Saturday, February 11, 2012

Site Search

Archive for the ‘Press Releases’ Category

Ovarian Cancer Analysis Points to Common Gene Mutation, Research Says

Genetic mutations frequently found in the most common form of ovarian cancer were catalogued by U.S. scientists, paving the way for a more effective treatment of the disease.

The detailed genetic map already helped scientists identify existing drugs with the potential for treating the mutations found in ovarian cancer tumors and also identified mutations that could respond to new drugs.

The study, published Wednesday in the journal Nature, will contribute to a more personalized approach to cancer medicine because doctors will be able to treat patients according to the genetic mutations that drive the growth and spread of their tumors.

Scientists hope that the Cancer Genome Atlas project findings will allow them to understand how some genes cause cancer and develop drugs that control them.

Francis Collins — the director of the U.S. National Institutes of Health, in Bethesda, Md., which funded the research — said that “this landmark study is producing impressive insights into the biology of this type of cancer. It will significantly empower the cancer research community to make additional discoveries that will help us treat women with this deadly disease.”

In the study, scientists analyzed 316 ovarian tumors and found that the gene TP53 was present in 96 percent of the cancers. The study also found 108 genes linked to poor survival and 85 genes associated with better survival.

Ovarian Cancer is the fourth most common cause of female cancer deaths in the U.S. and kills nearly 14,000 women in the country each year.

Source: http://www.foxnews.com/health/2011/06/30/ovarian-cancer-analysis-points-to-common-gene-mutation-research-says/

The Second Disease To Ever Be Globally Eradicated: Rinderpest

One of the greatest scourges of human history is no more. For only the second time, modern public health practices have managed to eradicate a pandemic illness of global reach. The first was smallpox. Now what? AIDS? TB? No. Today, the world’s cattle are safe from rinderpest.

If you’ve never heard of rinderpest, it’s likely because you live in America, where thanks to the quarantine of distance and history the disease never established itself. But in the old world, cattle have kept company with humans for some 8,000 years, often in settings of extraordinary intimacy. Farm families throughout Europe lived in crofts, homes that doubled as stables; pastorlists like the Nuer people of Sudan, who drink not only cows’ milk but their blood as well, rely on cattle to supply nearly all their needs.

Through the many generations of coexistence, humans and their domesticated herds have shared their illnesses; smallpox, the only other disease eradicated by modern public health practices, likely began among cattle (the first smallpox vaccines were made by scraping matter from lesions on cows). In rinderpest, we humans returned the favor–scientists now think that the disease, a relative of measles, evolved from the human pathogen as recently as a thousand years ago.

Although no human ever fell ill from rinderpest, its toll on our species has been considerable. With mortality rates among afflicted herds approaching 90 percent, rinderpest outbreaks quickly starved populations of cattle-dependent farmers. In East Africa, its introduction had much the same effect as human diseases did in the New World in the wake of first European contact, laying waste to entire societies and rendering them defenseless in the face of colonialism. It has been blamed for the stagnation of agricultural economies and the rise and fall of empires. Though the last case was seen in 2001, farmers can now rest easy knowing the disease is fully contained. The benefits of rinderpest-free herds to agrarian economies will only grow with time.

Rinderpest’s eradication depended on recent innovations in medical practice. It took a combination of technical advances, including a new form of vaccine that doesn’t need to be refrigerated; and culturally-sensitive public health protocols, relying on local veterinary assistants rather than pith-helmeted foreign specialists to manage the disease in its far-flung pastures. Its eradication is evidence of one of the curious insights of modern public health: that while disease is global, medicine often takes a village.

Source: http://www.fastcompany.com/1764227/the-eradication-of-rinderpest

Genentech to Appeal to F.D.A. for Breast Cancer Drug

Genentech this week will step up its efforts to keep the drug Avastin available as a treatment for breast cancer, urging the Food and Drug Administration to give it one more chance to prove the medicine works.

At a hearing on Tuesday and Wednesday in suburban Washington, Genentech will ask the F.D.A. to reconsider its proposal last December to revoke the approval of Avastin for breast cancer on the grounds that new studies did not confirm that the drug helped patients.

Genentech’s approach seems intended to broaden the terms under which Avastin can remain available. The company is arguing that even if the F.D.A. reaffirms that data do not support Avastin’s effectiveness, the approval should be retained while Genentech does one more clinical trial. Avastin has remained available for breast cancer pending the appeal process.

Avastin was put on the market under an accelerated program begun in the early 1990s that allows drugs for serious diseases to be approved with less than the usual amount of evidence, subject to further studies. Dozens of drugs have been approved this way, and in at least a couple of cases approvals have been withdrawn. But this is the first time the F.D.A. will hold a hearing to consider a company’s appeal.

The debate over Avastin has evoked passions on both sides among those involved in women’s health issues. Some patient advocates argue that the F.D.A. needs to revoke the approval to maintain the integrity of the accelerated process and to ensure that cancer patients receive drugs that work.

But some breast cancer patients are expected to testify at the hearing that the drug should be kept available because it helps some women, even if not all.

“It’s so depressing to think that a federal agency can make a decision that can potentially cause me to die,” said Crystal Hanna, 35, a mother of two from Parkersburg, W.Va., who said Avastin has kept her cancer under control for almost a year.

The public comments sent to the F.D.A. before the hearing at its campus outside Washington, overwhelmingly support retaining the approval. Many of them, using virtually identical language, cite the case of Ms. Hanna, who drafted a comment for friends that circulated widely on the Internet.

Even if approval as a breast cancer treatment is ultimately rescinded, Avastin will retain approval to treat lung, colon, kidney and brain cancers. So doctors will be able to use it “off label” to treat breast cancer. But insurers might no longer pay for it for that use, putting the drug, which can cost $88,000 a year, out of reach for many women.

The Avastin issue has become caught up in the politics of overhauling health care, with some critics saying the decision not to pay for it represents rationing and others saying that Medicare should not pay for a drug that does not work. The F.D.A. maintains that it is not permitted to consider costs.

The ultimate decision will be made by the F.D.A. commissioner, Dr. Margaret A. Hamburg, who appears to have some latitude. The rules say that the F.D.A. “may” revoke the approval of a drug, but does not have to.

“Even where F.D.A. determines that confirmatory trials do not establish clinical benefit, withdrawal is not required and instead should be based on the public health considerations that motivate the accelerated approval statute,” Genentech argues in a summary of its arguments filed before the hearing.

But the F.D.A.’s drug division views the company’s request as a stalling tactic. “How many bites of the apple do you get?” Dr. Richard Pazdur, the director of the agency’s oncology drug division, said in an interview at a cancer conference early this month.

The agency, in a summary of its arguments, says that because it has already determined that the benefits of Avastin do not outweigh the risks, retaining the approval while the new study is conducted “would not be in the interest of the public health and would jeopardize the integrity of the accelerated approval program.”

Genentech and its parent company, Roche, could lose as much as $1 billion in annual sales if the breast cancer approval were revoked. Already Avastin sales for treatment of breast cancer have started declining. The drug is the world’s best-selling cancer drug, with sales last year of roughly $7 billion.

The F.D.A. approved the drug for advanced breast cancer in February 2008, after one clinical trial showed that combining Avastin with another drug, paclitaxel, delayed the median time before tumors worsened by 5.5 months, compared with using paclitaxel alone. But the women who got Avastin did not live significantly longer than those who got only paclitaxel, which is also known by the brand name Taxol.

Subsequent trials, in which Avastin was combined with different chemotherapy drugs, showed a much smaller delay in tumor progression, ranging from less than 1 month to 2.9 months. And again there was no improvement in survival for those receiving Avastin.

Based on those results and on the fact that Avastin has some life-threatening side effects, including bowel perforation and hemorrhaging, the F.D.A.’s cancer drug advisory committee voted 12 to 1 last July that the approval for the treatment of breast cancer be revoked.

The hearing this week will be before the same committee, which will make recommendations to the F.D.A. commissioner. Of the six voting committee members expected to attend, five voted to revoke the approval last July. The sixth was not at that earlier meeting. Since the data have not changed, Genentech, in the summary of its arguments, concedes it is not likely to change the committee’s mind about the benefits of Avastin.

Instead it will argue that the drug with which Avastin is combined matters. Therefore, the company should be given a chance to do another trial in which Avastin is combined with paclitaxel, as in the original trial that led to the drug’s approval.

Source: http://www.nytimes.com/2011/06/27/health/27drug.html

Safety Dooms Novel Staph Vaccine

A phase II/III trial of V710, an investigational vaccine for the prevention of Staphylococcus aureus infection, has been stopped for good following a risk-benefit analysis, according to Merck and Intercell AG.

