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Virus Hunter Discovers Origin of Malaria in Chimps

CNN.com, August 4, 2009  —  Nathan Wolfe is a hunter, but he doesn’t carry a gun. His prey are invisible to the naked eye.

Wolfe leads expeditions into the mysterious world of viruses and pathogens.

“They are everywhere,” said Wolfe, a microbiologist who speaks of his targets — infectious organisms — with the giddy lilt of a teenager on a first date. “We have the potential to explore a completely new biological world and go out and really find new things all the time.”

One bug has been Wolfe’s singular obsession for more than a decade, arguably the biggest menace to humans: malaria.

“If you think about HIV virus as a singular hurricane event, malaria is like the hurricane that’s been hitting for thousands of years — constantly,” said Wolfe, who heads a research institute called the Global Viral Forecasting Initiative.

Although scientists have amassed volumes of knowledge about this nimble and changeable parasite, none of that knowledge has reaped a malaria vaccine or a sustainable ability to fight it.

But Wolfe believes that a discovery by his team may have tipped the balance in humans’ favor.

Monday, research by Wolfe and his colleagues appeared in the journal Proceedings of the National Academy of Sciences, outlining what they believe to be the origins of malaria.

According to Wolfe and his team, malaria jumped to humans from our closest ancestors: chimpanzees. This finding, he says, unlocks one of the biggest medical mysteries confronting humans.

“We can actually understand, we can actually re-create the story that explains a fundamental and important part of our history,” Wolfe said. “For me, this is the microbiological equivalent of discovering the origins of HIV.”

Understanding the origin — and the genetic behavior — of a pathogen is the holy grail in the world of infectious disease.

Though not a public health issue in the United States, malaria infects 500 million people every year and kills between 1 million and 3 million. Its assault on humans has been relentless, especially among African children.

Malaria hijacks and kills healthy red blood cells and infects the liver. If not treated soon after onset of symptoms — such as fever, chills, diarrhea and shortness of breath — those infected by malaria can have neurological problems or cognitive problems, or ultimately die.

It is a biological menace, constantly morphing, eluding the best efforts to fight it.

“The lack of an effective malaria vaccine is one of the biggest public health failures of our time,” Wolfe said.

From Wolfe’s perspective, the best way to reverse those failures, and to create a vaccine, is to first understand the genetics of the disease.

His understanding grew on one of several trips to the dense forests in Cameroon. He collaborated with a team of pathogen hunters, including Fabian Leendertz of the Robert Koch Institute in Germany and Stephen Rich of the Laboratory of Medical Zoology at the University of Massachusetts, Amherst. They studied chimpanzees at the Limbe Wildlife Center in the Ivory Coast.

Why look at chimpanzees?

“They are our closest ancestors,” Wolfe said. “The closer two animals are, the higher the chances they will be able to share diseases and the more likely one of the viruses will jump to us.”

Wolfe has not confirmed when it happened, but he believes that malaria’s jump from chimpanzees to humans occurred thousands of years ago — maybe more. The conduit from infected chimpanzees to humans was most likely the mosquito, a common malaria carrier even today.

“This fills out a big blank space,” Wolfe said. “But at the same time, this finding also suggests there is a lot that we don’t know. The real life world of malaria is something we know very little about.

“As a scientist, the bigger the mystery, the better,” he said.

But it wasn’t just about mystery. Wolfe also had a personal score to settle. He has been infected three times by malaria. One time it almost killed him.

It was an experience that strengthened his resolve to fight this disease.

Five years after his brush with death, Wolfe was back in Cameroon at Mfou National Park. Mfou is also a sanctuary for orphaned animals, including chimpanzees.

Wolfe and colleagues tested the blood of 84 chimpanzees at Mfou and 10 chimpanzees in the Ivory Coast, all in captivity and all infected with malaria.

Next, the scientists teased out the genetic structure — the DNA — of the chimpanzee malaria and compared it with the DNA structure of human malaria.

The chimpanzee malaria, called plasmodium reichenowi, was genetically similar to the strain killing humans globally, plasmodium falciparum. But the chimpanzee strain is older, or what infectious disease experts would call more diverse.

