July 23, 2012

redOrbit Staff & Wire Reports Your Universe Online

Researchers from several prominent medical institutions claim that they have identified several genetic mutations responsible for medulloblastoma, the most common malignant type of childhood brain tumor.

There are four recognized subtypes of medulloblastomas, which occur in the part of the brain responsible for controlling balance and other complex motor functions (the cerebellum), Boston Childrens Hospital researchers explained in a recent statement.

These tumors are treated through a combination of surgery, chemotherapy, and radiation, and while survival rate for this form of cancer is approximately 70%, hospital officials note that those who overcome the disease are usually not able to live independently due to side-effects related both to the tumor and the treatment methods.

Doctors have historically classified medulloblastoma patients as either standard or high risk based on biopsy results, but have long suspected that what we call medulloblastoma could actually be several different diseases, they said. Over the last two years, studies by researchers have bolstered this view by dividing medulloblastoma into four molecular subtypes based on gene expression profiles and copy number variations. Each subtype has a distinct survival rate, ranging from 20 to 90 percent.

Now, Dr. Scott Pomeroy, Neurologist-in-Chief at Boston Childrens Hospital and a neuro-oncologist at the Dana-Farber/Childrens Hospital Cancer Center (DF/CHCC), and colleagues used advanced sequencing techniques to study the medulloblastoma tumors of 92 patients. They then compared that information with DNA obtained from matched blood samples from those same subjects and discovered 12 single-letter errors in the genetic code (also known as point mutations) that occurred frequently in all types of the cancer.

Functionally, the mutated genes fell into two broad categories: genes like Shh and Wnt that play direct roles in molecular pathways controlling cell growth, and genes like DDX3X and GPS2 that play more of a coaching role, modulating the activity of other genes, the researchers said. Taken as a whole, the studys results confirm the view of medulloblastoma as a family of tumors driven by disruptions in just a few common mechanisms. However, the form those disruptions take the actual mutations or genomic changes can vary from tumor to tumor.

We tend to treat all medulloblastomas as one disease without taking into account how heterogeneous the tumors are at the molecular level, Yoon-Jae Cho, an assistant professor of neurology and neurological sciences at the Stanford University School of Medicine and senior author of a report published by the journal Nature, said in a statement. This paper represents a finer-grained view of the genetic landscape of these tumors and provides us with some leads on how to develop new therapies.

While no single tumor in the study carried all 12 mutations, the researchers said that they were able to categorize the tumors according to which mutations they possessed, discovering that certain tumors can be resistant to standard treatments because of their genetic signatures. Cho said that treatment of the disease could be enhanced, and post-treatment side effects reduced, if doctors characterized the genetic signatures of medulloblastoma patients first.

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Genetic Mutations Responsible For Childhood Brain Tumors

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News | Health

China was the first country to approve a gene therapy product for commercial use, in 2004. The U.S. has yet to endorse any such treatments and the field has been plagued by carcinogenicity

By Daniel Cressey and Nature magazine | July 23, 2012

Image: Flickr/hermida

From Nature magazine

Europes drugs regulator has for the first time recommended a gene therapy medicine for approval.

Glybera, a treatment for patients who cannot produce enough of an enzyme crucial for breaking down fat, was backed by the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP). This recommendation has to be endorsed by the European Commission before it becomes available, but it would be unusual for the Commission to reject the recommendation.

Gene therapy involves transferring genes into patients to treat their diseases. In this case Glybera uses a virus injected into a patient to deliver a working copy of a gene for producing lipoprotein lipase (LPL). LPL deficiency affect no more than one or two people in a million.

Back in 2004 China became the first country to approve a gene therapy product for commercial use, with a treatment for cancer. But Europe and the United States have yet to endorse any gene therapy treatments and the field has been plagued by issues such as carcinogenicity.

Jrn Aldag, chief executive of uniQure, the Amsterdam-based company that owns Glybera, says todays announcement from the EMA is an overdue signal to the gene therapy community that things are changing. It unlocks the potential, he told Nature. You will see more investment coming.