In April, the Data Monitoring Committee recommended suspending enrollment even though a pre-specified interim analysis showed that the trial did not meet futility criteria. No explanation was given. But a decision about whether to continue the trial was put off until an analysis of the risks and benefits could be completed.

After further analysis, the Data Monitoring Committee unanimously recommended termination of the study, according to a statement from the vaccine makers.

The analysis revealed that the vaccine was unlikely to have a significant clinical benefit and may increase the risk of death and multiorgan dysfunction.

“In the additional analyses that were performed, this safety difference was not found to be statistically significant and was also determined not to warrant any action beyond routine safety follow?up,” the statement read.

The trial was designed to evaluate a single injection of V710 for preventing serious S. aureus infections in adult patients who were scheduled to undergo cardiothoracic surgery.

Merck will present the final results of the trial at an upcoming medical meeting.

Source: http://www.medpagetoday.com/InfectiousDisease/Vaccines/26921

Parkinson’s patients have double the risk of lethal melanoma, study finds

Parkinson’s disease patients have double the risk of developing potentially lethal melanoma, government researchers reported Tuesday. Researchers have long suspected such a link, but the new study, reported in the journal Neurology, provides the strongest evidence to date.

Researchers are at a loss to explain how the link occurs biologically, but they suspect it may be a combination of environmental exposure and genetic predisposition. The association is particularly strange, experts said, because Parkinson’s patients, in general, have a below-normal risk of developing most types of cancer.

Establishing a link between Parkinson’s and melanoma is difficult because both are relatively rare diseases. About 1 million Americans have a diagnosis of Parkinson’s, and about 70,000 Americans are diagnosed with melanoma each year. The number with both diseases is therefore relatively small. To increase the chances of finding statistically significant results, Dr. Honglei Chen, a neuroscientist at the National Institute of Environmental Health Sciences in Research Triangle Park, N.C., and colleagues combined the results from 12 studies conducted between 1965 and 2010, a process known as a meta-analysis. Most of the studies had fewer than 10 patients with both conditions, but combining them yielded a number large enough for statistical significance.

Overall, the researchers found that the risk of melanoma was 2.11 times normal in Parkinson’s patients. Only some of the studies broke their results down by gender. For those studies, the team found that the risk of melanoma was 2.04 times normal for men and 1.52 times normal for women. The risk of diagnosis of melanoma was significantly higher after Parkinson’s had been diagnosed. The team found no link to non-melanoma skin cancers.

Many experts had thought that the increased risk of melanoma was produced by levo-dopa, the most common treatment for Parkinson’s disease. But recent epidemiological results, Chen noted, discount that link. Among other things, the same high risk of melanoma is associated with patients who have not received the drug.

Some studies have shown that the risks of Parkinson’s and melanoma are each increased by exposure to pesticides, and that could be a common factor in the new association, the team said. Pigmentation also may play a role: Lighter hair color is associated with an increased risk of Parkinson’s and of melanoma. The genes involved may increase concentrations of the natural hormone melanin, which exacerbates the development of melanomas.

The team concluded, however, that much more research is needed to clarify the biological basis of the links.

Source: http://www.latimes.com/health/boostershots/la-heb-parkinsons-melanoma-20110607,0,818798.story?track=rss

Hazardous and untested flame retardants pervasive in baby products

A study of products designed for babies and toddlers – including car seats, nursing pillows, changing pads, bassinet mattresses and other items made with polyurethane foam – found that 80% of products tested contained chemical flame retardants considered toxic, according to a peer-reviewed study published today in the Environmental Science & Technology Journal. The same flame retardants are also found in children’s bodies and widely dispersed throughout the environment and in food.

The study analyzed 102 products for the presence of halogenated flame retardants.  Interior foam samples were tested from nursing pillows, baby carriers, car seats, changing table pads, high chairs, bassinets, portable cribs, walkers, changing pads, baby carriers, sleeping wedges, a baby tub insert, stroller, bath slings, glider rockers, and other essential child care items. Samples were submitted from locations around the United States, including two samples from Maine.

Tracy Gregoire and Steve Taylor of Topsham sent samples to the national study from the nursing pillow and bassinet mattress they used for their now two-year old son Jasiah.  The nursing pillow tested positive for Tris 2-chloro-ethyl phosphate (TCEP). TCEP was found in ten out of eleven nursing pillows analyzed.  Newborn babies often spend hours each day lying on nursing pillows; thus there is a high level of contact to babies and their mothers to this product and the flame retardants which readily escape from the pillows.

“It’s heartbreaking to think that the pillow I used to cradle my son contains chemicals that can cause long term harm to his health.  I am a well informed mother, yet given the lack of regulation, there’s just no way for parents like me to ensure toxic chemicals aren’t in the products I buy for my son,” said Tracy Gregoire, the Healthy Children’s Project Director for the Learning Disabilities Association of Maine.

The nursing pillow from Maine was one of fourteen products tested that contained TCEP, a carcinogenic flame retardant on California’s Proposition 65 list of cancer-causing chemicals. Laboratory animal studies show TCEP causes tumors in the kidney and thyroid glands. In other laboratory animal studies, TCEP has been shown to cause reductions in fertility and poor sperm quality and to interfere with brain signaling, causing hyperactivity.  TCEP is no longer produced in Europe and has been identified by Canada as posing a risk to human health.

“This study clearly shows the need for chemical policy reform at the federal level,” said Steve Taylor, Program Director of the Environmental Health Strategy Center, a Maine based public health organization that has led successful campaigns to phase out use of flame retardants known as Penta, Octa and Deca in electronics, mattresses, shipping pallets, and other products sold in Maine.  “Maine lawmakers have taken important steps to protect people from exposure to toxic flame retardants however we can’t go it alone.  We’re asking Senators Snowe and Collins to support the Safe Chemicals Act of 2011 to ensure there’s a federal law that works to ensure common consumer products are safe for our families.”

The Toxic Substances Control Act (TSCA) is the federal law tasked with regulating use of chemicals in the U.S.  but TSCA is widely perceived to have failed to protect public health, having regulated only 5 chemicals in its 35 years of existence out of the 80,000 chemicals in use in the U.S.

An effort to strengthen TSCA is underway in Congress in the form of the Safe Chemicals Act of 2011 sponsored by Senator Lautenberg.  This bill would require basic health and safety data for chemicals, reduce exposure to the most harmful chemicals, identify and address “hot spots” where people are more exposed to toxic chemicals, and prevent new harmful chemicals from hitting the marketplace unless they are tested and found to be reasonably safe.

The baby products study, Identification of Flame Retardants in Polyurethane Foam Collected from Baby Products, is available in the current issue of the Environmental Science & Technology Journal. Other results from the new baby product testing include:

  1. Four products contained penta-BDE, a substance so toxic it is banned in 172 countries and 12 U.S. states including Maine, and subject to a national phaseout.
  2. 29 products contained TDCPP or chlorinated Tris, a possible human carcinogen that was removed from children’s pajamas over health concerns in the late 1970s. In animal studies, chlorinated Tris has been associated with cancer of the liver, kidney, brain and testis, among other harmful effects.
  3. 16 products contained Firemaster 550/600 flame retardants for which EPA has predicted toxicity concerns and required additional testing.
  4. 14 products contained TCPP, which is similar in chemical structure to Chlorinated Tris and TCEP and has limited health information.

“Toxic or untested flame retardants like the ones found in this study can migrate out of products and end up in our homes and our bodies.  These chemicals are associated with reduced IQ, increased time to pregnancy, endocrine and thyroid disruption, and impaired child development,” says Arlene Blum, PhD, a co-author of the study and executive director of the Green Science Policy Institute. Blum’s early research contributed to the removal of Tris flame retardants from children’s pajamas in the 1970’s. “I was surprised to find Tris back in high levels in the foam in baby products.”

According to Environmental Health News, researchers have found that adults in the United States have average levels of flame retardant chemicals in their bodies that are 20 times higher than Europeans. A study in California found households tested had 200 times more brominated flame retardants in household dust than European homes.  Meanwhile, the Centers for Disease Control & Prevention report that over 90% of the U.S. population carries flame retardants in their bodies.

Microneedle Drug Delivery Systems Moving Toward Commercialization by Converging with Existing Delivery Technologies

Evolutionary Design Enhancements Creating a Viable Path to the Market According to Greystone Research Associates

(Amherst, NH) – For the past decade a small group of device development companies, often supported by academic partners and national government technology transfer programs, have been attempting to commercialize drug delivery products based on arrays of microneedles. By creating channels in the stratum corneum, these devices were expected to deliver therapeutic drugs across the skin and into the dermal layers. While several product efforts focused on achieving a local anesthetic effect, the majority pursued a pharmacokinetic model that involved migration of the API via interstitial fluid to the vasculature to achieve systemic delivery.