That genetic similarity, and the suggestion that the chimpanzee malaria DNA is older than human DNA, is solid proof for Wolfe and his team that malaria jumped from chimpanzees to humans.

“It jumped over just like SARS did, just like avian flu did, just like HIV did,” Wolfe said. “What is really crucial, what is significant, is it continuing to jump over?”

If malaria is continuing to jump over, and if it is genetically more complex than previously thought, then, according to Wolfe, the eight novel malaria parasites his team found add chapters to the story about malaria and potentially widen the scope for creating an effective vaccine.

Malaria experts are impressed with the finding, but not all are convinced that this discovery will cause the vaccine research field to explode.

“This is an interesting biological observation that may or may not have human implications,” said Dr. Kent Campbell, director of the malaria program at PATH, a leading global health organization unaffiliated with Wolfe. “Malaria is a very finely evolved organism that has proven to be quite resistant to classic vaccine research. To call this a major breakthrough on making an effective vaccine might be a bit optimistic at this point in time.”

Another malaria expert is only slightly more optimistic.

“The idea that all of this misery in the world could have been due to a single event of the distant past is striking,” said Dr. Patrick E. Duffy, director of the malaria program at the Seattle Biomedical Research Institute. “What it reminds us is that the human species remains always at risk for introduction of new infectious agents.”

Wolfe is undaunted.

“In terms of implications for vaccines, I don’t know that it tells us that much.

“When you’re developing treatment and vaccine strategies, you need to know what it is in the population that you need to vaccinate against,” he said. “We’re just beginning to describe this iceberg. We know a lot of it’s underwater. We know a lot of it is unknown. I think that is part of the excitement, scientifically, for those of us who are out there trying to discover these things.”

Could those strains could change the landscape, give new information, make a malaria vaccine possible? Could those strains change the strategy by which we fight all potential pandemics?

Wolfe thinks so.

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By Rob Christensen, Staff Writer

GoogleNews.com, NewsObserver.com, RALEIGH – President Barack Obama came to North Carolina to launch a vigorous defense of his health care proposal Wednesday, saying the option of doing nothing would result in insurance premiums doubling for most Americans over the next decade.

Saying that there has been a lot of misinformation about his proposal, Obama said keeping the current system was a prescripton for escalating health care costs, a lack of insurance for people with pre existing conditions and businesses struggling to provide health care to employees.

He said his plan was being deliberately distorted by his critics.

“Nobody is talking about some government takeover of health care,” Obama told a packed gymnasium at Broughton High School. “I’m tired of hearing that. I have been as clear as I can be. Under the reform I’ve proposed, if you like your doctor, you keep your doctor. If you like your health care plan, you keep your health care plan. These folks need to stop scaring everybody.”

Obama spoke for about an hour at what was billed as a town hall before a friendly audience of mainly supporters. About a third of his talk was a defense of his stimulus program, a third a defense of his health care plan, and a third questions from the audience.

The president took about a half dozen questions from audience members on topics such as family practice doctors, prescription drug prices and insurance costs for average Americans.

The talk was a hit with Willis Linder, 83, a retired New York City policeman living in Cary, who was glad to hear that the Obama plan would not effect his Medicare.

“I was concerned about it,” Linder said.

Obama was greeted with picketers at several locations near the school and along the motorcade route downtown. They held signs with slogans such as “ObamaCare Wrong for NC, Wrong for The USA” and “Freedom Isn’t Free, Neither Is Obamacare.”

Obama’s visit came at a time when North Carolina has been the focus of an intense lobbying campaign by both sides of the health care debate. The state is home to a number of moderate Democrats who are seen as persuadable and headquarters for some major pharmecuetical industries.

Congress was in session and none of the members joined Obama in Raleigh, including Democratic Sen. Kay Hagan, who is considered a key swing vote.

Progressives Rally to Save Public Option

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Speaker of the House Nancy Pelosi and House progressives pushed against Blue Dog Democrats. (Photo: Somodevilla / Getty)

 

Truthout.com, July/August 2009, by Matt Renner  —  The health care debate ripped the bandage from a long-festering wound in the Democratic party this week, splitting the progressives and the conservative Blue Dogs in the House of Representatives. After drawing a line in the sand on Thursday, progressive forces altered the course of the legislation, restoring a key provision.