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Europe Nears First Approval for Gene Therapy Treatment

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The European Medicines Agency has recommended the use of gene therapy for a rare genetic disease which leaves people unable to properly digest fats, BBC News reported. Before doctors can start treating the disease with gene therapy they must wait for it to be approved byThe European Commission.

According to the BBC, lipoprotein lipase deficiency affects one in a million people. People suffering from lipoprotein lipase deficiencyhave damaged copies of a gene which is essential for breaking down fat. It leads to fat building up in the blood, abdominal pain and life-threatening pancreatitis (inflammation of the pancreas). So much fat can accumulate that the blood looks white rather than red.

Dr. Daniel Gaudet, a professor of medicine at the University of Montreal, told The New York Times,Its the equivalent of having a 10 percent cream in your bloodstream."

With gene therapy, patients are provided with correct copies of defective genes that cause genetic disorders, according to the New York Times.

UniQure, a Dutch company, developed a new gene therapy called Glybera. According to the LA Times, the treatment is injected into the patient's legs in a series of shots at one sitting. Gaudet tested the gene therapy on 27 people in clinical trials. The trails showed that the injections are long-lasting and provide at least partial control of lipoprotein lipase deficiency with no apparent adverse effects.

The European Commission has rejected Glybera three times before due to insufficient evidence of its effectiveness.

More from GlobalPost:Scientists may have found the key to a longer life

http://www.globalpost.com/dispatch/news/health/120723/gene-therapy-lipoprotein-lipase-deficiency-close-approval-europe

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Gene therapy for lipoprotein lipase deficiency close to approval in Europe

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DEL MAR, Calif., July 23, 2012 /PRNewswire/ -- iDiverse announced that it has discovered a yeast gene that when inserted into yeast and properly modulated can increase ethanol production yield by up to 34%.

"The gene functions by protecting the yeast against some of the lethal stresses encountered in the bioproduction process," said John Serbin, Chief Business Officer at iDiverse. "In its current embodiment, it allows yeast to produce significantly more ethanol under the severe conditions of high concentrations of acetic acid and low pH. These critical conditions occur when fuel ethanol is produced from corn or sugarcane and are yet more severe in the newest generation of fermentation processes using lignocellulosic biomass as feedstock. Our constructs have been tested in several commercial yeasts. We believe that they can improve the performance of any yeast facing lethal bioproduction environments."

"The economic impact of this can be huge," said John Burr, president and CEO of iDiverse. "If our technology is effective at large-scale, it could increase the efficiency of installed fuel ethanol plants, enhance yields from corn and sugarcane feed stocks, and help manufacturers bridge the fuel ethanol production gap until the next generation biomass plants come on-line. In addition, we think we can help increase the manufacturing output of cellulosic biomass technologies under development.

"Also, our technology is ready to be used in applications beyond fuel ethanol. Those include the bioproduction of industrial enzymes, research reagents, and pharmaceuticals. Our technology will provide benefits to biomanufacturing cell types beyond yeast, such as CHO, insect, fungal, and algal cells."

About iDiverse iDiverse, Inc. is a privately-held biotechnology company dedicated to developing genetically enhanced cell lines for use in the bioproduction of fuel ethanol, industrial enzymes, and pharmaceuticals. It also provides genetic technology for creating plants that are resistant to a wide range of biological and environmental stresses.

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iDiverse Discovers Yeast Gene that Increases Fuel Ethanol Production Yield

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A little over two years ago I put up some posts on Jewish genetics due to the publication of some really exciting research. Looking at the referrals I noticed two trends which together were relatively bizarre. People would look at the same PCA plot and conclude that:

First, some context. Most of these referrals were from websites with white nationalist or quasi-white nationalist sympathies. The non-Jews of this set tended toward the position that Jews were non-white, while the Jews felt that the genetic results vindicated the whiteness of Jews. In some cases the links were from Jews who were not necessarily white nationalists, but were also keen on making it clear that European Jews were not schwartza.

