ddn Online

The Blog of Drug Discovery News

Research efforts can help fragile young lives

Whether we are researchers or journalists, as we explore the landscape of the drug development world we are reminded just how fragile human life can be.

This week, I came across a story that a team of pediatric cancer researchers have identified variations in a gene as important contributors to neuroblastoma, the most common solid cancer of early childhood.

The study team, led by researchers at The Children’s Hospital of Philadelphia, found that common variants in the LMO1 gene increase the risk of developing an aggressive form of neuroblastoma, and also mark the gene for continuing to drive the cancer’s progression once it forms.

The team’s work appears online in Nature. According to their report, a cancer of the sympathetic nervous system that usually occurs as a solid tumor in the abdomen, neuroblastoma accounts for 10 percent of childhood cancer deaths.

According to its website, The Cancer Center at The Children’s Hospital of Philadelphia cares for more children with cancer than any other pediatric hospital in the United States. It is ranked second in children’s cancer care in the U.S. by U.S.News & World Report.

It is so sobering to think that the youngest and most vulnerable—our children—sometimes are engaged in a fight for their lives as they battle myriad issues that come with adult-sized problems.

The researchers found a significant association between neuroblastoma and the LMO1 gene, located on chromosome 11, detecting the strongest signal among patients with the most aggressive form of the disease. This portion of the study identified SNPs, changes in a single letter within the DNA sequence, which predispose a child to developing neuroblastoma.

The research team utilized genetic tools to decrease LMO1’s activity, and showed that this inhibited the growth of neuroblastoma cells in culture. Increasing LMO1 gene expression had the opposite effect, causing tumor cells to proliferate.

Because other genes in the LMO family are known to be active in acute leukemias, other researchers have been investigating potential anti-leukemia drugs to target portions of the LMO pathway.

This is just one example of all of the great work going on in labs in hospitals, academic institutions and other facilities in the United States and around the world.

The research offers great hope for children battling cancer. It also is further proof that the work being done in research labs around the world are yielding results that can take steps to eradicate the diseases that take a great toll on us emotionally and physically, regardless of sex, age or race.

Further, the study by researchers at The Children’s Hospital of Philadelphia shows how we can expand our knowledge base for translating genetic discovery to clinical issues through integrative genomics, combining SNP discovery arrays with gene expression arrays and other functional approaches.

With the great results coming from this work, perhaps the suffering of some of the small and meek can be eased.

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December 7, 2010 Posted by | Academia & Non-Profit, Announcements and Events, Labwork & Science, Uncategorized | Leave a comment

Gobble, gobble…but not too much, now

Those of you in Canada already celebrated your Thanksgiving Day in October. I’m not sure how many nations outside of North America even have such a celebration.

But I can probably rest assured that the residents of the United States will understand why there aren’t likely to be much in the way of updates this week, as our day of (American) football, turkey, stuffing, mashed potatoes, gravy, green bean casserole, pumpkin pie, family, friends and other things for which to give thanks is on Thursday (Thanksgiving Day). So, Wednesday of this week is scrambling to get my ddn work done and bake my Pumpkin Crunch dessert (a dish that has won me many a friend), Thursday will be a day to enjoy the holiday, and Friday will be the continuation of the long weekend that begins Thursday.

Sure, it’s entirely possible that some pharma news will crop up or an idea will burrow into my head and cause me to post something before Monday, but if not, see you next week, and here’s hoping not too many of us need to move up one or two belt notches over the coming several days.

November 23, 2010 Posted by | Uncategorized | | Leave a comment

For stem cell case plaintiff, faith and science go hand-in-hand

Yesterday, we shared a Q&A with the lead plaintiffs in the controversial federal lawsuit challenging federal funding for embryonic stem cell (eSC) research, Dr. James L. Sherley, a biological engineer at Boston Biomedical Research Institute, and Dr. Theresa Deisher, research and development director at AVM Biotechnology LLC in Seattle.