After years of prototyping unique array designs, a several development programs have migrated toward improving the performance of existing delivery methods. While novel microneedle designs still exist, the evolving landscape can now be grouped into three main strategic approaches: (1) arrays mounted on the end of syringes to effect an injection with minimal discomfort; (2) stand-alone drug-containing devices (coated microneedles or microneedle reservoir patch) designed to be applied or attached to the skin directly; (3) two-step delivery systems that employ an array to create microchannels through the skin followed by a drug-containing patch designed to deliver the drug through the newly-formed microchannels.

Microneedle technology is attaining commercial viability at a time when drug developers are faced with new challenges as they assess ways to administer a new class of compounds with significant therapeutic potential. The commercialization of microneedle drug delivery devices such as the sanofi-aventis Intanza influenza vaccine, which is based on the Becton Dickinson Soluvia syringe-mounted microneedle array device, is a milestone in the transition of microneedle drug delivery from development to market place. Microneedle technology promises to impact health care by allowing the precise injection of therapeutic agents to prescribed locations below the skin.

A new research study, Microneedle Drug Delivery: Technology, Devices, Players, Markets and Prospects analyzes existing and emerging microneedle delivery products, product candidates and development programs, profiles market participants, and assesses key demand and technology factors influencing the commercial market and shaping growth in this sector.

More information is available at www.greystoneassociates.org .

About Greystone

Greystone Research Associates is a medical technology consulting firm focused on the areas of medical market strategy, product commercialization, venture development, and market research. We assist medical and healthcare market participants in achieving their business objectives through the creation of detailed development strategies, product commercialization programs, and comprehensive market and technology research and analysis. Our market research publications are designed, researched and written to provide timely and insightful information and data on focused market segments, with the aim of providing market participants with the essential knowledge to refine and execute their marketing plans and financial targets.

Contact:

Mark Smith
Voice: 603-595-4340
Fax: 603-804-0466
www.greystoneassociates.org

Source: Greystone Research Associates

Accessing Nuclear Receptors with ActiTarg-N

TimTec adds new targeted library to its ActiTarg Series. ActiTarg-N gathers 1040 nuclear receptors ligands analogs. Nuclear receptors are inside-cell proteins that regulate gene transcription and affect wide range of biological functions throughout organism normal and pathological development. These are the super-family of 48 structurally related transcription factors that can be regulated by small molecules. The search for the small molecule or its defining features is one of the priorities of contemporary life-science R&D.

TimTec uses “focused diversity” approach in designing the screening collection of nuclear receptor ligands analogs. Analogs compound pool started with about ninety “de-fragmented” known ligands. The following targets were primarily considered in the design: ER, estrogen receptor and estrogen related receptor; AR, androgen receptor; GRR, glucocorticoid receptor; RAR, retinoic acid receptor; THR, thyroid hormone receptor; VDR, vitamin D receptor; FXR, Farnesoid X Receptor; PPARa/y, Peroxisome proliferator-activated receptors; LXR, liver X receptor; CCR5, C-C chemokine receptor type 5; MRR, mineralocorticoid; PR, progesterone receptor; CAR, Constitutive androstane receptor.

TimTec stock was scanned to identify molecules with the same known ligands fragments, which re-assembled themselves in the new combinations of chemical possibilities. Additional computational manipulations drew in more compounds with overall structural similarity to known molecules. As a result ActiTarg-N presents desirable chemical diversity with the sharp focus on the target group.

Contact for more information and free consultation scheduling:

TimTec LLC
Harmony Business Park A-301
Newark DE 19711
Tel 302 292 8500
Fax 302 292 8520
info@timtec.net

Web: http://www.timtec.net/actitarg-n-nuclear-receptor-ligands.html

About TimTec

TimTec LLC is a privately held company located in Newark Delaware, USA. It was founded in 1995 and began its work in the areas of acquisition and distribution of synthetic organic and natural compounds, custom synthesis, and laboratory equipment to become a full service partner for drug discovery. TimTec has developed strong in-house expertise in the design of screening products to offer full line of libraries and compound sets of various specialization for different in capacity/size and purpose assays.

TimTec compound collections offer greater diversity since the company has balanced combination of in-house synthesis and outside sourcing. TimTec compounds are stored in dry form only and are freshly prepared in DMSO to orders. The company does compound management and custom formatting. Global customers include major pharmaceutical, biotech, agricultural, and educational organizations that use TimTec products and services for research and development programs.

http://www.timtec.net/

Michigan develops its first disease specific embryonic stemcell lines

Researchers at the University of Michigan have created the state’s first human embryonic stem cell lines that carry the genes responsible for inherited disease. The achievement will enable university scientists to study the onset and progression of genetic disorders and to search for new treatments.

With this accomplishment, the U-M joins a small handful of U.S. universities that are creating disease-specific human embryonic stem cell lines.

“All our efforts are finally starting to bear fruit,” says Gary Smith, co-director of the U-M Consortium for Stem Cell Therapies and leader of the cell-line derivation project. “Creating disease-specific human embryonic stem cell lines has been a central goal of the consortium since it was formed two years ago, and now we’ve passed that milestone.”

One of the lines carries the genetic defect that causes hemophilia B, a hereditary condition in which the blood does not clot properly. The other carries the gene responsible for Charcot-Marie-Tooth disease, a hereditary neurological disorder characterized by a slowly progressive degeneration of the muscles in the foot, lower leg and hand.

If embryos are created for reproductive purposes but are found to be unsuitable for that use because they carry disease, Michigan law allows those embryos to be donated for research instead of discarded. At that stage of development, the donated embryos consist of a cluster of cells about the size of the period at the end of this sentence.

“These are the first of many disease-specific human embryonic stem cell lines that researchers at the U-M Consortium for Stem Cell Therapies intend to develop,” says consortium co-director Sue O’Shea, a professor of cell and developmental biology at the Medical School.

In the months and years ahead, donated embryos will be used to create cell lines that carry the genes responsible for myotonic dystrophy, Huntington’s disease, Rett syndrome, spinal muscular atrophy and Tay-Sachs disease, for example.

“This announcement puts the University of Michigan at the very forefront of stem cell research,” says Dr. Eva Feldman, director of the U-M’s A. Alfred Taubman Medical Research Institute.

“We will be one of the few institutions in the country to be creating embryonic stem cell lines targeted at understanding and treating specific inherited diseases,” Feldman says. “These stem cell lines hold so much promise for medical science, and for this reason, they will be of tremendous interest to researchers around the world.”

The consortium will distribute samples of the new lines to researchers across campus and to collaborators statewide. In addition, U-M researchers intend to submit the lines to the U.S. National Institutes of Health for inclusion in the national registry of human embryonic stem cell lines that are eligible for federal research funding.

The two new U-M lines would be the only lines on the federal registry to carry the genes for hemophilia B and Charcot-Marie-Tooth disease. Currently there are three disease-specific lines on the federal registry, which contains 91 human embryonic stem cell lines.

These are the second and third human embryonic stem cell lines created by U-M consortium researchers. The first line was announced in October and was derived from a genetically normal 5-day-old embryo created for reproductive purposes but no longer needed for that use and donated to the university.

The creation of all three lines was made possible by Michigan voters’ November 2008 approval of Proposal 2, a state constitutional amendment permitting scientists here to derive human embryonic stem cell lines using surplus embryos from fertility clinics.

The amendment also made possible an unusual collaboration that has blossomed between the university and a company that describes itself as “the leading global provider” of pre-implantation genetic diagnosis (PGD) tests, Genesis Genetics of Detroit. PGD is a testing method used to identify days-old embryos carrying the genetic mutations responsible for inherited diseases.

Genesis Genetics performs nearly 4,000 PGD tests annually at its Detroit facility. Under the arrangement between the company and the university, patients with embryos that test positive for a genetic disease now have the option of donating those embryos to the Consortium for Stem Cell Therapies if they have decided not to use them for reproductive purposes and the embryos would be discarded otherwise.

The agreement was worked out between U-M’s Smith and Dr. Mark Hughes, founder and president of Genesis Genetics and a pioneer in the field of pre-implantation genetic diagnosis.

“This is an example of two Michigan leaders — U-M and Genesis Genetics — joining forces to advance medicine by thinking outside the box,” says Smith, a professor of obstetrics and gynecology at the Medical School.

“This is an innovative collaboration and one that did not happen overnight,” Smith says. “This is an arrangement that’s been worked on for more than two years.”

During a PGD test, a single cell is removed from an eight-celled embryo. The other seven cells continue to multiply and on the fifth day form a cluster of roughly 100 cells known as a blastocyst.