To me the whole issue was bizarre, and it entailed that I monitor the comments of those posts pretty strictly. But I believe that a much milder version of the question crops up whenever people ask if European Jews are more European or Middle Eastern. The main conundrum in the whole framing of the question is that both European and Middle Eastern are highly heterogeneous constructions, and there isnt a very good demarcation of which populations are which on the liminal margin. In contrast, the difference between East Asians or Sub-Saharan Africans and West Eurasians is more clear and distinct. In-between populations such as Uyghurs and Ethiopians seem to be relatively recent admixtures, suggesting that these three geographical races have had very low gene flow for long periods of time. Not so between Europeans and Middle Easterners.

Because of this issue it is very easy to prove that Jews are or are not white through a facile selection biasing of the results. When you have groups which overlap, or are ill-defined, does it surprise that the science itself produces results which are somewhat ill-defined and easily subject to disputation?

Here are two results from The genome-wide structure of the Jewish people. First, lets look a PCA, where the first (vertical) component explains the largest proportion of the variance, and the second component (horizontal) the second largest component of the variance:

Now lets look at a table which shows allele sharing distance between two pairs of populations. Ive taken the results from the supplements, and limited the population set. Additionally, Ive taken the value, and standardized it so that the smallest distance (Iraqi Jew to Iraqi Jew) is set to 0, and larger values indicate greater difference in allele values across two populations.*

Are there clear conclusions you can derive from this? If you have an ideological ax to grind you almost certainly can. Overall a major issue here is that were often looking at summaries, when some of these populations have undergone recent admixture. The Turks, Yemenis, Russians, and Palestinians, all have non-West Eurasian admixture (East Eurasian in the case of Turks and Russians, African in the case of Yemenis and Palestinians). This is going to elevate their distance from Ashkenazi Jews. I suspect that the Russian value would be the same as the Lithuanian if you only compared West Eurasian ancestry to West Eurasian ancestry. But this is recent admixture. I suspect ancient admixture matters too. In relation to Sardinians and North Italians the Tuscan populations seems particularly enriched in a West Asian element. Though I do not discount the ASD value being so low between Ashkehani Jews and Tuscans being a function of ancient Italian admixture with Western Jews, I think it may be that this West Asian admixture brings this group closer to Jews, and so may predate real admixture between Jews and non-Jews (because Jews did not exist when this West Asian element became prominent in Italy!).

I could say a lot more. This is complicated and not cut & dried. But I think the different statistics are not showing us whether Jews are white or not, because thats not fundamentally a question which relies purely on genetics. Being white is not totally uncoupled from genetics. Someone of Chinese of African appearance could never be white. Genetics is a necessary condition, but it is not a sufficient condition of whiteness. So, for example, Middle Eastern non-Muslim populations regularly assimilate to whiteness, while Muslims do not. To my knowledge no one thought of Jacques Derrida as a non-white intellectual, despite his Algerian Sephardic Jewish background. But if Jacques Derrida had converted to Islam, and passed himself off as an Algerian Arab or Berber, he would have become non-white.

Link:
Are Jews white? | Gene Expression

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ScienceDaily (July 22, 2012) Researchers at the Stanford University School of Medicine and Lucile Packard Children's Hospital have identified several gene mutations responsible for the most common childhood brain tumor, called medulloblastoma, adding evidence to the theory that the diagnosis is a group of genetically distinct cancers with different prognoses. These and accompanying findings are likely to lead to less-toxic, better-targeted treatment approaches over the next two years, the researchers said.

"We tend to treat all medulloblastomas as one disease without taking into account how heterogeneous the tumors are at the molecular level," said Yoon-Jae Cho, MD, an assistant professor of neurology and neurological sciences at Stanford, a pediatric neurologist at Packard Children's and the senior author of the new research. "This paper represents a finer-grained view of the genetic landscape of these tumors and provides us with some leads on how to develop new therapies."

The research, which appeared online in Nature July 22, is part of a large, ongoing effort to characterize genetic errors in medulloblastoma. Two companion studies on which Cho is a co-author will be published simultaneously with his paper. The three papers came from a consortium that involves scientists at Stanford, Packard Children's, the Broad Institute, Children's Hospital Boston, the Dana-Farber Cancer Institute, the German Cancer Research Center, Brandeis University and the Hospital for Sick Children in Toronto.