Both researchers agreed to field questions about their beliefs regarding eSC research. Deisher, who has been especially vocal about her Catholic faith and how it informs her research, also agreed to take a few questions about the connection she sees between her beliefs and science.

According to Deisher’s bio, she has 17 years of experience in scientific and corporate leadership positions involving research, discovery, production and commercialization of human therapeutics. She obtained her Ph.D. in molecular and cellular physiology from Stanford University. Prior to founding AVM Biotechnology in 2007, Deisher held positions at Repligen Corp. in Cambridge, Mass., ZymoGenetics Inc., Immunex and Amgen in Seattle and CellCyte Genetics Corp. in Bellevue, Wash. She has had 23 patents issued and has published numerous scientific manuscripts.

ddn: Do you find any conflict between your faith and the scientific research you engage in?

Deisher: I do not find any conflict between my faith, which is Catholic, and my research. My faith enhances my work. My Christian faith calls me to focus on drugs and treatments that are affordable so that the greatest number of people will benefit. My faith calls me to use reason and the order of natural law to determine, for instance, the stem cell most optimal for clinical use. My faith calls me to focus only on those treatments that will be effective. My faith also calls me to respect the intrinsic dignity of human life in my work.

ddn: How does your faith impact your research approach?

Deisher: My faith is completely complementary to my research, which focuses currently on stem cells for regenerative medicine and alternative vaccines.

Adult “self” stem cells, meaning a patient’s own stem cells, are affordable, compared to all other stem cell therapies. For the most part, therapies using adult stem cells will cost about $25,000 compared to Geron’s projected $500,000 for embryonic stem cell-based therapies. Adult “self” stem cells are found naturally in every organ, in each of us, and they are “preprogrammed’” to perform the functional regeneration that patients require. They also lack the issues of immune rejection or tumor formation that plague pluripotent stem cells such as embryonic stem cells. Adult “self” stem cells are far advanced in clinical trials, and in comparison to “patented” stem cell lines, they show more effectiveness in patients. Whether one believes in God or Darwin, one can arrive at an optimal stem cell for patients using objective measures, common sense and business criteria to generate the greatest good for the most people.

I would apply these same criteria to any type of treatment that I would work on, including biologics and small molecules: Will the therapy be affordable, or will only the very few benefit? Will the therapy be effective or merely enhance my stock price or financing temporarily? Will the therapy be undermined by adverse side effects? These criteria are sound business objectives and compatible with my faith.

November 11, 2010 Posted by | Academia & Non-Profit, Corporate, Government, Labwork & Science, Uncategorized | , , , , , , , , , , , , | Leave a comment

Q+A with the stem cell case plaintiffs

On the cover of our November issue (which you can download here), you can read about a controversial lawsuit that is at the center of one of our nation’s hottest current debates: embryonic stem cell (eSC) research. (See the story here.)

The lawsuit, Sherley, et al., v. Sebelius, et al., alleges that the order signed by President Barack Obama in March 2009 lifting a previous ban on federal funding for eSC research violates the Dickey-Wicker amendment, a 1995 law prohibiting the government from appropriating funds for research that involves the creation or destruction of human embryos for research purposes. The lawsuit also contends that President Obama’s order has intensified competition for government research funds—which are already in short supply—for researchers engaged in other kinds of stem cell research.

The case has been making its way through the courts for a while, but it made headlines in August when the U.S. District Court for the District of Columbia issued a preliminary injunction in the case, essentially bringing funding for embryo-destructive research to a screeching halt while the case is under consideration.

With the research community in uproar over the decision, less than a month later, the U.S. Court of Appeals temporarily suspended the injunction, arguing that it would cause irreparable harm to researchers, taxpayers and scientific progress while the case is appealed.

While Sherley v. Sebelius concerns the interpretation of law and competitive issues, the case has renewed the debate over the practice of stem cell research in the United States, a political and moral tug-of-war that has been waged for decades.

