Researchers launched a unique collaboration aimed at getting cancer drugs to the market more quickly on Wednesday — one in which three companies will cooperate with government and non-profit groups to test five experimental breast cancer drugs.

The study, called Investigation of Serial Studies to Predict your Therapeutic Response with Imaging and Molecular Analysis, or I-SPY2, will aim to use DNA to match the best drug to each individual patient, and to more quickly toss out approaches that do not work or that are too toxic.

The launch of the $26 million, five-year experiment will be announced at 9 a.m. EDT (1300 GMT) in Washingther.

Unusually, the companies agreed to share information on using genes to predict how well a patient will respond as part of the Biomarkers Consortium, which includes the U.S. Food and Drug Administration and the National Institutes of Health.

“I think it is the theme for the future of research,” Anna Barker, deputy director of the National Cancer Institute, said in a telephone interview.

“I-SPY 2 will provide a path to personalized medicine,” said Dr. Laura Esserman, a breast cancer surgeon at the University of California San Francisco who will help lead the clinical trials.

The trial will match patients to one of five experimental drugs:

– ABT-888 or veliparib, being developed by Abbott Laboratories. The pill is a PARP inhibitor, which blocks a cell repair enzyme used by cancer cells.

– AMG 655 or conatumumab, a targeted drug being developed by Amgen. It is an APO/TRAIL inhibitor that causes cancer cells to self-destruct.

– Amgen’s AMG 386, an angiogenesis inhibitor that stops tumors from growing blood vessels to nourish themselves.

– CP-751,871 or figitumumab, being developed by Pfizer Inc. to target the insulin growth factor receptor or IGFR.

– Pfizer’s HKI-272 or neratinib, another targeted therapy called a Pan ErbB inhibitor that targets several related receptors used by cancer cells.

EARLY TREATMENT

“It is the best combination I have seen of state-of-the art biomarkers and state-of-the-art drugs that enable us to put drugs into patients and start evaluating them on a faster basis,” Barker said.

“It’ll speed up the whole process.”

Patients at 20 cancer centers will be tested right after they get tiny samples of tissue taken called biopsies. Before they ever get surgery, they will be treated with one of the drugs to see if this helps prevent tumor spread.

Up to 12 different cancer drugs will be tested. Unusually, the group has FDA approval to drop and add drugs throughout the course of the trial without having to stop the trial to write a whole new protocol.

Safeway Inc. is paying for a large part of experiment. Johnson & Johnson, Roche AG subsidiary Genentech and Eli Lilly and Co. will also provide funding.

“This approach could apply to other diseases and other cancer,” said Barker.

UCSF Chancellor Dr. Sue Desmond-Hellmann said the approach could save the U.S. healthcare system money.

“It has the opportunity to make clinical trials more efficient so we will spend less to develop new remedies,” Desmond-Hellmann, a former drug company executive, said in a telephone interview.

“I predict that companies will be watching this.”

More information is available at www.biomarkersconsortium.org.

Source: Reuters

Popularity: 1% [?]

Two studies published on Wednesday show it is possible to sequence the entire gene maps of families with inherited diseases and pinpoint the offending bit of DNA.

The studies, which would not have been possible a year or two ago, are the first real delivery of the promised transformation of medical science from the Human Genome Project’s mapping of the human genetic code.

One was also made possible by some of the $5 billion that U.S. President Barack Obama directed to the National Institutes of Health in September from the $787 billion economic stimulus package.

And in that study, the genetic researcher was himself one of the patients.

Dr. James Lupski of the Baylor College of Medicine in Houston has a recessive genetic disease called Charcot-Marie-Tooth syndrome. It affects the nerves stretching from the spinal cord to the arms, legs and feet.

Lupski has been experimenting on himself and his own family for years.

“We tried every other method for 25 years to find out which mutation was important,” he said in a telephone interview.

“With this methodology we were able to do it. This is the first time whole genome sequencing has applied to actually find the cause of a disease.”

Lupski had been taking blood samples from his grandparents, parents and siblings for years. He got close but the research was considered too risky for funding by the National Institutes of Health.

“He was only able to complete this study because of the stimulus money that we got,” said Dr. Story Landis, director of the National Institute of Neurological Disorders and Stroke.

Her institute designated Lupski’s project for about half a million dollars of the money that Obama directed to the NIH.

