Monday, August 04, 2008

How much side effect risk is ok? - The Scientist Community - debate. relate. collaborate.

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. ...
See all stories on this topic




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 ...
See all stories on this topic



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 ...
See all stories on this topic



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, ...
See all stories on this topic



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 ...
See all stories on this topic



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 ...
See all stories on this topic



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. ...
See all stories on this topic



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In 2005, Tysabri was withdrawn from the market after it was linked to three cases of PML, sending Biogen's shares plunging.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 ...
See all stories on this topic





Makers of MS Drug Confirm Two Cases of Life-Threatening Brain Infection
Audio: C
ecil Pickett, Ph.D., and Alfred Sandrock, M.D., Ph.D.
Biogen Idec


MedPage Today
Powered by





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.
Audio: Cecil Pickett, Ph.D., and Alfred Sandrock, M.D., Ph.D.
Biogen Idec

CAMBRIDGE, Mass., Aug. 1 -- Two multiple sclerosis patients -- both in Europe -- have developed progressive multifocal leukoencephalopathy (PML) as a result of treatment with natalizumab (Tysabri), according to the makers of the drug.

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.


Additional Multiple Sclerosis Coverage




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



Sign Up to Be an MS Activist

Read the MS Activist Blog

Chapter Contacts for State Issues

Issue Briefs and Background

National MS Society Homepage

Federal Focus


10 Volunteers Selected for PRMRP Panels

This year, thanks to your help and activism, multiple sclerosis (MS) has been named as a topic area eligible for research funding through the Peer Reviewed Medical Research Program (PRMRP). This was a historic success as it was the first time MS has been recognized under this program.

The PRMRP is administered by the Department of Defense (DoD) as part of the Congressionally Directed Medical Research Programs (CDMRP), but the research areas listed in the PRMRP compete with other research areas as directed by Congress. The PRMRP has a research budget of $50 million and the research areas eligible under this program must compete in order to receive funding.

In May, the DoD invited individuals with MS or who have a family member living with MS, to join scientists on a peer review panel to select applications to receive funding for MS research. This group will review and select proposals based on scientific merit and programmatic comparisons to other proposals in that category.

The DoD selected 10 volunteers to serve on the MS-related PRMRP panels in September. This number surpassed our expectations and indicates the strong need for MS research funding. These volunteers, representing a good geographic distribution, have a unique opportunity to help guide the scientific review process with their perspectives and insights related to their experience with MS.

The DoD received a total of 142 applications for MS funding. This shows that there is a tremendous need for this program and magnifies the value of your work over the past two years to secure MS recognition within it.

Click here to learn more about the PRMRP.


It's Time to Secure $15 Million for MS Research

63 members of the House of Representatives and 27 Senators have signed on in support of a $15 million appropriation for MS research in the Congressionally Directed Medical Research Programs (CDMRP), a program funded annually by the Defense Appropriations Act. Last year, for the first time ever, MS became eligible to compete for research funding under the PRMRP. It is now time to build upon last year's success to secure a specific funding program for MS under the CDMRP.

It is important that your federal legislators hear from people who support this request and this cause. Being an election year, legislators will focus specifically on the top issues that impact their constituents more than any other time during the legislative cycle. Congress is on recess for most of August and at home in their respective states and districts. Take advantage of this great opportunity to meet with your legislators and make sure they understand the need for MS research funding in the CDMRP program.

Now is the time to talk to your Representative and Senators about MS research in the CDMRP because the Appropriations Committee in each chamber is currently preparing the Defense Appropriations Act. The CDMRP is funded annually through this appropriations bill.

Click here for more information and talking points.

Take Action Today

  • Call your Representative and/or both Senators to schedule a district meeting during the August recess. Visit www.house.gov and www.senate.gov for your legislator's contact information.
  • Attend a community or town hall meeting to bring up this issue. Contact the district office for a schedule.

Many U.S. veterans have stories and symptoms of multiple sclerosis. The DoD has an obligation to fund research for diseases related to military service. This research would benefit our veterans, and would help move us closer to a world free of MS.

You have the chance to participate in and influence an issue that will be a legislative focal point, since the Defense Appropriations bill is the only bill expected to pass through Congress and be signed by the president this fiscal year. The rest of the federal government will likely be operating under a Continuing Resolution (CR) until the next Congress.

This is the time to make a difference. Act now to demonstrate the great need for further MS research opportunities for our nation's veterans and general population.


Thank you for being a MS activist.

Join the movement at www.nationalMSsociety.org/advocacy.

To keep future MS activism messages out of your junk folder, add the following address to your contacts or safe sender list: MSActionNetwork@nmss.org


If you no longer wish to receive e-mail from us, please click here.






http://www.the-scientist.com/community/posts/list/140.page






The image “http://images.the-scientist.com/graphics/interface/toptoolbar/logo.gif” cannot be displayed, because it contains errors.

Diseased cells made pluripotent
[Entry posted at 31st July 2008 07:00 PM GMT]
Researchers have for the first time been able to generate a pluripotent stem cell line from the cells of a patient with a genetic disease, according to a study appearing tomorrow (August 1) in Science. The scientists successfully reprogrammed skin cells from an 82-year-old patient with Amyotrophic Lateral Sclerosis (ALS) into healthy motor neurons.

"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 image “http://images.the-scientist.com/graphics/interface/toptoolbar/logo.gif” cannot be displayed, because it contains errors.
Nerves of sponge?
[Entry posted at 31st July 2008 05:00 PM GMT]

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 image “http://images.the-scientist.com/graphics/interface/toptoolbar/logo.gif” cannot be displayed, because it contains errors.

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.

For these reasons I chose to take a novelistic approach to the history of genetics, which was possible because many of the players who made the key discoveries were skilled, prolific letter writers. From these letters and other primary source material, it was possible to trace the idea of the gene as it left one consciousness and entered another. Sometimes ideas were passed down from one scientist to another just as the originator intended. Other times, terrible confusion in one person's mind resulted in a brilliant illumination in the next. Still other times, researchers found the correct path by accident after setting off on the wrong one or, conversely, began with a brilliant flash of insight and proceeded to wander deep into the wilderness. In the end, I found that the history of the evolving concept of the gene coalesced into a coherent narrative, a complex scientific and human drama unfolding over more than a hundred years.

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/





The image “http://images.the-scientist.com/graphics/interface/toptoolbar/logo.gif” cannot be displayed, because it contains errors.
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/

0 Comments:

Post a Comment

Links to this post:

Create a Link

<< Home