The debate centers on the creation of a human embryonic stem cell (eSC) line, which requires the destruction of a human embryo. Advocates of the pro-life movement are concerned with the rights and status of an embryo as an early-aged human life and equate eSC research with murder. Those opposing this view argue that these embryos are to be destroyed or stored for long periods of time past their viable storage life, and point out that stem cell research has the potential to dramatically alter approaches to understanding and treating diseases, and to alleviate suffering.

Science holds pros and cons for both sides of the moral debate. Adult stem cell research has achieved great levels of success and potential, but these stem cells are generally limited to differentiating into different cell types of their tissue of origin. Although some researchers are of the opinion that the differentiation potential of eSCs is broader than most adult stem cells, they may be rejected by the immune system—a problem that would not occur if a patient received his or her own stem cells.

Dr. James Sherley

As the case continues to play out in court, media attention is turning to the lead plaintiffs in the case, Dr. James L. Sherley, a biological engineer at Boston Biomedical Research Institute, and Dr. Theresa Deisher, research and development director at AVM Biotechnology LLC in Seattle. Although the pair admit they did not know each other prior to the case unfolding—they were reportedly “recruited” by attorneys seeking to challenge President Obama’s order—they both have certain beliefs about the ethics involved in eSC research, and strongly support a focus on adult stem cells.

Sherley, whose research focuses on the molecular and biochemical mechanisms of adult stem cells, has long been vocal about his opposition to human eSC research. He has described the position that eSCs hold the promise to cure or treat debilitating diseases “misinformation,” maintaining that adult stem cell research is “a viable and vibrant path to new medical therapies.” Sherley also once made headlines for protesting a decision by the Massachusetts Institute of Technology (MIT) to deny him tenure by going on a 12-day hunger strike. Sherley, who is African-American, has also publicly said he believes that MIT did not give him the freedom to challenge scientific orthodoxy the way the institution would have for a white colleague.

Dr. Theresa Deisher

Deisher, who works exclusively with adult stem cells, founded AVM Biotechnology “in response to growing concerns about the need for safe, effective, affordable and ethical medicines and therapeutic treatments,” with help from private donors. According to the company’s website, “The use of aborted fetal tissue and embryonic cells in the discovery, development and production of vaccines and pharmaceuticals … make it difficult for many physicians, pharmacists, scientists and healthcare professionals to navigate their fields of expertise without sacrificing their consciences.” You can see some of Deisher’s writing on the subject here.

As media scrutiny has intensified in the wake of the case, Sherley and Deisher have backed away from many interviews, but were gracious enough to take questions from ddn regarding their views about eSC research. Here are their responses:

ddn: What should the goal of stem cell research be?

Sherley: Like other NIH-funded research, the goal should be to increase our scientific knowledge about the natural world through the conduct of ethical scientific research towards the goal of improving human health.

Deisher: The goal should be to develop safe, effective and affordable therapies for human disease, adhering to the highest scientific ethical standards.

ddn: Are you against embryonic stem cell research as a practice, or the federal funding of it, or both? Why?

Sherley: Specifically, I wish to educate and alert the public that, first and foremost, human embryonic stem cell research is unethical according to pre-existing NIH guidelines for human subjects research; that its funding by NIH is illegal according to U.S. law as articulated by the Dickey-Wicker amendment; and that it continues to be misrepresented by many of its proponents who misstate its potential for providing medical advances and present it as if there were no alternatives, when if fact both adult stem cell research and traditional disease research are not only effective alternatives, but better ones in many respects.

Deisher: Human embryonic stem cell research does not meet the high ethical standards test. A human being is necessarily destroyed in the process of obtaining human embryonic stem cells, which is not an acceptable outcome according to U.S. human subjects guidelines. Additionally, the research is not necessary, another requirement of our human subjects guidelines, as superior alternatives are available using adult stem cells. According to human subjects research guidelines, even if parents give consent, research cannot be done if it is not necessary. Human subjects guidelines should be applied to all research, regardless of funding source, and should be applied to regulate research on human embryos.

ddn: What are viable alternatives to embryonic stem cells? How soon will they bring about therapies? What is their commercial potential?