Current treatment for medulloblastoma, which originates in the cerebellum and affects about 250 U.S. children each year, begins with surgery to remove as much of the tumor as possible. Patients then receive a combination of radiation and chemotherapy, but the treatments are not tailored to the tumor's genetic characteristics.

Cho's team extracted DNA from 92 medulloblastoma tumors and compared it with DNA from matched blood samples from the same patients, uncovering 12 significant "point mutations" -- single-letter errors in the genetic code -- that occurred frequently in the brain cancer. A handful of the mutations had been previously identified in smaller studies of medulloblastoma, but several mutations were novel in both medulloblastoma and in cancer.

Among the newly identified mutations was one in an RNA helicase gene, DDX3X, which Cho said is the second-most common mutation in medulloblastoma tumors. "Mutations in this gene have now also been identified in other tumor types, such as chronic lymphocytic leukemia, and head and neck tumors," he said.

However, the researchers found that it was rare for the same gene mutated in several different patients' tumors. More commonly, mutations involving a set of genes regulating a single biological pathway were found in the tumors -- a pattern that is emerging across cancer genome sequencing efforts.

Though no single tumor in the study carried all 12 mutations, the researchers were able to categorize the tumors according to which mutations they possessed. "We now understand that there are certain tumors with particular genetic signatures that are really resistant to standard treatments," Cho said. Children with medulloblastoma do not routinely have their tumors' genetic signatures characterized, but Cho believes that such characterization coupled with targeted therapies could greatly enhance tumor treatment.

About two-thirds of medulloblastoma patients now survive five years past diagnosis, but many survivors suffer lasting physical or intellectual side effects from their cancer treatments. Drugs tailored to a tumor's genetic profile have the potential to save more patients while reducing side effects, Cho said.

Several of the mutations discovered affect cellular signals that switch large groups of genes on and off. "The dysregulation of these 'epigenetic programs' is becoming a common theme not only in medulloblastoma but across cancer," Cho said. Such pathways may be good targets for cancer drugs; indeed, drugs targeting one such pathway (histone methyltransferases) are currently in pre-clinical development, while agents against another pathway (Hedgehog signaling pathway) are entering phase-2 clinical trials for medulloblastoma.

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Genetic mutations that cause common childhood brain tumors identified

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Disna Mudalige

Cutting edge medical technology known as gene therapy has been developed by Indian doctor Sunita Rana Agarwal along with her husband Punkaj Sondhi with positive results, to control all kinds of, eye related illnesses, arthritis, diabetes, cancer, trauma, congenital errors and HIV AIDS.

Gene therapy works as an anti- aging, regenerative and rejuvenating treatment which leads to a healthier life.

Dr Agrawal on a brief visit to Sri Lanka told the Daily News the technology was developed following extensive research for around 20 years and it had been tested on about 12,000 patients during the past eight years.

A drop of blood is taken from the patient through a needle and customised with the DNA activator, which is the proprietary formula, that in turn makes a young and healthy DNA which is customised to that particular patient.

It is a course of 10 injections through 10 days which is much affordable compared to conventional therapies, Dr Agarwal said explaining how the gene therapy is applied.

She said this is a simple technology for which the patient does not have to be hospitalised and that it does not have any side effects. Dr Agarwal said gene therapy is a molecular based therapy.

She said they are at present dealing with pharmaceutical companies to take this product, which would basically work as a panacea, to the next level.

Dr Agarwal provided her voluntary service in the North and East during the late 1980s as an eye surgeon. She said the people in that region at that time had not seen an eye doctor for decades since nobody was willing to work under those risky conditions.

Dr Agarwal also commended the tremendous change in Sri Lanka at present compared to her previous visit, adding there is a remarkable improvement in every sphere.

Excerpt from:
Gene therapy for range of illnesses

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By Mark Long

The first gene-therapy drug in the Western world likely moved a step closer to the market Friday, as European regulators recommended approval of a medicine to treat a rare disease that causes fat to build up in the blood.