RECESSIVE GENES

Lupski’s team used a gene sequencer from Carlsbad, California-based Life Technologies to read the entire DNA code in the samples from Lupski and three of his siblings who have the syndrome, his parents and four other siblings who do not.

“It is a recessive disease and neither of my parents have the disease. Each of us who has it got one mutant allele (gene) from my mom and one mutant allele from my dad,” he said.

Researchers know about 40 different genes that can cause Charcot-Marie-Tooth. But in each family, only one of these genes is involved.

The sequencing revealed a gene called SH3TC2, the researchers reported in the New England Journal of Medicine. Other groups are already working on a drug that may affect that gene, Lupski said.

The researchers also found that family members who inherited just one faulty copy of the gene had a predisposition to carpal tunnel syndrome, in which a nerve in the wrist can get pinched.

As prices are coming down on the cost of sequencing a human genome, more such research will be possible.

“We estimate that the entire effort would currently cost less than $50,000,” the researchers wrote.

In a second study, Jared Roach of the Institute for Systems Biology in Seattle and colleagues sequenced the entire genomes of a family of four affected by two recessive genetic diseases — Miller syndrome, which can cause facial disfigurement, and primary ciliary dyskinesia, a lung disorder that raises the risk of respiratory infections because the hairlike extension on cells called cilia fail to move properly.

“Our results demonstrate the unique value of complete genome sequencing in families,” they wrote in the journal Science.

They used a sequencer made by another one of the companies exploiting genomic sequencing, Complete Genomics based in Mountain View, California.

Source: Reuters

Popularity: 1% [?]

A group of doctors have confirmed that 12-lipoxygenase (12-LO) is indeed found in human islets and that its pro-inflammatory lipid products can lead to lower insulin production and beta-cell death, which gives rise to type 1 diabetes. The team, from Eastern Virginia Medical School’s (EVMS) Strelitz Diabetes Center, studied human islets from individuals who had donated their bodies to science through the Juvenile Diabetes Research Foundation (JDRF) Islet Resource Center Consortium.

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The research was led by Jerry Nadler, M.D., professor and chair of internal medicine and director of the center. It is published in the February issue of The Journal of Clinical Endocrinology and Metabolism.

Prior research has established that 12-LO, a protein-based enzyme found in beta cells, produces specific lipids that cause inflammation and can lead to the death of beta cells in laboratory models. Yet, little is known about the differential effect of the various hydroxyeicosatetraenoic acids (HETEs) that result from LO activity in human islets, the EVMS team explains. Their study thus focused on comparing the effects of 12-LO products on human islet viability and function.

One challenge has been to validate that 12-LO and its pro-inflammatory lipid products have a role in human diabetes. Gaining access to human beta cells can be difficult, but the school was able to leverage resources from JDRF’s Islet Resource Center Consortium, Dr. Nadler explains.

Human islets were treated with stable compounds derived from LOs: 12(S)-HETE, 15HETE, 12HPETE, and 12RHETE. The islets were then examined for insulin secretion and islet viability. The p38-MAPK and JNK stress-activated pathways were investigated as mechanisms of 12-LO-mediated islet inhibition in rodent and human islets.

They found that insulin secretion was consistently reduced by 12(S)-HETE and 12HPETE. 12(S)-HETE at 1 nM reduced viability activity by 32% and increased cell death by 50% at 100 nM in human islets. These effects were partially reversed with lisofylline, a small molecule anti-inflammatory compound that protects mitochondrial function.

Additionally, 12(S)-HETE increased phosphorylated p38-MAPK protein activity in human islets, the scientists report. Injecting 12-LO siRNA into C57BL/6 mice reduced 12-LO and phosphorylated p38-MAPK protein levels in mouse islets. The addition of pro-inflammatory cytokines increased phosphorylated p38 levels in normal mouse islets but not in siRNA-treated islets.

“We are currently working with investigators in California and the National Institutes of Health to identify ideal medications that would target 12-LO as a new treatment to halt immune damage to human insulin-producing cells,” says David A. Taylor-Fishwick, Ph.D., associate professor.

Source: GEN News

Popularity: 2% [?]

A study in mice suggests using cellphones may help prevent some of the brain-wasting effects of Alzheimer’s disease, U.S. researchers said on Wednesday.

After long-term exposure to electromagnetic waves such as those used in cell phones, mice genetically altered to develop Alzheimer’s performed as well on memory and thinking skill tests as healthy mice, the researchers wrote in the Journal of Alzheimer’s Disease.

