.
There are a couple of caveats to the findings, however. Firstly, the team did not show that the motor neurons developed the pathology of the disease. "The next major question is whether the ALS motor neurons are in any way different to those from non affected patients," Clive Svendsen, neurologist at University of Wisconsin, Madison, who was not involved in the study, wrote in an Email to The Scientist. The researchers are confident that in time the cells would show the marked deterioration associated with ALS, Eggan told reporters during a teleconference. In addition, the team found that some of the tumorigenic genes required for reprogramming were downregulated when they differentiated the cells into neurons, but some continued to be expressed. "This is worrisome," said Cashman. Using genetically altered cells that express tumorigenic genes is still too dangerous for patient application, said Eggan.
Perhaps the most important caveat to the study, however, was that it did not demonstrate the ability of the motor neurons to establish connections in vivo with muscle fibers and integrate into the nervous system. For now, the reprogrammed cells will be a boon to laboratory research, said Eggan. "Because those stem cells harbor the genes which ultimately led to the disease in the patient, if we could produce cell types that become sick, we can use them in the laboratory to understand aspects of disease -- we take the study of disease out of patients and put it in the Petri dish."
The cells may give researchers the opportunity to study the mechanisms that lead to the disease in the first place. "The mechanism is the key in our attempt to find a cure," Christopher Henderson, from Columbia University and coauthor on the study, said on the teleconference. "Using these degenerative iPS cells we can develop compounds that prevent that degeneration."
And, even though SOD-1 is responsible for less than 5% of all ALS cases, Henderson added, "Our real hope is that similar events are occurring in sporadic cases [of the disease] in which the trigger is different." Since the phenotypes of the genetic and the sporadic disease are so similar, he added, they believe there may be a similar mechanism at work.
Correction: The original version of this story incorrectly spelled the disease. A correction has been made, The Scientist regrets the error.
http://www.the-scientist.com/blog/display/54904/
The unassuming cells of a sea sponge may hold a clue to the origin of the nervous system, according to a paper published next Tuesday, August 5th, in Current Biology. The detection of proneural pathways in the ancient organism suggests that genes for neurogenesis evolved earlier than previously believed.
Researchers have widely believed that nerve cells evolved after the divergence of sponges, which lack organs and nervous systems, from the rest of the animal kingdom (bilaterians). But Bernard Degnan of the University of Queensland in Australia and colleagues detected the expression of two key components of neuronal differentiation in bilaterians, Notch-Delta signaling and basis helix loop helix (bHLH) genes, in the surface cells of the sea sponge Amphimedon queenslandica.
"Notch signaling is the most important pathway in neurogenesis," said Hugo Bellen, a neuroscientist at Baylor College of Medicine, who was not involved in the study. "It's surprising that it [developed] so early in evolution."
The team scanned the genome of Amphimedon, the first sponge to have its full genome sequenced, for gene homologs to bHLH and Notch signaling pathway genes. After identifying them in the genome, the team carried out in situ hybridizations to prove that the genes are expressed in the outer layer of cells of a late Amphimedon embryo.
Then in a functional study, the scientists injected Xenopus and Drosophila embryos with transcribed mRNAs from one of the Amphimedon homologs, AmqbHLH1. Neurogenin is the most important gene for neuron differentiation in Xenopus, a vertebrate, while Drosophila relies primarily on another proneural gene, atonal. Although each species has both genes, swapping the primary gene expressed, neurogenin for atonal and vice versa, results in minimal neuron growth. However, expression of AmqbHLH1 induced proneural activity in both species, mimicking the proneural gene of choice: neurogenin in Xenopus and atonal in Drosophila. It is "compelling evidence of the deep conservation of this system," wrote Degnan in an Email, indicating that the proneural pathways existed at the dawn of the Metazoa, some 50 million years earlier than previously thought.
Degnan describes the globular cells as a layer of sensory cells "akin to a disconnected nerve net." But Bellen said he hesitates to refer to them as sensory cells, as their function was not determined in the paper. "It'd be nice to know exactly what these cells do."
Degnan and his team are currently working to determine if the cells have sensory function, and their data suggest the cells are involved in sensing the environment, Degnan noted.
http://www.the-scientist.com/blog/display/54903/
The long and winding road
An author traverses intellectual intrigue and scientific rivalry to trace the conceptual evolution of the gene
By James Schwartz[Published 31st July 2008 08:44 PM GMT]
Simultaneously abstract and personal, the early study of heredity touched on age-old philosophical questions about free will and determinism, the relationship between parent and child, and the extent to which human beings can be reduced to the sum of their parts. Fueled by their concern with these elemental themes, the geneticists of the 19th and early 20th centuries were a particularly passionate group, pathologically competitive in some instances and utterly selfless in others. They were prone to intense loyalties as well as overwhelming hatreds, singularly idealistic and ruthlessly pragmatic.
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The story of the gene begins with Charles Darwin's arcane and deeply flawed "provisional hypothesis of Pangenesis," which reflected his conversion to another highly problematic theory, that of Lamarckian inheritance. Despite its many problems, Darwin's Pangenesis theory posited the existence of microscopic hereditary particles, a construct that would play a crucial role in the development of modern ideas about the gene. No sooner had Darwin proposed his model than his cousin, Francis Galton, commandeered it to support a theory of inherited intelligence that was itself based on a host of erroneous assumptions and ad hoc arguments. Nonetheless, Galton's hereditary theory was much closer to the truth than that of his far more emotionally balanced, reasonable, and steadfast cousin. Meanwhile, unbeknownst to Darwin and Galton, Gregor Mendel had managed to divine the essence of modern genetics in 1865, working alone in a monastery in Austrian Silesia.