Dow Jones Newswires reports that a European Medicines Agency committee backed approval of Glybera, which was developed by Dutch biotech firm uniQure to treat patients with lipoprotein lipase deficiency, or LPLD.

The European Commission usually backs such recommendations from the drug regulator, which had rejected Glybera three times before.

In gene therapy, scientists try to correct a problem caused by a defective or non-functioning gene by replacing it with a functioning gene. Research efforts had faded for years amid concerns it was too risky and complex to be safe and effective. But findings from several studies rekindled interest in the approach, as WSJ reported in 2010.

No gene therapy drugs are on the market in the West, though one to treat cancer was approved in China in 2003, the Associated Press notes in its story on the thumbs up for Glybera. The AP says the agency recommended approval only with tough restrictions and uniQure will have to set up a registry to track patients.

Patients with LPLD cant handle fat particles in their blood plasma. This leads to recurring, severe abdominal pain and pancreatitis. The disease affects one or two out of every million people.

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West’s First Gene Therapy Gets European Backing

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An ongoing legal battle over gene patents has led many scientists to ask whether such claims help or hinder research. That question will be debated once more on 20 July when Myriad Genetics, a diagnostic company in Salt Lake City, Utah, returns to the US courts to argue that its patents on theBRCA1 and BRCA2 gene variants linked to inherited breast and ovarian cancer are valid. Currently, the patents give Myriad exclusive rights to conduct diagnostic tests on the genes. The judges are expected to issue an opinion by late summer. The case is important because thousands of genes have been patented in the United States, and no one is sure what will happen if the judges rule Myriad's patents invalid. Natureexamines what the Myriad case means to biotechnology and genetic medicine.

An argument over whether isolated DNA is patentable is at the centre of a US court case on existing gene patents.

Alfred Pasieka/Getty Images

In the United States, 'laws of nature' are not able to be patented, along with abstract ideas. The argument against Myriad's patents centres on whether isolated DNA is the same as native DNA, which is defined as a law of nature. If the court decides that the patents are invalid, that ruling would reverse more than 20 years of precedent, during which companies and academic researchers have patented thousands of genes. Some of these genes form the basis of diagnostic tests that determine when someone might respond well to a given therapy, or whether theyre at risk of a disease or a drug side effect, for example.

Although the courtsupheld Myriads patents in July 2011, the Supreme Court ordered the Appellate Court to reconsider the case in light of a ruling in March 2012 against the diagnostics company Prometheus Laboratories in San Diego, California (see 'US Supreme Court upends diagnostics patents'). Prometheus held patents on a method of determining drug dosage for a patient on the basis of the amount of certain components in their blood. According to the judge, this test merely reiterated a law of nature the relationship between the concentration of blood components and the likelihood that a drug dosage will be harmful or ineffective. Legal briefs recently filed by the US Department of Justice urge the judges to consider whether Myriad's patents 'tie up' the future use of laws of nature, as decided in the case against Prometheus.

Yes, according to the American Civil Liberties Union (ACLU) in New York, a legal group that represents the plaintiffs in the case, who include researchers, scientific societies and women with cancer. By claiming a law of nature, they can stop every other lab from performing tests, even with different testing methods, says ACLU attorney Sandra Park. Although there are some 8,000 publications on BRCA genes, which testify to the fact that research on the genes is ongoing, Myriad prevented at least five researchers who are some of the plaintiffs in this case from testing women in-house as part of their academic studies. Its within [Myriads] power to give licences to scientists, Park says, but the way theyve exercised their rights shows that they are intent on maintaining a monopoly. Legal briefs filed by DNA co-discoverer James Watson urge the judges to consider whether the patent leaves the public free to study the genes encoding BRCA1 and BRCA2.

Venture capitalists would be reluctant to invest in a small biotechnology firm if there was no secure patent protection, says Hans Sauer, an intellectual-property lawyer at the Biotechnology Industry Organization in Washington DC, a trade association for biotech companies that has filed a brief in favour of Myriad. Its already quite hard to get good patent protection in the area of personalized medicine, and theMyriadcase adds another layer of complexity, he notes. Companies will still be able to patent genes if Myriad loses its case, but the patents might need to be more narrowly defined and so might not protect companies as effectively, he predicts. For example, a patent might protect a kit that detects specific mutations within a gene associated with causing colon cancer, the result of which helps physicians to tailor their patients treatment. The issue with narrower patents, however, is that other companies can design tests that detect different mutations, or they could develop kits that detect the same mutations using different reagents.