Sherley: The viable alternatives are both adult stem cell research and traditional disease research. In particular, adult stem cell research addresses the development of new therapies based on repairing tissues or replacing tissues with regenerative cells. Such therapies based on adult stem cells are already a part of standard clinical practice. Bone marrow reconstitution with blood stem cells is one of the best known examples, but there is a large body of clinical research underway both to make blood stem cell treatments even more effective and to develop new therapies based on other types of adult stem cells. This clinical research includes commercial development of therapies for diseases like diabetes based on developing adult stem cells that renew the cells that make insulin. It is important that the public understands that proposed treatments based on human embryonic stem cells invariably require that they be converted into either adult cells or adult stem cells, which are ultimately required for any therapy that will repair, replace, or treat tissues in children and adults. When the public knows this, it then becomes imperative for it to ask proponents of human embryonic stem cell research, “What is your motivation?”

Deisher: Adult stem cell therapies are in late-stage clinical trials, having advanced extremely rapidly since their discovery in the late 1990s, entering clinical trials by 2002.  Prior to the late 1990s, scientific dogma held that adult stem cells did not exist outside of the blood system. These novel discoveries have brought promise to many patients suffering from grievous illness; unfortunately, the United States lags behind the rest of the first world in advancing these therapies because our academic scientists and elected officials have preferentially advanced human embryonic stem cell research, which is currently helping no one. Other alternatives include therapies that block tissue destructive pathways. For instance, Enbrel is a drug for rheumatoid arthritis that blocks the joint destroying action of a molecule called TNF. Once the destructive pathway is blocked, naturally present regenerative processes are able to replace the damaged joints.

ddn: Describe some of your current work in this area.

Sherley: My laboratory’s research is focused on developing methods for production of adult stem cells, discovering biomarkers that can be used to quantify adult stem cells, and elucidating cellular mechanisms that are important for adult stem cell function, health and longevity.

Deisher: My research focuses on the efficient delivery and retention of stem cells in diseased organs.

ddn: What should the government’s role be in stem cell research being done in the United States?

Sherley: Through its agent the NIH, its role should be the same as for other areas of research: Adhering to U.S. law, foster and fund ethical, high-quality research that has potential to positively impact human health.

Deisher: (References the NIH’s mission statement, which states, “NIH’s mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life and reduce the burdens of illness and disability. The goals of the agency are: To foster fundamental creative discoveries, innovative research strategies, and their applications as a basis for ultimately protecting and improving health; To develop, maintain and renew scientific human and physical resources that will ensure the nation’s capability to prevent disease; To expand the knowledge base in medical and associated sciences in order to enhance the nation’s economic well-being and ensure a continued high return on the public investment in research; and to exemplify and promote the highest level of scientific integrity, public accountability and social responsibility in the conduct of science.”)

Highlighted in red are NIH mandates that are not met by NIH funding of human embryonic stem cell research. The government’s role should be to actively promote research and clinical trials in areas that would not be adequately advanced by private industry. Adult stem cells from a patient’s own blood, bone marrow or other organs are not patentable, and therefore, absolutely require federal funding to bring these remarkable treatments to U.S. citizens. As taxpayer funds are used by the government for these purposes, one would hope that affordability would also be an important criterion for federal funding of clinical trials. Adult stem cell therapies are affordable, and will cost on average about $25,000, while embryonic stem cell therapies, if ever available, will be expensive and beyond the means of almost all U.S. taxpayers. Geron Corp. issued public statements in January 2009 estimating the cost of human embryonic stem cell-based therapies for spinal cord injury to be just under $500,000. Geron received significant NIH funding for this work.

ddn: How does the 2009 executive order from President Obama impact your access to research funds?

Sherley: Because the president’s order led to NIH instituting the illegal funding of human embryonic stem cell research, it injures all U.S. scientists working in other fields who compete for the same limited NIH resources. However, the greater injury is sustained by scientists whose research focuses on the recognized alternative to human embryonic stem cells, adult stem cells, because of the juxtaposition of all stem cell research applications in the NIH review process. At each phase of the NIH review process, bias and contempt, inspired by an illegal implementation of the president’s order, can occur against their research applications, even though they may be of the highest quality.