The U-M consortium received the first disease-affected blastocysts through Genesis Genetics in November and began trying to establish a human embryonic stem cell line — a collection of millions of genetically identical cells generated from a single embryo.

“These are very precious cells, and it would be unconscionable not to take advantage of such an opportunity for medical science and the cure of disease,” Hughes says.

Genesis Genetics has a similar arrangement with Stanford University. Until the Michigan constitutional amendment passed in November 2008, Hughes says, he “hadn’t even imagined that I could work with a top-flight institution right down the road, like the University of Michigan, because the state didn’t allow such work.”

Once the two new lines were established, various tests were performed to confirm that the cells displayed traits of normal embryonic stem cells. Conducting those tests is called characterizing an embryonic stem cell line. The characterization tests were completed this month.

Hemophilia B, also known as Christmas Disease, is the less common form of the disorder and is caused by the lack of clotting Factor IX. Charcot-Marie-Tooth disease is one of the most common inherited neurological disorders, affecting one in 2,500 people in the United States. People with CMT usually begin to experience symptoms in adolescence or early adulthood.

“The creation of these cell lines will provide a new tool that will help the international scientific community improve the treatment of these diseases,” says Sean Morrison, director of the U-M Center for Stem Cell Biology.

The U-M cell-line derivation project was approved by the university’s Human Pluripotent Stem Cell Research Oversight Committee and the Medical School’s Institutional Review Board. Both committees are composed of physicians, scientists, ethicists, attorneys and community members who concluded that the project would be conducted ethically, legally and to the benefit of patients.

“This scientific breakthrough demonstrates the wisdom of the voters of Michigan, who realized the importance of stem cell research for the health and well-being of the state,” says A. Alfred Taubman, founder and chair of the A. Alfred Taubman Medical Research Institute.

“We have become global leaders in the science of stem cells,” he says. “We are producing tools that can be of immeasurable aid to scientists studying such disorders as hemophilia and Huntington’s disease. And we are just beginning to scratch the surface of this new scientific frontier.”

Source: http://www.speroforum.com/a/51500/Michigan-develops-its-first-disease-specific-embryonic-stemcell-lines

Fragment Library

Thermo Fisher Scientific Inc. announced that its Maybridge Ro3 Diversity Fragment Library has helped researchers validate an emerging technique for drug discovery that targets key protein receptors involved in a wide range of biological functions.

David Myszka, founder of Biosensor Tools LLC and director of the Center for Biomolecular Interaction Analysis at the University of Utah, used surface plasmon resonance (SPR) to screen small molecules (fragments) in the Maybridge Ro3 collection against stabilised G-Protein Coupled Receptors (GPCRs) provided by Heptares Therapeutics1. Several new classes of compounds were identified from the Ro3 library, which is accelerating drug discovery efforts around these receptors

Dr. Myszka’s study demonstrated for the first time that fragment screening by SPR is an effective approach. It utilises the sensor surface to purify and concentrate solubilised tagged GPCRs and then characterise their binding activities with the fragments. Dr. Myszka and Rebecca Rich, a research scientist in Dr. Myszka’s group, recently presented their work, “Fragment Screening against Membrane Receptors using SPR,” at the Fragment-Based Lead Discovery Conference in Philadelphia and at the Developments in Protein Interaction Analysis symposium in Barcelona, Spain.

“While fragment screening by SPR has become standard practice, this is the first example of a successful SPR-based fragment screen against GPCRs,” said Dr. Myszka. “One major factor contributing to our success was the integrity of the Maybridge Ro3 Fragments. The library was well-behaved in terms of high solubility and displayed minimal nonspecific binding or so-called promiscuous binders. In addition, the structural diversity within this library allowed us to span a lot of chemical space, helping us to identify subsets of novel compounds that targeted two GPCRs. From the primary screen we identified thematic structural elements in the hits and then selected analogs from within the full Maybridge collection to investigate as confirmatory hits. With these follow-up studies in hand, we are now poised to pursue the next stage in elaborating compounds for drug development.”

“The guaranteed aqueous solubility of Maybridge Ro3 Fragments is not only key from a practical perspective, but it also provides an insight into likely ADME problems as the hits are evolved into drug-like molecules,” said Simon Pearce, product manager for Maybridge products at Thermo Fisher Scientific. “Furthermore, pharmacophoric enrichment and quality assurance of at least 95 percent, with full Rule of Three (Ro3) compliance, meant that all fragments used for the study possessed physicochemical properties that also increased the probability of successful hits.”

Thermo Fisher Scientific and Dr. Myszka are continuing their collaboration as the study now expands to drug development using additional Maybridge Ro3 Fragments.

Source: Thermo Fisher Scientific, Inc and DDDMag.com

Panel calls for new safety review of mercury dental fillings

Updated data on mercury amalgam dental fillings may indicate possible medical problems for patients, a Food and Drug Administration advisory committee said Wednesday.

The panel — after hearing two days of testimony from experts, members of the public and dental professionals — recommended the FDA look at information updated since the agency ruled in 2009 that the mercury in dental fillings is not harmful.

Committee members noted, however, that the FDA’s decision was solid, based on information available at the time. The committee also stressed that more studies need to be done on amalgam fillings, especially in children.

Public pressure prompted the panel’s review, initiated less than 18 months after the agency’s decision.

Committee members listened to testimony by consumer and dental groups claiming the FDA used flawed science when it set the current guidelines for mercury safety levels.

“We need to see where the science is and if there are gaps.” said the panel’s chairwoman, Dr. Marjorie Jeffcoat, a dentist and researcher with the University of Pennsylvania.

In its final rule, the FDA concluded clinical studies did not establish a causal link between dental amalgam and health problems in people age 6 and older. But it did add that developing fetuses and young children may be more sensitive to the neurotoxin.

Amalgam tooth fillings are an alloy made up of various metals and 50 percent mercury,

Mercury toxicity has been well documented, but when it comes to amalgam fillings there isn’t a lot of data. Many dentists favor these fillings because they are cheap, easy to put in place and durable.

Dental professionals also argue that mercury fillings last longer than resin composites, and are easier on the tooth. The American Dental Association agrees with the FDA that amalgam fillings are safe.

Yet, some experts say mercury from these fillings penetrates into the body and damages human cells, especially in the brain, bones and kidneys. How much damage it is unknown, which is why the advisory committee is revisiting the issue.

In Wednesday’s public hearing, 30 people testified for and against the use of amalgam fillings.

Jessica Kerger, an attorney from Toledo, Ohio, said she was a healthy child until she started getting amalgam fillings. As she got older, she faced numerous health problems and a variety of diagnoses. She even had her amalgam fillings removed. It wasn’t until a doctor tested her for mercury poisoning that she realized her problem, she said.

Now, after being treated for excess mercury in her body, Kerger said, “I’m an active mother, attorney and I have a black belt in karate. I blame my fillings and I am begging the FDA to get rid of them.”

While others testified that mercury in their fillings caused such health problems as loss of memory, impaired vision, miscarriages and paralysis, many dental professionals asked that amalgam fillings remain.

Addressing the board, Dr. Vincent Mayher, a former president of the Academy of General Dentistry, said public accusations that dentists force patients to receive amalgam fillings is exaggerated.

“It’s Inflammatory. No dentist I know of forces a patient at any time to get amalgam fillings these days, especially pregnant women and little children.” Mayher testified

Andrew Read Fuller, a dental student at UCLA and member of the American Student Dental Association, noted there is no scientific data that amalgam fillings cause the problems some attribute to them, and said that, as a future dentist, he would use amalgam fillings on any of his patients as well as himself.

“In the absence of new evidence there is no reason to question the FDA’s decision.” Fuller said.

Yet some dentists did say they would avoid using amalgam fillings because of numerous public reports of mercury poisoning.

“I always wondered why we were told by the (American Dental Association) to be careful when disposing of mercury. If it’s so dangerous to the environment, why not my patients?” asked Dr. Stephen Markus, a dentist in the Philadelphia area.

The committee also recommended that the FDA come up with models that could be used to look at the effects of mercury vapor exposure from dental fillings. And when designing these models, it said, the agency should take into consideration age, health history and physical makeup of individuals.

There was also discussion that more data needs to be looked at to come up with stronger models, especially those based on younger children and unborn fetuses.

More information on amalgam fillings should be posted for both for patients and dentists, the committee said.

It also noted the FDA’s biomarker using urine to detect mercury exposure is not perfect but is the best available for adults. Members also noted that more updated data is needed before the agency can make stronger guidelines on amalgam fillings.

Although the committee’s recommendations will go to the FDA board for consideration, the board does not have to follow them. Traditionally, however, it does.