Scientists tend to ignore patent claims on genes or genetic diagnostic methods because the patent-holding companies generally reserve litigation for individuals who seek to profit from their product, Sauer says. Researchers have occaisonally been issued cease and desist letters to stop them working on patented genes but these cases rarely, if ever, result in lawsuits. One way to increase researchers security might be to explicitly allow experimental use exceptions, as occurs in European patent law. It works well in other countries, says Sauer, so I dont see why it wouldnt work here.

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The great gene-patent debate

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Public release date: 20-Jul-2012 [ | E-mail | Share ]

Contact: Jenny Eriksen Leary jenny.eriksen@bmc.org 617-638-6841 Boston University Medical Center

(Boston) A research study led by Boston University School of Medicine (BUSM) and the University of Exeter in the United Kingdom, in collaboration with a global consortium, has identified genetic markers that influence a protein involved in regulating estrogen and testosterone levels in the bloodstream. The results, published online in PLoS Genetics, also reveal that some of the genetic markers for this protein are near genes related to liver function, metabolism and type 2 diabetes, demonstrating an important genetic connection between the metabolic and reproductive systems in men and women.

Andrea D. Coviello, MD, assistant professor of medicine at BUSM and an endocrinologist at Boston Medical Center, is one of the paper's lead authors. This study was done in collaboration with the Framingham Heart Study and investigators from 15 international epidemiologic studies participating in the Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) consortium.

Sex hormone-binding globulin (SHBG) is the key protein that carries testosterone and estrogen in the bloodstream in both men and women. As the main carrier of these sex hormones, SHBG helps to regulate their effects in different tissues and organs in the body. In addition to effects on reproduction in men and women through regulation of sex hormones, SHBG has been linked to many chronic diseases including type 2 diabetes and hormone-sensitive cancers such as breast and prostate.

Previous family studies have demonstrated that approximately 50 percent of the variation in SHBG concentrations in the bloodstream is inherited from parents, suggesting that SHBG levels are under significant genetic control. However, little has been known about the specific genes that influence SHBG levels.

Investigators examined human genomes from 21,791 men and women to determine which genes influence SHBG levels and validated the results from this genome-wide association study (GWAS) in an additional 7,046 men and women. They identified 12 single-nucleotide polymorphisms (SNPs), or DNA sequence variations, associated with the concentration of SHBG circulating in the bloodstream. However, these SNPs combined explain only 16 percent of the variation of SHBG in men and eight percent in women, respectively, indicating that SHBG levels are affected by many other factors as well.

The results also showed that the SNPs that influence SHBG levels are near genes related to liver function, fat and carbohydrate metabolism and type 2 diabetes. In addition, there were genes that had stronger effects in one sex compared to the other.

"These findings underscore the connection between the reproductive system and metabolism in both men and women, and may help explain sex differences observed in some metabolic diseases, particularly type 2 diabetes," said Coviello.

###

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BUSM researchers identify genetic markers for testosterone, estrogen level regulation

Recommendation and review posted by Bethany Smith

ScienceDaily (July 20, 2012) A research study led by Boston University School of Medicine (BUSM) and the University of Exeter in the United Kingdom, in collaboration with a global consortium, has identified genetic markers that influence a protein involved in regulating estrogen and testosterone levels in the bloodstream. The results, published online in PLoS Genetics, also reveal that some of the genetic markers for this protein are near genes related to liver function, metabolism and type 2 diabetes, demonstrating an important genetic connection between the metabolic and reproductive systems in men and women.

Andrea D. Coviello, MD, assistant professor of medicine at BUSM and an endocrinologist at Boston Medical Center, is one of the paper's lead authors. This study was done in collaboration with the Framingham Heart Study and investigators from 15 international epidemiologic studies participating in the Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) consortium.