The fallout happened when conservative Democrats and Chairman of the House Energy and Commerce Committee Henry Waxman (D-California) struck a deal to move forward on stalled health care legislation. The deal would have reduced health care subsidies for lower- and middle-class Americans while increasing the amount of money the new public health insurance system would have paid to doctors and hospitals.

Progressives objected on both fronts, saying that the increase in reimbursements would hurt the viability of a public plan and would do nothing to control costs. They insisted on keeping reimbursements at the same levels as current reimbursements under Medicare, an issue that they insisted was a deal breaker, which threatened to derail the legislation and further damage the relationship between conservative and progressive members of Congress.

A deal brokered by Waxman would restore between 50 and 65 billion dollars in subsidies to the bill, according to press reports. The deal will allow the bill to pass out of committee, a major goal of Democratic leaders, who have been trying to maintain momentum going into their summer vacation.

Democrats need to accomplish health care reform going into the 2010 elections. They will need a unified vote to pass legislation in the face of almost guaranteed unanimous Republican opposition.

Public Option Under Fire

Proposed legislation containing a so-called “public option” has been under assault by health industry allies, lobbyists with fat checkbooks, Republicans and conservative Democrats. Industry opposes the public option because it could create a competing health insurance program without the need to show a profit every quarter and with strong bargaining power over prescription drug makers.

Wednesday, eager to get a health bill passed out of all relevant committees before Washington’s mandatory summer vacation, Speaker Nancy Pelosi and Energy and Commerce Committee Chairman Henry Waxman compromised with conservative Democrats and reportedly watered down the health care bill, damaging the public option and reducing the low- and middle-class health care subsidies.

Progressive members of Congress stood strong on Thursday, vowing to block any weakened bill.

 We simply cannot vote for such a proposal,” 57 members of the Congressional Progressive Caucus (CPC) explained in a letter to Pelosi, Waxman, and other committee chairmen involved in drafting health reform.

At a press conference, California Rep. Lynn Woolsey, co-chair of the CPC, said the progressives had reached their limit. “We can compromise no more,” Woolsey said.

Health care is a central issue for the CPC. Their letter and public statements served as a warning shot to the party leadership at a critical point in the turbulent health care negotiations.

The CPC has previously come under fire for backing down; the strategic timing of this dust-up is an indication that they may be willing to risk their necks.

“Fifty [votes] is our threshold,” CPC co-chair Rep. Raul Grijalva (D-Arizona) said while drumming up support for the letter, adding, “that’ll kill anything.”

Report Says Single Payer to Get a Vote

According to Politico, citing an anonymous Democratic aide, a separate deal brokered between progressives and leadership will give progressives a big win. A floor vote will be scheduled for a bill enacting a single payer health system, a long-held goal of progressives.

Single payer would be a fully incorporated government health care organization similar to the Canadian system.

While a single-payer bill will probably not gain the support of enough members to pass, it will clearly define where members stand on an issue that then-candidate for Senate Barack Obama previously endorsed.

“I happen to be a proponent of a single-payer universal health care plan … we may not get there immediately because first we’ve got to take back the White House, we’ve got to take back the Senate, and we’ve gotta take back the House,” then State Senator Barack Obama famously said in 2003 while campaigning for his future Illinois Senate seat.

Pelosi on Offense

Speaker Pelosi is getting tougher in her confrontation with the health care industry forces, who have been engaged in an extraordinary lobbying effort to protect their profitability and total dominance of early and middle life health services.

“They are the villains in this,” Pelosi said Thursday, referring to private insurance companies. “They have been part of the problem in a major way. They are doing everything in their power to stop a public option from happening. And the public has to know that. They can disguise their arguments any way they want, but the fact is that they don’t want the competition.”

Pelosi urged fellow Democrats to “take on a big special interest that has not made our country healthier, has made costs spiral upward, and for whom that is coming to an end.”

Friday, the Democratic Congressional Campaign Committee (DCCC) announced an August media campaign targeting two dozen Republicans on the issue of health reform.

“Time and again, Republicans protect a broken system of skyrocketing costs, insurance companies making health care decisions, and record-setting insurance company profits instead of working with President Obama to bring real health insurance reform,” DCCC Chairman Chris Van Hollen (D-Maryland) said.