Deisher: The executive order initiated a process where preference in NIH requests for grant proposals and ultimate grant funding is now directed towards embryonic stem cell research. The 2009 executive order amplified congressional obsession with funding embryonic stem cell research, apparent since 2006. Every adult stem cell scientist and clinician is injured by the preferential emphasis and funding of embryonic stem cell research. Most egregiously, U.S. citizens are being denied adult stem cell therapies that are in development in Europe and other countries for heart attack, blindness, paralysis, stroke, diabetes, multiple sclerosis, lupus and other grievous human illness.

ddn: What can Americans do to get past the moral arguments in favor of or against embryonic stem cell research, in order to make sure that we are still working toward finding cures for devastating diseases and conditions?

Sherley: Americans would have no dilemma to ponder, if they were better informed that human embryonic stem cells have very little potential to lead to cures for devastating diseases and conditions. The No. 1 sales pitch pushed for these cells, the “ability to make any cell in the body,” is their fatal flaw for providing new medical therapies. For effective tissue and organ therapies, regenerative cells are needed that can continuously replace the mature cells found in just the sick or ailing tissue or organ. Human embryonic stem cells cannot do this. Adult stem cells can. Since human embryonic stem cells make other cells that are not needed, if they were used, they would give the patient another well-known, very difficult-to-treat disease.

Deisher: Science should never be above moral scrutiny and one only needs a brief history lesson to know this. On another note, I hear arguments regularly that we should not deter human embryonic stem cell research because of the moral objections of a minority. This is absurd, as our entire scientific research ethical oversight is predicated on respect for the moral objections of a minority in our country. Respect for animal rights and concern for ethical research conduct using animals in experiments regularly deters experiments that are scientifically and economically expedient. Respect for ethical concerns as they relate to human subjects research should receive no less deference. However, Americans do not need moral arguments to oppose embryonic stem cell research; embryonic stem cells are known to form tumors, they would require lifelong immune suppression that itself can cause hypertension, osteoporosis and other nasty side-effects, and human embryonic stem cell products would be too expensive for Americans to afford.

Deisher was also kind enough to field questions about how her Catholic faith informs her approach to stem cell research. We’ll bring you that Q&A very soon.

November 10, 2010 Posted by | Academia & Non-Profit, Government, Labwork & Science, Uncategorized | , , , , , , , , , , , , , | Leave a comment

Sequencing, drugs and rock ‘n’ roll: A look at Ozzy’s genome

All aboard

Scientists have stepped up to take a ride on the rails of the crazy train, sequencing and analyzing the full genome of heavy metal rocker Ozzy Osbourne.

And if you thought all rock stars were Neanderthals who bark at the moon, at least in the case of Ozzy Osbourne, you’d be partially right.

Known as the Prince of Darkness and the beheader of bats and birds, the deeper question might be just what the genetic code will reveal about the former Black Sabbath frontman.

In a recent column in the Sunday Times of London, Osbourne admitted his skepticism for the project. “The only Gene I know anything about is the one in Kiss,” he wrote.

Then, he wondered if, just maybe, he might have something to offer science.  He stopped being paranoid and stepped up to the plate for science.

“I was curious,” he wrote in his column. “Given the swimming pools of booze I’ve guzzled over the years—not to mention all of the cocaine, morphine, sleeping pills, cough syrup, LSD, Rohypnol…you name it—there’s really no plausible medical reason why I should still be alive. Maybe my DNA could say why.”

As it turns out, Osbourne has said that if genetic testing determines he has a risk of developing an untreatable disease such as Alzheimer’s, he’d rather not know about it.

In July, the Prince of Darkness let a little blood for Cofactor Genomics, a St. Louis–based company, to sequence. Knome Inc., which also helped raise money for the project, analyzed the data.

With that, Ozzy joined the likes of DNA co-discoverer James Watson and Harvard University professor Henry Louis Gates on the short roster of people to have their full genome sequenced and analyzed.