Source: CNN.com

Caliper Continues Participation in EPA’s Expanded ToxCast Program; Receives Remaining Phase II Compounds for Screening in Fourth Quarter

HOPKINTON, Mass., Dec. 7, 2010 /PRNewswire-FirstCall/ — Caliper Life Sciences, Inc. (Nasdaq: CALP), a leading provider of tools and services for drug discovery and life sciences research, today announced that the company has received the remaining balance of the compound library for the Environmental Protection Agency’s (EPA) Phase II ToxCast? screening program.

The United States Environmental Protection Agency (EPA) announced the next phase of toxicity screening, in which a total of 1,000 chemicals (300 compounds in Phase 1 and 700 additional compounds in Phase II) will be screened as part of EPA’s ToxCast initiative. Caliper’s participation in this program, first announced in 2007, involves the application of extensive and diverse proprietary assay and screening technologies.

“The Caliper team is very pleased with our contributions to ToxCast to date, and we’re excited to receive the remaining compounds (350 Phase IIb compounds) for the EPA’s Phase II ToxCast screening program,” said Kevin Hrusovsky, President and CEO of Caliper Life Sciences. “Receiving this most recent compound set will allow our scientists to complete Phase IIb compound screening over the next several months, and will likely push Caliper’s revenue to the top end of our corporate revenue guidance range for the fourth quarter and full year.”

The ToxCast program was initiated to speed up the identification of potentially toxic compounds and the impact of chemical exposure on the human body. The program relies on innovative research approaches that predict toxicity while minimizing reliance on animal models. Caliper Discovery Alliances and Services’ (CDAS) predictive toxicity panel has been used in the EPA ToxCast screening program, and increasingly by pharmaceutical, agricultural and cosmetic companies, to assess potential chemical toxicity of their compounds in commercial development. The EPA recently announced the screening of 1,000 chemicals under the ToxCast program.

The CDAS assays use human and animal proteins which mediate key biological functions in the body to screen for possible adverse or toxic effects of chemicals. Caliper recently initiated testing of the second half of the 700 chemicals that comprise Phase II of the ToxCast screening program through the CDAS in vitro panel, which includes over 230 such assays.

Many of the chemicals being tested in the ToxCast program are components of industrial and consumer products, as well as agrichemicals and pharmaceuticals, which were previously tested for in vivo toxicity using live animals. By comparing the in vitro data being generated by CDAS under the ToxCast program with the known in vivo effects of these ToxCast library compounds, the predictive potential of the in vitro assays can be determined. The EPA is tasked with testing thousands of compounds and chemicals each year, which has led to a significant backlog in the regulatory approval process. The goal of the ToxCast program is to reduce the EPA’s dependence on expensive and lengthy animal testing and implement solutions that enable faster identification of harmful chemicals at a lower cost and with higher accuracy.

For additional details about the current status of EPA ToxCast program, please visit the EPA news announcement “EPA Screens 1,000 Chemicals Using ToxCast” at http://yosemite.epa.gov/opa/admpress.nsf/d0cf6618525a9efb85257359003fb69d/73ec2518e34bc93d852577eb0060dd7c!OpenDocument.

About Caliper Life Sciences

Caliper Life Sciences is a premier provider of cutting-edge technologies enabling researchers in the life sciences industry to create life-saving and enhancing medicines and diagnostic tests more quickly and efficiently. Caliper is aggressively innovating new technology to bridge the gap between in vitro assays and in vivo results, enabling the translation of those results into cures for human disease. Caliper’s portfolio of offerings includes state-of-the-art microfluidics, lab automation and liquid handling, optical imaging technologies, and discovery and development outsourcing solutions. For more information please visit www.caliperLS.com.

The statements in this press release regarding future events, including statements regarding Caliper’s expectation that its revenue for the fourth quarter and full year 2010 will be at the top end of its previously announced guidance, are “forward-looking statements” within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those contemplated by the forward-looking statements as a result of a number of factors, including that unanticipated difficulties may be encountered in Caliper’s fulfillment of its obligations under the EPA ToxCast program. Further information on risks faced by Caliper are detailed under the caption “Risks Related To Our Business” in Caliper’s Annual Report on Form 10-K for the year ended December 31, 2009. Our filings are available on a web site maintained by the Securities and Exchange Commission at http://www.sec.gov. Caliper does not undertake any obligation to update forward-looking or other statements in this release or the conference call.

Caliper is a trademark of Caliper Life Sciences, Inc. ToxCast is a trademark of the Environmental Protection Agency.

SOURCE Caliper Life Sciences, Inc.

Team discovers new type of anti-malarial compound

LA JOLLA, CA – August 30, 2010 –– An international team led by scientists from The Scripps Research Institute, the Swiss Tropical Institute, the Genomics Institute of the Novartis Research Foundation and the Novartis Institute for Tropical Diseases has discovered a promising new drug candidate that represents a new class of drug to treat malaria. Clinical trials for the compound are planned for later this year.

The research was published on September 3, 2010, in the prestigious journal Science.

“We’re very excited by the new compound,” said Elizabeth Winzeler, a Scripps Research associate professor and member of the Genomics Institute of the Novartis Research Foundation (GNF) who led the research with Thierry Diagana of the Novartis Institute of Tropical Diseases. “It has a lot of encouraging features as a drug candidate, including an attractive safety profile and potential treatment in a single oral dose.”

The Problem with Malaria

Malaria is a nasty and often fatal disease, which may lead to kidney failure, seizures, permanent neurological damage, coma, and death. The disease is caused by Plasmodium parasites, transmitted through the bite of infected mosquitoes.

Despite a century of effort to globally control malaria, the disease remains endemic in many parts of the world. According to the World Health Organization, in 2008 there were 247 million cases of malaria and nearly one million deaths – mostly among children living in Africa. The need for new treatments is made more urgent by the spread of drug-resistance to current medications.

While some 40 percent of the world’s population lives in malaria-infected areas, little economic incentive for pharmaceutical companies to develop new treatments exists, since malaria-infected areas correspond with the some of the world’s most impoverished nations.

To help surmount this barrier, concerned individuals have formed public-private partnerships to help spur research on much-needed treatments. The current study is the result of one such partnership. In addition to in-kind contributions by the pharmaceutical company Novartis (including its decade-old Novartis Malaria Initiatives) and the scientific expertise of scientists in academic laboratories around the world, the research was made possible by the support of the nonprofit organizations Medicines for Malaria Venture, the Wellcome Trust, and the W. M. Keck Foundation, as well as funding from government agencies in the United States (the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) and Singapore (Agency for Science, Technology, and Research (A*STAR)).

In Pursuit of a New Drug

The impetus for the new study began in the Scripps Research Winzeler laboratory about seven years ago when Winzeler received funding from the Keck Foundation to develop new antimalarial drugs by pursuing target-based drug discovery methods (designing a drug based on known molecular interactions). The approach was not yielding many interesting compounds, so Winzeler and her collaborators at GNF decided to take a different tack.

Noting that serendipity and observation played a role in all previous breakthrough antimalarials (for example, the drug artemisinin was derived from an herb used in traditional Chinese medicine), the team decided to pursue cell-based screening. The Winzeler lab at GNF then developed a high-throughput screen to look for compounds active against the malaria parasite Plasmodium falciparum. Scientists at Novartis, which had compiled a library of 12,000 purified natural products, then offered their library for the screen.

The first screen returned a set of 275 compounds with anti-malarial activity. Subsequent screens weeded out those with little activity against multi-drug resistant parasites and those toxic for mammalian cells. Seventeen compounds remained in the running.

An evaluation of the remaining compounds’ toxicity and pharmacokinetic profiles provided additional information to evaluate their potential drug candidates. One compound—belonging to a chemical class of molecules called spiroindolones, which had never before been associated with anti-malarial activity—stood out as particularly promising.

Novartis Institute for Tropical Medicine’s project team head Bryan Yeung noted, “Of the remaining compound classes, the spirotetrahydro-beta-carbolines or spiroindolones displayed the desired physicochemical properties for drug development, as well as a mechanism of action distinct from the currently used therapies based on aminoquinolines and artemisinin derivatives.”

In an effort based at the Novartis Institute of Tropical Diseases in Singapore, the chemistry team synthesized and evaluated some 200 derivatives of this molecule to optimize its safety profile and pharmacokinetic properties. At the end of several hundred rounds of medicinal chemistry and efficacy testing at the Swiss Tropical and Public Health Institute, the team advanced NITD609 as the best candidate for proceeding to clinical trials.

Shining Light in the Black Box

The new study, however, doesn’t stop there. To gain insight into how NITD609 worked, Winzeler applied a distinctive and elegant evolutionary approach.