Congress, Blue Dogs Flush With Industry Cash

An average of $1.4 million per day has been spent on lobbying by health care interest groups in 2009, according to a report from the nonpartisan group Common Cause.

In other words, in 2009, the health care industry spent an average of $2,600 per day per member of Congress trying to influence legislation.

According to the report, health industries have contributed roughly $373 million directly to members of Congress and have spent over $3 billion on lobbying since 2000.

The Blue Dog coalition has played a central role in combating a public option and pushing the House version of health reform legislation in an industry-friendly direction. Their votes will be critical to passing legislation in the house. Blue Dogs have also been rolling in contributions from health care-connected donors.

“The typical member [median not mean for accuracy] of the Blue Dog caucus in the U.S. House of Representatives has received $10,300 more from insurers than the typical non-Blue Dog Democrat in the House (including health and accident insurers, HMOs and other health services) and only $3,625 less than the typical House Republican,” according to a report from the nonpartisan Center for Public Integrity, a group that specializes in tracking money in politics.

The Blue Dog political action committee (PAC), the fund they can use to help the campaigns of fellow conservative Democrats, has raked in over $1.1 million this year through June. Over half of these dollars came from health and financial services-linked industry according to the report.

“This is not really primarily a health care debate. It is a debate about the health care industry and the drug companies spending a huge sum of money to try to get their way,” Sen. Bernie Sanders (I-Vermont), a avid backer of public health care, recently told reporters.

»


Matt Renner is an editor and Washington reporter for Truthout. He can be reached at Matt@truthout.org.

GoogleNews.com, ScienceDaily.com,  July/August 2009  –  University of Florida researchers were able to program bone marrow stem cells to repair damaged retinas in mice, suggesting a potential treatment for one of the most common causes of vision loss in older people.

The success in repairing a damaged layer of retinal cells in mice implies that blood stem cells taken from bone marrow can be programmed to restore a variety of cells and tissues, including ones involved in cardiovascular disorders such as atherosclerosis and coronary artery disease.

“To our knowledge, this is the first report using targeted gene manipulation to specifically program an adult stem cell to become a new cell type,” said Maria B. Grant, M.D., a professor of pharmacology and therapeutics at UF’s College of Medicine. “Although we used genes, we also suggest you can do the same thing with drugs – but ultimately you would not give the drugs to the patient, you would give the drugs to their cells. Take the cells out, activate certain chemical pathways, and put the cells back into the patient.”

In a paper slated to appear in the September issue of the journal Molecular Therapy, scientists describe how they used a virus carrying a gene that gently pushed cultured adult stem cells from mice toward a fate as retinal cells. Only after the stem cells were reintroduced into the mice did they completely transform into the desired type of vision cells, apparently taking environmental cues from the damaged retinas.

After studying the cell-transformation process, scientists were able to bypass the gene manipulation step entirely and instead use chemical compounds that mirrored environmental conditions in the body, thus pointing the stem cells toward their ultimate identities as vision cells.

“First we were able to show you can overexpress a protein unique to a retinal cell type and trick the stem cell into thinking it is that kind of cell,” said Grant, who collaborated with Edward Scott, Ph.D., the director of the Program in Stem Cell Biology and Regenerative Medicine at UF’s McKnight Brain Institute. “As we proceeded, we found we could activate the stem cells by mimicking the body’s natural signaling channels with chemicals. This implies a whole new field of stem cell research that uses drug manipulation rather than genetic manipulation to send these immature cells along new pathways.”

Scientists chose to build retinal pigment epithelial cells, which form the outer barrier of the retina. In addition to being very specialized and easy to identify, RPE cells are faulty in many retinal diseases, including age-related macular degeneration, which affects nearly 2 million people in the United States, and some forms of blindness related to diabetes.

“This work applies to 85 percent of patients who have age-related macular degeneration,” Grant said. “There are no therapies for this devastating disease.”

The work was supported by the National Eye Institute. Researchers removed blood stem cells from the bone marrow of mice, modified the cells in cultures, and injected them back into the animals’ circulatory systems. From there, the stem cells were able to home in on the eye injury and become retinal cells.

At 28 days after receiving the modified stem cells, mice that had previously demonstrated no retinal function were no different than normal mice in electrical measures of their response to light.