Osbourne and his wife, Sharon, talked about the heavy metal singer’s genome sequencing test at the TEDMED conference in San Diego.

The couple joined several genetics experts at the four-day TEDMED conference, which ended Oct. 29 at the Hotel del Coronado. About 600 people paid $4,000 each to attend the series of short talks delivered by leading scientists, authors, executives and celebrities.

Osbourne has spent decades living the rock and roll lifestyle. Because of his fast-living past, he wondered just why anyone would want to do such research one someone who spent decades abusing alcohol and drugs and took self-destructive behavior to an art form.

He also didn’t understand the potential for the testing. .

“I must confess that I don’t really understand this,” Osbourne told the TEDMED audience. “I find it interesting, but I don’t really understand what it means.”

Sharon Osbourne convinced him to take the test, though she admitted that her motives were selfish.

“I’ve always said that at the end of the world, there would be roaches, Ozzy and Keith Richards,” she said. “It’s fascinating to me how his body can endure so much, and he’s still going. I was just really fascinated by his body chemistry.”

According to the analysis, Osbourne has about 300,000 novel variants, a figure similar to that of other newly sequenced genomes. (The number of novel variants discovered per genome will fall as more people are sequenced.)

I guess nobody should be surprised that among the things revealed by the test is that Osbourne has a higher than average chance of being an alcoholic.

Additionally, he doesn’t metabolize caffeine very well, has a gene tied to smelling limitations and is a distant relative of comedian Stephen Colbert, some of the people who died nearly 1,000 years ago at Pompeii, Italy, during the eruption of Mount Vesuvius, and prehistoric Neanderthals.

Osbourne also carries a variant in the ADH4 gene that may well explain “his ability to ingest enormous quantities of alcohol” without killing himself, Jorge Conde, co-founder of Knome Inc., told the Toronto Star.

“If there’s a gene for addictive behavior, you’d have thought mine would be written in pink neon,” Osbourne reflected in his column in the Sunday Times.

He also has a variation of a gene known as AVPR1A that was linked to musical abilities in 2009 by researchers who studied the genetic makeup of 19 families in Finland.

“We certainly want to sample a larger sample of musicians to explore that,” said Nathaniel Pearson, a geneticist with Knome.

Most unusually, the analysis found that Osbourne carries two versions of the COMT gene: both the warrior and the worrier variant.

“Those two sides of my personality sum me up perfectly,” Osbourne told the TEDMED crowd.

He doesn’t have any of the markers tied to Alzheimer’s risk, and his wife checked those results before they were given to him.

The blood sample taken from Ozzy Osbourne in July was sequenced in a machine made by Life Technologies of Carlsbad, Calif.

At TEDMED, Life Technologies Chief Executive Greg Lucier showed off the company’s new Personal Genome Machine, which uses tiny chemical pH meters to identify DNA base pairs.

Other sequencers use chemical color tags, lasers, high-tech cameras and super computers in a process that takes more time and costs more money.

Lucier said medical science is on the cusp of a genomics revolution.

“We’re finding new gene associations (with diseases) each and every day,” he told the San Diego Union-Tribune. “There is incredible momentum happening (among physicians) to learn genomics and apply it to care.”

November 2, 2010 Posted by | Academia & Non-Profit, Corporate, Labwork & Science, Uncategorized | , , , , | Leave a comment

Eye of the beholder

There are good drugs, there are bad drugs and there are questionable drugs.

But except in cases where a drug is clearly harming people (like, say, making them drop dead of heart attacks in droves), the value of a drug is a matter of perspective. Some argue that we overmedicate people, particularly in the Western nations, and others say we need to have more pills for everything. One person’s passion for developing a drug for an orphan disease is another person’s idea of a waste of money.

In any case, on this fall Friday, let the following image remind you that sometimes, it’s all a matter of perspective:

Have a good weekend, everyone.

October 1, 2010 Posted by | Uncategorized | , , , | Leave a comment