Winzeler noted, “One of the disadvantages of doing cellular screening has been chemists will say, ‘You don’t know what the target is. You don’t know if the parasites are going to become resistant to it. It’s a huge black box.’ It has been extremely difficult to find the genes involved in malarial drug resistance using traditional methods. So what we’ve been doing in my lab is developing ways to find single-base changes in drug-exposed genomes.”

In this case, Case McNamara at GNF, a lead author, took a parasite and cloned it to create two identical organisms. One was allowed to reproduce in regular culture. The other was placed in a culture with a sub-lethal dose of the anti-malarial drug candidate. After three to four months and many generations, the parasites in the culture with NITD609 started to display low-level drug resistance.

At that point, the team used an advanced tiling array to compare the 26 million base pairs of coding sequence in the genome of the drug-exposed organisms to the genome of the control organisms.

“We were expecting hundreds or thousands of mutations because we grew the parasites for many generations,” Winzeler said. “We got only a handful.”

When McNamara analyzed the genomes of the six resistant clones, it turned out that all of the mutant strains had at least one mutation mapping to a single gene, pfatp4. This suggests that the protein PfATP4 is either the target for the new drug candidate or is involved in the parasite’s resistance to it in some other way.

“PfATP4 is a cation transporting ATPase, so it is a very well validated drug target,” said Winzeler. “That class of proteins, for example, is the target of antacids. It hasn’t really been explored in malaria. This is one of the first cases where an evolution study has been used to identify the action of a compound in a parasite cell.”

Source: sciencecodex.com

Molecular Target for Screening: G-Protein-Coupled Receptors

Newark, DE. August, 2010 – Press Release – TimTec, LLC. – Molecular Target for Screening:  G-Protein-Coupled Receptors, ActiTarg-G

G-Protein-Coupled Receptors are the largest gene families in the human genome and, rightfully so, have become the leading molecular target in 2008. In 2009 SBS April meeting in Lille, France, followed-up with screening trends report stating that  “GPCRs are expected to replace protein kinases as the most common molecular target used by HTS laboratories.”

GPCRs are the largest family of cell surface receptors being integral to the number of cellular and physiological functions, including light sensing, smell, appetite control, insulin secretion, and blood pressure modulation. These receptors generally have a seven-membrane spanning alpha-helical topography, and while these receptors are similar in overall structure and function, they differ in key amino acid residues. The potential for this super family of receptors to reveal small molecule modulators of a significant biological function has been responsible for the focus of intense drug discovery efforts.

TimTec GPCR Ligands library is called ActiTarg-G. It currently counts 2,300 molecules available in various formatting options, and can be delivered in vials or in 96 or 384-well plates.  ActiTarg-G is the set of diverse molecules that contain chemical lattices present in compounds reported in the technical or patent literature to possess GPCR-ligand properties.

Contact Information to schedule free consultation:

TimTec LLC

Harmony Business Park A-301

Newark DE 19711

Tel 302 292 8500

Fax 302 292 8520

info@timtec.net

Web: http://www.timtec.net/news/timtec-news/actitarg-g-gpcr-ligandshtml.html

About TimTec

TimTec LLC is a privately held company located in Newark Delaware, USA. It was founded in 1995 and began its work in the areas of acquisition and distribution of synthetic organic and natural compounds and collections, custom synthesis, and laboratory equipment to become a full service partner for drug discovery. TimTec has established a global network of thousands of scientists from research centers around the world. International customers include major pharmaceutical, biotech, agricultural, and educational companies and institutions, which use TimTec products for research and development programs.

http://www.timtec.net/

Actelion obtains option to acquire privately-held Trophos

Late-stage Phase III compound in Amyotrophic Lateral Sclerosis to report data in late 2011 – Novel therapeutic approach to be further explored in drug discovery collaboration

ALLSCHWIL, SWITZERLAND and MARSEILLE, FRANCE – 20 July 2010 – Actelion Ltd (SIX: ATLN) and privately-held Trophos SA announced today that they have entered into a binding agreement whereby Actelion has, for EUR 10 million, obtained an exclusive option to acquire privately-held Trophos SA, a clinical stage pharmaceutical company.

Trophos’ lead compound olesoxime has completed enrollment into a Phase III study in Amyotrophic Lateral Sclerosis (ALS), an orphan disease also known as Lou Gehrig’s disease. This study is expected to report data by the end of 2011; at this time Actelion may exercise the option for an acquisition price between EUR 125 and 195 million in cash, contingent on different regulatory approvals and other clinical progress of Trophos’ pipeline.

Simon Buckingham, President, Global Corporate and Business Development: “Trophos has done an excellent job to enroll more than 500 ALS patients into a well-designed pivotal study. Once study results are available, Actelion is ideally positioned to leverage these achievements with our proven global regulatory and marketing expertise in the area of orphan drugs.”

Trophos is a clinical stage company with a pipeline of new molecular entities in development for the motor neuron diseases ALS and spinal muscular atrophy (SMA) as well as a novel compound for cardiac ischemia-reperfusion injury.

Damian Marron, Chief Executive Officer at Trophos commented: “Since its inception, Trophos has made significant progress in turning its key expertise in neurodegenerative disorders and orphan diseases into achievements that include advancing our lead compound olesoxime into late stage clinical development. The development of olesoxime has benefited from significant support from patient communities, clinical investigators and the European Union (EU), including Trophos spearheading an EU-funded consortium dedicated to improving the treatment of ALS.”

Damian Marron continued: “We are delighted with the option agreement with Actelion, which will bring additional expertise and competencies to enable Trophos’ compound to rapidly reach patients following a successful study outcome.”

Damian Marron concluded: “I am also pleased with the option agreement as it provides the Trophos’ investors an opportunity to realize the value of their investments.”

The two companies also agreed on a research collaboration to allow Actelion access to Trophos’ proprietary CNS assay technology and compound library. The technology mimics neuronal degeneration processes in the test tube and is used to screen chemical compounds for their ability to block these processes.

Martine Clozel, MD and Chief Scientific Officer at Actelion commented: “Trophos has a pioneering approach and proprietary expertise that has enabled the development of high throughput screens using primary neurons as well as the ability to broadly profile more advanced compounds. This is of great value to Actelion as we have developed a large inhouse compound library and significant expertise in the field of neurological disorders.”

###
Notes to Editor
About the agreement

On July 19, 2010, Actelion signed an acquisition agreement to purchase Trophos SA, a French clinical stage pharmaceutical company developing drugs for patients with neurodegenerative diseases. The acquisition is contingent on the exercise of an option, whereas Actelion has the right to terminate the agreement at any time during the option period. The option will become effective upon payment of EUR 10 million by Actelion and end two months after Actelion’s receipt of the results of an ongoing Phase III study with olesoxime but not later than December 31, 2012. The purchase consideration will be paid in cash and is partially contingent on market approval of olesoxime by the US Food and Drug Administration (FDA) as well as overall pipeline progression of other compounds. Consequently, the purchase price might vary between EUR 125 million and 195 million.
About Olesoxime

Olesoxime is Trophos’ lead compound of a proprietary mitochondrial pore modulator series. Preclinical studies have demonstrated that olesoxime promotes the function and survival of neurons and other cell types under disease-relevant stress conditions, through interactions with the mitochondrial permeability transition pore (mPTP). Olesoxime has been shown to be active in the SOD1 model of ALS (Bordet et al., JPET 322:709-720, 2007).

Phase I studies in healthy volunteers and Phase Ib studies in ALS patients demonstrated that olesoxime is well-tolerated. These studies also helped to determine the dose regimen used in the pivotal Phase III study.
About the Phase III study in ALS

The study is an 18-month randomized, parallel group, double-blind, placebo-controlled trial evaluating the efficacy and safety of olesoxime against placebo and has benefited from protocol advice obtained from the European Medical Agency EMA. The study completed enrollment in the first quarter of 2010 with 512 patients diagnosed with ALS between 6 and 36 months before enrollment and receiving standard of care. Olesoxime is dosed at 330 mg once-a-day oral capsules. The study is being undertaken in 15 centers in France, Germany, UK, Belgium and Spain and is part of a 3-year collaborative project named MitoTarget (Grant Agreement No: HEALTH-F22008-223388) for which the European Commission has awarded a grant of nearly EUR 6 million.

The primary endpoint of the study is the overall 18-month survival rate. Secondary endpoints include the ALS Functional Rating Scale, time to assisted ventilation, vital capacity (a measure of respiratory function), Manual Muscular Testing and quality of life.
About Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS), often referred to as “Lou Gehrig’s Disease”, is the most common motor neuron disease with a prevalence of 2-3 per 100,000 (30,000 patients in US; 45,000 in Europe at any given time).