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The results were a major surprise and open the possibility of developing a noninvasive, drug-free treatment for Alzheimer’s, said lead author Gary Arendash of the University of South Florida.

He said he had expected cell phone exposure to increase the effects of dementia.

“Quite to the contrary, those mice were protected if the cell phone exposure was stared in early adulthood. Or if the cellphone exposure was started after they were already memory- impaired, it reversed that impairment,” Arendash said in a telephone interview.

Arendash’s team exposed the mice to electromagnetic waves equivalent to those emitted by a cellphone pressed against a human head for two hours daily over seven to nine months.

At the end of that time, they found cellphone exposure erased a build-up of beta amyloid, a protein that serves as a hallmark of Alzheimer’s disease.

The Alzheimer’s mice showed improvement and had reversal of their brain pathology, he said.

“It (the electromagnetic wave) prevents the aggregation of that bad protein of the brain,” Arendash said. “The findings are intriguing to us because they open up a whole new field in neuroscience, we believe, which is the long-term effects of electromagnetic fields on memory.”

Arendash said his team was modifying the experiment to see if they could produce faster results and begin testing humans.

Despite decades of research, there are few effective treatments and no cure for Alzheimer’s, the most common form of dementia. Many treatments that have shown promise in mice have had little effect on humans.

More than 35 million people globally will suffer from Alzheimer’s disease or other forms of dementia in 2010, according to the Alzheimer’s Association.

There has been recent controversy about whether electromagnetic waves from cellphones cause brain cancer.

Co-author Chuanhai Cao said the mice study is more evidence that long-term cellphone use is not harmful to the brain.

Groups such as the World Health Organization, the American Cancer Society, and the National Institutes of Health, have all concluded that scientific evidence to date does not support any adverse health effects associated with the use of cellphones.

Source: Reuters

Popularity: 3% [?]

Oh, what a tangled web. Drugmakers, doctors, ghostwriters, academic researchers, medical schools, CME providers … they’re all linked together by industry money and influence. At least that’s the view of 100 medical ethicists, researchers, professors, patient advocates, et al., who are asking the National Institutes of Health to fund studies about conflicts of interest and their effects on patient care. And these aren’t fringe characters; some big-name individuals and institutions signed.

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“There is growing evidence that each strand of this web is compromised by ethical lapses and financial conflicts of interest,” states the group’s letter to NIH chief Francis Collins. There’s a growing backlash against the relationships themselves, justified or not. State legislators have banned gifts from drugmakers to doctors. Some medical schools have barred drug reps who don’t have appointments; some have even stopped taking free drug samples. And last but not least, Congress has launched one probe after another, examining the financial ties that bind those who make the drugs to those who prescribe them.

Drugmakers have been scrambling to get ahead of the public opinion curve by voluntarily disclosing financial relationships with doctors, cutting off funding to private CME firms, and capping speaker fees and consulting payments to individual doctors. But the lapses continue to surface.

“To what extent have ghostwritten articles corrupted the medical and scientific literature?” the letter asks, going on to demand that NIH acknowledge that it just doesn’t know if–or how much–financial relationships end up influencing actual medical decision making. And then, of course, address that gap in knowledge by launching some government-funded studies. The letter asks for a face-to-face meeting. We’ll have to wait and see whether that comes to pass.

Source: FiercePharma

Popularity: 2% [?]

A trial examining the use of Pfizer’s Revatio (sildenafil) to treat pulmonary hypertension in patients with sickle cell disease was stopped early due to safety concerns, The National Institutes of Health reported Tuesday. The NIH explained that an interim review of safety data from 33 patients led to a halt in the trial nearly a year ahead of schedule after findings showed a significantly higher risk for serious medical problems in those who took Revatio, compared with those who took placebo.

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The patients, who had sickle cell disease and mild-to-severe pulmonary hypertension when they enrolled in the randomised trial, had completed 16 weeks of treatment with either Revatio or placebo. The preliminary data showed that 38 percent of those who took Pfizer’s drug had serious adverse events, compared with 8 percent of those who received placebo. The most common medical problem identified in the review was episodes of severe pain known as sickle cell crises, and the NIH stated that Revatio has not been linked to deaths in the trial.