Grant and UF have patented some technology involved in the research.

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Microscopy image of a hematopoietic stem cell (in yellow) surrounded by other cells, in a spleen section. © Frédéric Mourcin

GoogleNews.com, PhysOrg.com, July/August 2009  —  Hematopoietic stem cells are capable of manufacturing all types of blood cells. But which factors influence the production of a specific type of cell? Until now, it was thought that this was a random process. 

At the Centre d’Immunologie de Marseille-Luminy, a team of CNRS and Inserm (France) researchers led by Michael Sieweke has discovered the factors that determine the type of cells produced. The mechanism they have demonstrated in the mouse involves one factor intrinsic to the cell and one extrinsic factor. These results were published in the journal Cell on July 24, 2009. 

Stem cells are a source of much hope, thanks to their extraordinary ability to produce all types of cell in the body or an organ, depending on their origin. Scientists are now trying to understand the mechanisms that commit stem cells to a particular specialization.

At the Centre d’Immunologie de Marseille-Luminy, CNRS and INSERM researchers have been working on mouse hematopoietic stem cells. They studied the development of myeloid cells, a lineage of white blood cells that combats microorganisms by “eating” them, by releasing toxins or by alerting other specialized immune cells. Until now, it was thought that the production of different specialized cells from a hematopoietic stem cell was a random process. Sieweke’s team has discovered that in the case of myeloid cells, it is the combined action of two proteins which is relevant; one protein that is situated inside the cell (transcription factor) and the other outside (a cytokine).

Transcription factors are capable of switching genes on or off. The identity of a cell is the combination of active genes it possesses. Because of this, scientists already suspected that transcription factors played an important role in the orientation of differentiation. They also knew that blood cells can only prosper in an environment containing a particular cytokine, a type of hormone specific to each cell type. But until now, they thought that cytokines assisted the survival and renewal of cells without affecting their “fate”. The team in Marseille has now shown that a specific cytokine (M-CSF) places stem cells on a “myeloid pathway”, but that these stem cells can only follow this path if levels of a certain transcription factor (MafB) within the cells is low. These findings help to solve a mystery that has fascinated specialists during the past fifty years. In the longer term, these results may throw new light on the mechanisms of leukemia, where abnormal stem cells remain “undecided” and are still able to escape therapy.

Until now, studies on hematopoietic stem cells had opened the way to research on stem cells in other tissues. In this context, the results achieved and published by Michael Sieweke and his colleagues may provide more general information on how stem cells function (in the brain, muscle or intestine).

More information: MAFB Restricts M-CSF Dependent Myeloid Commitment Divisions of Hematopoietic Stem Cells,
Sandrine Sarrazin, Noushine Mossadegh-Keller, Taro Fukao, Athar Aziz, Frederic Mourcin, Laurent Vanhille, Louise M. Kelly-Modis, Philippe Kastner, Susan Chan, Estelle Duprez, Claas Otto and Michael H. Sieweke, Cell, 24 July 2009 .

University of Southern California, April 2009,. Mechanism That Regulates Movement Of Blood-forming Stem Cells In The Body Revealed. ScienceDaily  –  Researchers at the Keck School of Medicine of the University of Southern California (USC) have identified a signaling pathway that helps regulate the movement of blood-forming stem cells in the body-a finding that provides important new insight into how stem cells move around the body and which may lead to improvements in the efficiency of bone marrow transplants.This study appeared in the journal Nature

“By identifying the key mechanism by which these stem cells home and engraft to the bone marrow, it may be possible to pharmacologically treat the cells to activate this pathway and thus increase the effectiveness of bone marrow transplants,” says lead author Gregor Adams, Ph.D., assistant professor of cell and neurobiology at the Keck School and a researcher at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC.

Hematopoietic stem cells are blood-forming cells that circulate through the body shifting back and forth between the bloodstream and bone marrow, Adams explains. When patients receive a bone marrow transplant, healthy blood stem cells are injected into their veins. Unless those stem cells can find their way into a specific site known as the stem cell niche, they cannot develop properly to replenish the white cells, red cells and platelets in the patient’s blood.