Most people who develop ALS are between the ages of 40 and 70 (average age of 55) and over 80% die three to five years after diagnosis. The most common form of ALS is sporadic, but 5-10% of cases are inherited in a dominant manner (familial ALS).

Early symptoms of ALS include muscle weakness in arms and legs; later difficulties in breathing and swallowing are generally the cause of death. There is no treatment today that halts disease progression in ALS patients.
About Trophos’ discovery strategy

The Trophos discovery strategy involves recreating neuronal degeneration processes in the test tube and screening chemical compounds for their ability to block these processes. Diseaserelevant assays are developed using the specific neurons affected in each disease, for example: motor neurons for amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), striatal neurons for Huntington’s disease and cortical neurons for Alzheimer’s Disease. In essence, Trophos considers the neuron as a cellular test tube filled with the diverse products of the 30,000 genes expressed by the cell under the conditions that are as close to the physiological environment as possible.
About Trophos SA

Trophos SA is a clinical stage pharmaceutical company developing innovative therapeutics for indications with under-served needs in neurology and cardiology. The company has a novel and proprietary cholesterol-oxime based chemistry platform generating a pipeline of drug candidates with the lead product, olesoxime, fully enrolled in a Phase III study in ALS patients and a second product in the cardiovascular field entering Phase I clinical development. Trophos’ mitochondrial pore modulator compounds enhance the function and survival of stressed cells via modulation of dysfunctional mitochondria through interactions at the permeability transition pore (mPTP). Recently published clinical studies support the therapeutic rationale for mitochondria-targeted drugs in neurology (Alzheimer’s disease) and cardiology (ischemia-reperfusion injury), which Trophos is uniquely placed to exploit. Trophos was founded in 1999 by Antoine Beret and Michel Delaage, former CEO and CSO respectively of Immunotech, and has been financed by funds represented by Amundi Private Equity Funds, Turenne Capital Partenaires, Viveris Management, OTC Asset Management, Sofimac, Sofipaca, CM-CIC Capital Privé, Blue Medical Investment and the Association Française contre les Myopathies (AFM). Trophos has also received non-equity financing from the European Commission, the AFM, the Agence Nationale de Recherche and Oseo Innovation.
About Actelion Ltd

Actelion Ltd is a biopharmaceutical company with its corporate headquarters in Allschwil/Basel, Switzerland. Actelion’s first drug Tracleer®, an orally available dual endothelin receptor antagonist, has been approved as a therapy for pulmonary arterial hypertension. Actelion markets Tracleer® through its own subsidiaries in key markets worldwide, including the United States (based in South San Francisco), the European Union, Japan, Canada, Australia and Switzerland. Actelion, founded in late 1997, is a leading player in innovative science related to the endothelium -the single layer of cells separating every blood vessel from the blood stream. Actelion’s over 2,300 employees focus on the discovery, development and marketing of innovative drugs for significant unmet medical needs. Actelion shares are traded on the SIX Swiss Exchange (ticker symbol: ATLN) as part of the Swiss blue-chip index SMI (Swiss Market Index SMI®).
For further information please contact

For Actelion Ltd:
Roland Haefeli
Vice President, Head of Investor Relations & Public Affairs
Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123 Allschwil
+41 61 565 62 62 begin_of_the_skype_highlighting +41 61 565 62 62 end_of_the_skype_highlighting
+1 650 624 69 36 begin_of_the_skype_highlighting +1 650 624 69 36 end_of_the_skype_highlighting

http://www.actelion.com

For Trophos SA:
Andrew Lloyd & Associates
Andrew Lloyd / Cécilia Derrien
Tel: +33 1 56 54 07 00 begin_of_the_skype_highlighting +33 1 56 54 07 00 end_of_the_skype_highlighting
allo@ala.com / cecilia@ala.com

http://www.trophos.com

Nine U.S. Health Research Centers to Receive $255 Million

Nine health research centers have received funds to develop ways to reduce the time it takes for clinical research to become treatments for patients. The funds were awarded as part of the Clinical and Translational Science Awards (CTSA) program which is led by the National Center for Research Resources (NCRR), part of the National Institutes of Health.

“A critical goal of biomedical research is to transform discoveries into preventions, treatments, and cures,” said NIH Director Francis S. Collins, M.D., Ph.D. By working together, CTSAs are removing barriers to research, training new generations of clinical and laboratory research teams, and providing them with the equipment and resources they need.

Now in its fourth year, the CTSA consortium has generated resources that transform the research and training environment to enhance the efficiency and quality of clinical and translational research. Examples include a Web-based national recruitment registry that connects researchers with volunteers interested in participating in clinical studies, establishing public-private partnerships, and a portal that connects researchers with potential investigational drugs that may be useful in new ways.

The 2010 CTSAs expand consortium representation in new areas including New Mexico, Virginia and the District of Columbia, growing the consortium to 55 member institutions. The nine new institutions are:

Children’s National Medical Center, Washington, D.C.
Georgetown University with Howard University, Washington, D.C.
Medical College of Wisconsin, Milwaukee
University of California, Irvine
University of California, San Diego
University of Massachusetts, Worcester
University of New Mexico Health Sciences Center, Albuquerque
University of Southern California, Los Angeles
Virginia Commonwealth University, Richmond

View descriptions of these CTSA awardees at www.ncrr.nih.gov/ctsa2010.

“The nine institutions that have received CTSAs this year extend the geographic reach of the consortium and bring additional talent and expertise in such areas as children’s health, outreach to underrepresented communities, and systems to share research information,” said NCRR Director Barbara Alving, M.D.

The CTSA consortium now includes awardees in 28 states and the District of Columbia. When the program is fully implemented in 2011, it will support approximately 60 CTSAs across the nation.

A sixth and final funding opportunity announcement for CTSAs is available, calling for the next round of applications to be submitted by Oct. 14, 2010, with the awards expected in July 2011. For more information about this funding announcement, see www.ncrr.nih.gov/crfunding.

For more information about the CTSA program, visit www.ncrr.nih.gov/ctsa. The CTSA consortium website, which provides information on the consortium, current members and new grantees, can be accessed at www.CTSAweb.org.

The National Center for Research Resources (NCRR), a part of NIH, provides laboratory scientists and clinical researchers with the resources and training they need to understand, detect, treat and prevent a wide range of diseases. NCRR supports all aspects of translational and clinical research, connecting researchers, patients and communities across the nation. For more information, visit www.ncrr.nih.gov.

The National Institutes of Health (NIH)  The Nation’s Medical Research Agency  includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

BioFocus and University of Bristol enter drug discovery collaboration in chronic pain

Saffron Walden and Bristol, UK; 16 July 2010 – BioFocus and the University of Bristol today announced a new drug discovery collaboration aimed at developing treatments for chronic pain associated with diabetes (diabetic neuropathic pain).  BioFocus will provide hit-to-lead and lead optimization services for a Wellcome Trust funded program at the University of Bristol.  Total contract value for BioFocus could exceed €3.3 million in research fees over two years.

This work is supported by a Seeding Drug Discovery Award from the Wellcome Trust, to a team of researchers led by David Wynick, Professor of Molecular Medicine at the University of Bristol. The project aims to develop a new analgesic drug based on the protein galanin, a small protein that has been shown to reduce neuropathic pain in a number of models of diseases, including diabetes.  In earlier studies, several compounds from the BioFocus screening collection were shown to amplify the therapeutic effect of galanin in vitro.  In the two-year collaboration announced today, BioFocus will provide medicinal chemistry, biology and ADME/PK for this research project, with the goal to optimize these molecules for the treatment of diabetic neuropathic pain.

“This latest collaboration with the University of Bristol is a prime example of BioFocus’ ability to deliver results and thereby retain partners.  Once again we see the BioFocus screening libraries deliver promising hits that are of interest to the academic and pharmaceutical communities,” said Onno van de Stolpe, CEO of Galapagos, BioFocus’ parent company.  “We are pleased that the University of Bristol has expanded and extended this successful relationship into other strong areas of BioFocus expertise.”

“Molecules from the BioFocus collection have shown promise in amplifying the therapeutic properties of galanin in models of neuropathic pain,” said Prof. David Wynick from the University of Bristol.  “In this new collaboration with BioFocus, we aim to further optimize these molecules into potential clinical candidates for the treatment of chronic pain associated with diseases such as diabetes.”

Rick Davis, Business Development Manager at the Wellcome Trust, commented “Existing painkillers can prove largely ineffective against neuropathic pain so we are pleased to support this project, which addresses an area of huge unmet clinical need.”