The Dutch botanist Hugo de Vries also tried to enlist Darwin's theory of Pangenesis in the service of his own Mutation Theory, hoping to displace Darwin as the central figure in modern biology. In the course of his work, De Vries stumbled on Mendelism but failed to recognize the importance of Mendel's work and instead spent the remainder of his life devaluing Mendel's achievement and promoting his own erroneous theory in its place.
The cause of Mendelism was then taken up by English zoologist, William Bateson, who was driven to a feverish pitch in its defense by his desire to expose the folly of his once best friend Frank Weldon, who stubbornly refused to acknowledge that inheritance might be governed by concrete structural elements that were passed from parent to offspring. Bateson, who felt Weldon had betrayed the pursuit of truth, later himself refused to accept the idea that the genes were arranged on chromosomes.
The post-1900 development of classical genetics took place largely in Thomas Hunt Morgan's Columbia University laboratory, where between 1912 and 1915 his three graduate students - Alfred Sturtevant, Calvin Bridges, and Hermann Muller - integrated Mendelism and the chromosome theory to form the basis for modern genetics. Ironically, Morgan stood opposed to all three of the major developments in contemporary biology - Darwinism, the chromosome theory, and Mendelism - when he began to study the common fruit fly in 1909. The following year, despite his doubts about both Mendel's factors and the importance of the chromosomes, Morgan discovered the first definitive proof that a Mendelian factor was associated with a particular chromosome - the sex-linked X chromosome.
But Morgan's continued equivocation about Darwinism and the implications of the chromosome theory led to a falling out with Muller, who had already begun to see his way toward a new synthesis of Mendel and Darwin. Despite a well-known account written by Sturtevant late in his life depicting Morgan's laboratory as a kind of scientific utopia, the atmosphere was fraught with rivalries. While Morgan and Sturtevant partially succeeded in tainting Muller's reputation, Muller went on to develop the modern theory of the gene, which served as the foundation for modern molecular biology. In fact, without any structural knowledge of DNA, Muller laid out the conceptual basis for the current effort to identify the genes involved in complex human traits.
The path leading to the development of the modern gene concept was a circuitous one, at least in part because of the prejudices and idiosyncrasies of the scientists who undertook the journey. Danger lurked in the very passions that made scientific progress possible. This is truer than ever today, as scientists attempt to dissect the genetic basis of human disease and even complex psychological traits. Nevertheless, in the case of the gene, clarity was eventually achieved. One thing that helps is the system itself - no matter what prejudices a scientist brings to his work, each new idea, in order to survive, must be tested in controlled experiments and must hold up under the scrutiny of other scientists. At the same time, this system and the scientific freedoms it rests on cannot be taken for granted. At a time when we are increasingly in control of our destiny, genetic and otherwise, it is worth reflecting on the nature of scientific inquiry and the requirements for its long-term health.
James Schwartz is the author of In pursuit of the gene: From Darwin to DNA. He is an independent scholar and science writer who lives in Brookline, Massachusetts with his wife and two sons.
James Schwartz
mail@the-scientist.com
http://www.the-scientist.com/news/display/54906/
Calif. animal scientists attacked
Posted by Bob Grant
[Entry posted at 4th August 2008 03:44 PM GMT]
A house and car belonging to two University of California, Santa Cruz researchers were firebombed in the wee hours of Saturday (Aug 2) morning. The attacks occurred after anti-animal research pamphlets listing the names and personal information of several UCSC researchers were discovered in a Santa Cruz coffee shop last week.
David Feldheim, who studies mammalian brain development at UCSC, and his family were home Saturday morning when fire engulfed their front porch and door. Feldheim and his family - including two small children - escaped out a second story window using a fire ladder, Santa Cruz police told the Santa Cruz Sentinel.
Feldheim studies the role of the Eph family of receptor tyrosine kinases and their ligands, the ephrins, in the development of the mouse visual system. According to his lab Web site, Feldheim uses "expression analysis, in vitro assays, viral introduction of genes into living mouse brains, and gene-knock out experiments," to elucidate how mouse brains organize neural connections associated with vision. Feldheim was one of the scientists listed on the pamphlets found last week. Police told the Sentinel that the firebombing was being treated as an attempted homicide because Feldheim and his family were home at the time of the attack.
Around the same time that Feldheim's house burned, another UCSC scientist's Volvo was lit afire in a driveway on the university's campus. Neither police nor UCSC officials revealed the researcher's field of study or name, but they did say that it was not listed on the pamphlet in which Feldheim's name and information appeared.
According to the Sentinel, Santa Cruz police are considering the incidents acts of domestic terrorism and have turned the case over to federal investigators. "It's unconscionable that any reasonable person would consider this an acceptable tactic to get their point across," Santa Cruz Police Chief Howard Skerry said in a statement to the Sentinel. "We are working hard with the other agencies and committing all available resources to follow all possible leads. We urge anyone with information to come forward."
A news release from the university on Saturday condemning the attacks called them "acts of anti-science violence."
http://www.the-scientist.com/blog/display/54910/
posted by Bill at 3:43 PM
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