The mechanisms that guide the cells during this migration have not been well understood. However, in this study the researchers found that blood-forming stem cells that lacked a specific signaling molecule, called GalphaS, did not home to or engraft in the bone marrow of adult mice, Adams says.

“Here we show that the GalphaS pathway is a critical intracellular pathway involved in this process,” he says. “Currently, large numbers of blood-forming stem cells are required in bone marrow transplantation due to the limited efficiency of the homing process. This study opens up the possibility of treating bone marrow cells with GalphaS pathway activators as a means to increase the effectiveness of bone marrow transplants.”

Improving the efficiency with which stem cells colonize the bone marrow following transplantation could have far-reaching implications for disease treatment, says Martin Pera, Ph.D., director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC.

“For example, such a discovery might enhance the utility of umbilical cord blood, which contains only limited numbers of stem cells, for the treatment of cancer and blood disorders in children and adults,” Pera says.

The study was funded by the National Heart, Lung & Blood Institute.

GoogleNews.com, FindPharma.com, July/August 2009, by Stephanie Sutton  —  The number of alliances between diagnostics companies and pharmaceutical companies is set to rise because of the growth of personalized medicine, according to a report from PricewaterhouseCoopers (PwC).

“We expect alliances with the pharmaceutical industry to increase in the next 2-5 years, but this will be driven by factors including the pricing of diagnostics, the extent of reimbursement coverage and the burden of any clinical validation work required for market access,” said PwC Director Loïc Kubitza in a statement about the report.

The report, Diagnostics 2009: Moving Towards Personalized Medicine, claims that the drive toward personalized medicine influenced three of the 10 largest merger and acquisition deals in 2008. In addition, four of the licensing deals by the 10 largest in vitro diagnostics companies were motivated by personalized medicine. The PwC statement also highlighted the recent deal between GlaxoSmithKline (London) and Enigma (Salisbury, UK), a UK-based diagnostics group, to develop a test that quickly diagnoses specific strains of influenza as evidence of the trend for personalized medicine.

According to PwC, the drive toward personalized medicine is caused by several factors, including regulatory agencies that are introducing requirements to test for certain biomarkers before prescribing certain drugs. More people may also now undergo genetic testing because of legislation introduced in the US and Europe last year that protects individuals from genetic discrimination.

“Pharmaceutical companies understand the contribution of biomarkers and diagnostics in improving the design and probability of success of clinical trials,” said Simon Friend, global pharmaceuticals and life sciences industry leader at PwC, also explaining that greater emphasis is now being placed on a companion biomarker test when deciding on a drug’s reimbursement. He added: “These factors will combine to accelerate the development of new diagnostics for personalized medicine. Together we anticipate that alliances and collaboration will be inevitable as the market need expands.”

Stephanie Sutton is an assistant editor at Pharmaceutical Technology Europe.

Report projects more drug-diagnostic alliances

“Companion diagnostics” trend on rise

GoogleNews.com, CHICAGO, July/August 2009 (Reuters), by Julie Steenhuysen – Better diagnostic tests and pressure to lower healthcare costs may finally usher in the era of personalized medicine, in which patients get drugs tailored to their genetic makeup, a new report suggests.

Personalized medicine has been a researcher’s dream since 2003 when scientists completed the Human Genome Project — a decade-long race to sequence all of the DNA in people.

Drug companies and regulators are now looking for tests that increase the odds a high-cost biotechnology drug will work. They are using biomarkers — such as specific proteins or genes — to design better and cheaper clinical trials, lowering the cost of drug development.

“The fruits of the Human Genome Project are finally going to give us better insights into what works, and doesn’t work for people,” said Dr. David Levy of PricewaterhouseCoopers, which released a report on Thursday predicting increasing alliances between drug and diagnostics firms.

Levy said many patients were prescribed drugs that may have no benefit at all. According to the report, the response rate to current drugs ranged from 20 to 75 percent, depending on the compound or condition.

“Potentially, we can be much more specific with respect to who should get a drug and who should not,” he said.

The report said the diagnostics market could grow 5 percent a year to $50 billion by 2012. Sales of molecular diagnostics, which include tests that analyze DNA or the chemical messenger RNA, could double to $5 billion in 2012 from $2.6 billion in 2007.

TESTS BEFOREHAND

Some of that growth is being driven by regulators.