About diabetic neuropathic pain
Diabetes is the most common cause of neuropathic pain, which is often experienced as a burning or electrical pain.  Existing painkillers have proven largely ineffective in treating diabetic neuropathic pain, which is believed to be caused by damaged nerves as a result of exposure to toxins or inadequate blood supply.  The World Diabetes Foundation predicts that the population of diabetes sufferers will increase from 285 million in 2010 to 438 million by 2030, given the increasing levels of obesity.

About the University of Bristol
The University of Bristol is one of the leading research universities in the UK, having an excellent national and international reputation in research, teaching and global discovery. The University is committed to combining its excellence in research and innovation with a vibrant enterprise culture and is working with government, industry and other partner organisations to encourage the growth of knowledge-based business in South West England.  More info at: www.bris.ac.uk

About the Wellcome Trust
The Wellcome Trust is a global charity dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.  More info at: www.wellcome.ac.uk

About BioFocus
BioFocus aims to expand its partners’ drug pipelines by accelerating the gene-to-drug candidate discovery process.  This is achieved through a comprehensive discovery platform, which includes target discovery in human primary cells, focused as well as diverse compound libraries, in vitro and cell-based screening, structural biology, medicinal chemistry, ADME/PK services, supported by unique chemogenomic and informatics tools, and compound library acquisition, storage and distribution services.  As a service division of Galapagos, BioFocus has over 250 employees based in the UK, the US and Switzerland.  More info at: www.biofocus.com

BioFocus® is a trademarks of Galapagos NV and/or its affiliates © Copyright 2010 Galapagos NV.

source: biofocus.com

NIH Prolongs Compound-Management Arrangement with Galapagos Until End of 2012

NIH has extended its agreement with Galapagos’ service division, BioFocus, for the operation of the Molecular Libraries Small Molecule Repository (MLSMR) through December 2012. Galapagos will thus be eligible to receive up to $8.6 million over the course of the two-year extension. The NIH MLSMR collects samples for high-throughput biological screening and distributes them to the NIH Molecular Libraries Screening Center Network. The project is funded in whole with U.S. federal funds from the NIH and HHS. BioFocus has a compound-management facility in South San Francisco that has been home to the MLSMR since 2004. The facility runs out of BioFocus’ subsidiary, Compound Focus, and stores compounds under an NIH contract for a number of industrial and U.S. government customers. Compound Focus is also in charge of distributing these compounds for high-throughput biological screening throughout the NIH’s academic network in the U.S. “BioFocus has proven that it consistently delivers high-quality service across the vast NIH screening center network,” says Onno van de Stolpe, CEO of Galapagos.

source: genengnews.com

Aquapharm and AMRI Enter into a Novel Marine Chemistry Collaboration

Aquapharm Biodiscovery, a leading marine biotechnology company, announced today it has signed a research agreement with Albany Molecular Research  to identify novel drug-like compounds and scaffolds with anti-microbial and anti-inflammatory activity from Aquapharm’s marine natural products library derived from its extensive collection of marine micro-organisms.Under the terms of this agreement, drawing on its substantial experience and expertise from previous screening campaigns with its terrestrial natural products library, AMRI will screen Aquapharm’s library against Gram-negative and Gram-positive bacteria and an undisclosed anti-inflammatory target and will isolate and elucidate the structures of novel hits. Aquapharm retains all rights to compounds resulting from the collaboration.

The collaboration represents a major step-forward for Aquapharm in realising the potential of its unique marine assets and expertise in the Pharmaceutical sector. This builds on its established deals with Croda to develop novel bio-active ingredients for the Personal Care industry and Dr Reddy’s to develop bio-catalysts, thus maximising the exploitation of the marine collection in producing a broad and diverse chemical library.

On signing of the agreement, Aquapharm CEO Simon Best said “We are confident that this collaboration will exploit the novelty, diversity and drug-like characteristics of the compounds which we know from pilot studies are abundantly produced by marine micro-organisms. These represent a virtually untapped source of compounds and scaffolds with many attractive characteristics to form the basis of numerous drug-discovery partnerships.”

“We have a wealth of experience accumulated from developing and mining our own extensive terrestrial natural product library, and we are pleased to apply this experience to Aquapharm’s marine derived library. It’s a new and exciting opportunity” said AMRI Vice President, Discovery Research and Development Bruce Sargent, Ph.D.

Initial results from this research agreement are expected during 2011. AMRI has broad screening capabilities and moreover particular expertise in seeking antibacterial natural products, having successfully completed its own internal screen of its collections yielding multiple lead compounds effective against MRSA and E.Coli organisms.

Notes to Editors

About Aquapharm Biodiscovery Ltd — www.aquapharm.co.uk

Aquapharm is a leading marine biotechnology company pioneering the discovery, isolation and development of novel, marine-derived bioactives for application in a wide range of commercial sectors, including pharmaceuticals, functional ingredients and industrial biotechnology.

Aquapharm has built a substantial and specialised collection of marine bacteria and fungi from a variety of diverse habitats. Through the application of its proprietary technologies to this collection, the company has been able to stimulate the production of novel, biologically active products with broad chemical diversity. To accelerate its discovery efforts, Aquapharm is currently focused on completing one of the world’s largest marine derived compound libraries containing small molecule and peptide compounds. The completion of this new compound library will accelerate Aquapharm’s drug discovery efforts, principally in the anti-microbial and anti-inflammatory fields. Aquapharm has commercial agreements with Croda Plc and Dr Reddy’s Laboratories in regards to sourcing marine compounds for use in the personal care and bio-catalysis fields respectively. In March 2010, Aquapharm received a GBP 4.2 million investment from existing investors and appointed biotech entrepreneur Simon Best as CEO, the company’s founder Dr Andrew Mearns Spragg as CTO and Dr Tim Morley as CSO. Aquapharm is based at the European Centre for Marine Biotechnology in Oban, Scotland.

About AMRI – www.amriglobal.com

Founded in 1991, Albany Molecular Research, Inc. provides scientific services, products and technologies focused on improving the quality of life. AMRI works on drug discovery and development projects and conducts manufacturing of active ingredients and pharmaceutical intermediates for many of the world’s leading healthcare companies. As an additional value added service to its customers, the company is also investing in R&D in order to expand its contract services and to identify novel early stage drug candidates with the goal to out-license to a strategic partner. With locations in the United States, Europe, and Asia, AMRI provides customers with a wide range of services, technologies and cost models.

SOURCE: Aquapharm Biodiscovery

Volatile Organic Compounds (VOCs) on the Gulf Coastline

Resource: EPA – United States Environmental Protection Agency

Volatile Organic Compounds (VOCs) on the Gulf Coastline

EPA is analyzing air samples for volatile organic compounds (VOCs) – including specifically, benzene, ethylbenzene, toluene, and xylene. EPA is sampling for these pollutants because they are present in oil and because, at elevated concentrations, they may cause health problems, including cancer.

These chemicals are also emitted by many other sources, such as motor vehicles, industries, and paints or solvents. The monitors cannot determine where the VOCs originate. Therefore VOC levels in the air around the monitors could be coming from the oil spill or from other sources.

To evaluate the VOCs EPA scientists compare air sampling results to health-based screening concentrations (also called “screening levels”) in the Gulf region. These screening levels are developed from health effects information about each VOC, including information regarding exposure levels that might pose an increased risk of health problems. At this time, EPA is using health-protective screening levels that assume a person is breathing a pollutant continuously  (24 hours a day, seven days a week) for as long as one year. EPA will re-evaluate this time-period if needed.

How EPA is using sampling data and screening levels for the VOCs

Monitoring staff are taking air samples at several locations along the Gulf coast. The air quality samples are collected in canisters, which are shipped to a laboratory for analysis.  The daily results shown in the table are the average 24-hour concentration for each day.

EPA will compare individual measurements as well as long-term average (i.e. levels averaged over many days) to the screening level.  Since the screening levels are based on exposure lasting for many months, this average is more appropriate for evaluating the potential risk to health than any single measurement.  But also screening the individual measurements allows EPA to closely track the results.

Results that are below the health-based screening level generally indicate a low potential for health concerns for exposures up to a year.  In addition, a single daily reading that is higher than the screening level does not indicate a health problem will occur.

However, if a measured concentration is above the health-based screening level, EPA will investigate further:

  • EPA would look at how high the concentration is above the screening level, how long the concentration stays above the screening level, and the impact of the concentration on the running average concentration over many days.
  • EPA will also look at how these measurements compare to measurements in the region prior to the spill. EPA would also look at information for that chemical, and the situations in which it might cause health problems.
  • After this further investigation, EPA would determine whether follow-up actions are needed.
  • Possible follow-up actions include conducting additional monitoring to better identify the source of the pollutant, or to track the pollutant concentration over time.
  • If there is cause for immediate concern, EPA will work with state and local officials to notify people in the area through local news media.

source: gulfofmexicohealth.com