Elizabeth Nabel, the director of the NIH’s National Heart, Lung and Blood Institute, stated that the medical problems seen in the study were related specifically to sickle cell disease, adding that researchers are examining the possible causes of the early findings.

Source: FirstWord

Popularity: 3% [?]

US President Barack Obama will nominate Francis Collins to lead the National Institutes of Health. Collins was head of the NIH’s National Human Genome Research Institute until he stepped down last year.

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Commenting on the nomination, American Heart Association President Clyde Yancy stated that Collins’ real advantage “is the ability to translate deep and complex science to the lay population…in a meaningful way that allows it to be tangible and actionable.”

Source: FirstWord

Popularity: 2% [?]

The Obama administration today issued final guidelines regarding use of stem cells for research purposes and in the process, it announced rules expected to make even more stem cells available for lab work.

In a draft of the guidelines outlined by the National Institutes of Health in April, only stem cells from excess embryos at fertility clinics that would otherwise have been discarded and that had received donor consent were to be eligible for federal funding. In the final guidelines, stem lines developed before the guidelines go into effect tomorrow won’t be asked to show that they were derived from the specific ethical requirements set forth in the guidelines, according to the Washington Post.

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Instead, older stem cell lines that were derived in the spirit of the ethical principles could qualify for federal money, potentially making more cell lines eligible for research purposes.

“I expect that most existing lines will be found to have been ethically derived,” Sean Morrison, director of the University of Michigan Center for Stem Cell Biology, told the Associated Press. “This will eventually make hundreds of new stem cell lines available for use.”

Acting NIH Director Raynard Kington told reporters today: “We think this is a reasonable compromise to achieve the president’s goal of both advancing science while maintaining rigorous ethical standards. We believe that judgment is necessary.”

Source: The Wall Street Journal

Popularity: 3% [?]

Amid much discussion around comparative effectiveness of medical treatments and whether cost should be a factor in treatment decisions, a new article in the Journal of the National Cancer Institute estimates it would cost $440 billion to extend life by one year for the 550,000 Americans who die annually of cancer, reports the WSJ.

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The authors, from the National Cancer Institute and National Institutes of Health, say that 90% of cancer drugs approved in the past four years cost more than $20,000 for 12 weeks worth of treatment.

Some drugs have limited upsides, and these shouldn’t be developed unless they will cost patients less than $20,000 for a standard course, they say. Two more recommendations from the authors: doctors shouldn’t prescribe cancer medicines for non-approved purposes, and new medicines with marginal benefits shouldn’t be used for those with advanced cancer.

Treating lung-cancer with Erbitux, a Bristol-Myers and Eli Lilly drug, costs $80,000 for an 18-week regimen but extends life by only 1.2 months, the authors estimate. Bristol-Myers says the real-world cost number of Erbitux is closer to $10,000 a month. Drug makers say the cost estimates are often exaggerated because most patients are only on them for limited amounts of time and many received financial assistance, according to the WSJ.

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So the challenge is this: How to develop new medicines — especially those that might help certain individuals a lot even if the benefit to patients as a group isn’t impressive — while trying to keep costs in check.

“We can’t add on Mercedes-like drugs one after another and have every single patient cost the system phenomenal amounts of money,” Eric Winer, chief scientific adviser to Susan G. Komen for the Cure, a breast-cancer advocacy group, told the WSJ. “But we have to be careful not to slow down the process of drug development. Ultimately it is medical therapy that will make a huge difference in people’s lives.”

Source: The Wall Street Journal

Popularity: 3% [?]

Bloomberg reported Tuesday that a US district court judge ruled for the dismissal of a whistleblower lawsuit alleging that Pfizer sought to increase sales of Lipitor (atorvastatin) by urging physicians to prescribe the drug for off-label use in patients with “moderate” raised cholesterol levels. Judge Edward Korman commented that the defendant “has not identified any false claims or physicians who were induced to write a prescription for an off-label use.”

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Korman added that the essence of the claim by Jesse Polansky, a former director of outcomes management strategies for the drugmaker, “is that Pfizer advocated that Lipitor be prescribed in cases in which its use was not recommended by the guidelines…This is insufficient.” The judge noted that guidelines from the National Institutes of Health recommend that patients with moderately high cholesterol levels first try lifestyle changes to improve their cholesterol measures.

The court ruled that Polansky can re-plead his complaint, which was originally filed in 2004.

Source: FirstWord

Popularity: 2% [?]