The report noted that regulatory agencies including the U.S. Food and Drug Administration and the European Medicines Agency were now requiring the use of “companion diagnostics” — diagnostic tests patients must have before a certain medication can be prescribed.

So far, the FDA requires the use of companion diagnostic tests with Pfizer’s (PFE.N) HIV drug Selzentry or maraviroc; Bristol-Myers Squibb’s (BMY.N) Erbitux or cetuximab for colorectal cancer and its leukemia drug Sprycel or dasatinib; and Genentech and Roche’s (ROG.VX) Herceptin or trastuzumab for breast cancer.

Last week, the FDA recommended genetic testing before AIDS patients take GlaxoSmithKline Plc’s (GSK.L) drug Ziagen.

In Europe, there are now 11 drugs — including Ziagen or abacavir for HIV and Novartis’ (NOVN.VX) leukemia drug Tasigna or nilotinib — that require the use of companion diagnostics.

Researchers at PricewaterhouseCoopers, a financial advisory and consulting firm, expect many more.

Diagnostics not only help ensure that patients who get drugs will benefit. Drug makers can use them to enrich clinical trials, cutting the costs of drug development, Tony Pillari, director of Healthcare Advisory Services at PricewaterhouseCoopers, said in a telephone interview.

“In drug development, time is money. If you can cut development times by even by a small percentage, it can result in huge cost savings,” Pillari said.

“Diagnostics now make possible enriched clinical trials. Rather than picking a random population, you can segment the population to focus on the people who are most likely to respond,” he said. (Editing by Maggie Fox and Peter Cooney)

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Francis Collins MD, PhD

GoogleNews.com, PharmExec.com, August 3, 2009  —  No one was surprised last month when the White House nominated world-famous geneticist Francis Collins for the top job at the National Institutes of Health (NIH). The driving force behind NIH’s Human Genome Project for 15 years, Collins is experienced in managing large research projects and big budgets and in making friends on Capitol Hill.

In the year since he left NIH, he actively supported President Barack Obama’s election campaign and wrote a book on personalized medicine that reflects his belief in the power of molecular biology to shape medicine and the world. Collins has expressed disappointment that important genomic discoveries have not led to new life-saving therapies, and he will want to use his new position to change that.

For pharma, Collins’ offers prospects of increased emphasis at NIH on translational research and more collaboration in developing drugs for orphan and neglected diseases. Comparative effectiveness research, he says, should identify subpopulation responses to treatment and support personalized medicine.

Collins has been highly praised for bringing in the human genome project ahead of schedule and below budget; as NIH director he will need all his administrative skills to manage the vast NIH complex and shape how its disparate institutes dole out more than $25 billion in grants to research organizations and scientists. NIH staffers see him as likely to favor big, high-profile projects over the needs of individual researchers. An evangelical Christian, he also will face pressure to clarify how his personal faith can co-exist with support for evolution and science.

Collins takes over NIH at an enviable time. The agency gained some $10 billion in extra funds through the economic recovery legislation enacted earlier this year, providing a nice addition to the agency’s $30 billion budget. Although Congress is not likely to provide such largesse in the future, some increases are likely.

Spurring Stem Cell Research
A high-profile task for Collins is to implement recently finalized guidelines on human embryonic stem cell research (hESC), which NIH issued just as Collins’ nomination was announced. The new program calls for an NIH panel of scientists, ethicists and advocates to assess that all candidate stem cell lines meet ethical standards for government-funded research:  that they are derived from leftover embryos created by in vitro fertilization, that donors understand their options and consent to research uses, and that there is no compensation to or pressure on donors to do so. NIH will establish a registry of all cell lines deemed eligible for federal funding, with an eye to reducing uncertainty and confusion in the research community.

The new rules were proposed last April after President Obama issued an executive order rescinding Bush administration restrictions on government-funded hESC studies. The new rule promises to vastly expand opportunities for research in this area, despite continued curbs on funding studies that use stem cells created solely for research purposes or cell lines derived through somatic cell nuclear transfer, a technique that many researchers consider highly promising. While life-saving medicines ultimately may emerge, a near-term benefit may be the development of new cellular assays for screening drug candidates and other methods useful in drug development.