Sex hormone-binding globulin (SHBG) is the key protein that carries testosterone and estrogen in the bloodstream in both men and women. As the main carrier of these sex hormones, SHBG helps to regulate their effects in different tissues and organs in the body. In addition to effects on reproduction in men and women through regulation of sex hormones, SHBG has been linked to many chronic diseases including type 2 diabetes and hormone-sensitive cancers such as breast and prostate.

Previous family studies have demonstrated that approximately 50 percent of the variation in SHBG concentrations in the bloodstream is inherited from parents, suggesting that SHBG levels are under significant genetic control. However, little has been known about the specific genes that influence SHBG levels.

Investigators examined human genomes from 21,791 men and women to determine which genes influence SHBG levels and validated the results from this genome-wide association study (GWAS) in an additional 7,046 men and women. They identified 12 single-nucleotide polymorphisms (SNPs), or DNA sequence variations, associated with the concentration of SHBG circulating in the bloodstream. However, these SNPs combined explain only 16 percent of the variation of SHBG in men and eight percent in women, respectively, indicating that SHBG levels are affected by many other factors as well.

The results also showed that the SNPs that influence SHBG levels are near genes related to liver function, fat and carbohydrate metabolism and type 2 diabetes. In addition, there were genes that had stronger effects in one sex compared to the other.

"These findings underscore the connection between the reproductive system and metabolism in both men and women, and may help explain sex differences observed in some metabolic diseases, particularly type 2 diabetes," said Coviello.

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Genetic markers for testosterone, estrogen level regulation identified

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Public release date: 20-Jul-2012 [ | E-mail | Share ]

Contact: Andrew Gould andrew.gould@pcmd.ac.uk 44-188-438-346 The Peninsula College of Medicine and Dentistry

A research study led by the Peninsula College of Medicine and Dentistry, University of Exeter, and Boston University School of Medicine, in collaboration with a global consortium, has identified genetic markers that influence a protein involved in regulating oestrogen and testosterone levels in the bloodstream.

The results, published online in PLoS Genetics, also reveal that some of the genetic markers for this protein are near genes related to liver function, metabolism and type 2 diabetes, demonstrating an important genetic connection between the metabolic and reproductive systems in men and women.

The study was carried out in collaboration with the Framingham Heart Study and investigators from 15 international epidemiologic studies participating in the Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) consortium.

Sex hormone binding globulin (SHBG) is the key protein that carries testosterone and oestrogen in the bloodstream in both men and women. As the main carrier of these sex hormones, SHBG helps to regulate their effects in different tissues and organs in the body. In addition to effects on reproduction in men and women through regulation of sex hormones, SHBG has been linked to many chronic diseases including type 2 diabetes and hormone-sensitive cancers such as breast and prostate.

Previous family studies have demonstrated that approximately 50 per cent of the variation in SHBG concentrations in the bloodstream is inherited from parents, suggesting that SHBG levels are under significant genetic control. However, little has been known about the specific genes that influence SHBG levels.

Investigators examined human genomes from 21,791 men and women to determine which genes influence SHBG levels and validated the results from this genome-wide association study (GWAS) in an additional 7,046 men and women. They identified 12 single-nucleotide polymorphisms (SNPs), or DNA sequence variations, associated with the concentration of SHBG circulating in the bloodstream. Although these genetic variants only explain a small fraction of the sex hormone variability seen between individuals, they could provide insight into the diseases connected to sex hormone regulation.

The results showed that the SNPs that influence SHBG levels are near genes related to liver function, fat and carbohydrate metabolism and type 2 diabetes. In addition, there were genes that had stronger effects in one sex compared to the other.

"These findings highlight the diverse range of biological processes that may be impacted by sex hormone regulation," said Dr. John Perry of the Peninsula College of Medicine and Dentistry, University of Exeter.

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Genetic markers for testosterone and estrogen level regulation identified

Recommendation and review posted by Bethany Smith

Salt Lake City-based Myriad Genetics expressed confidence Friday it would prevail in defending its patents of genes related to breast and ovarian cancer in a case being closely watched nationally by researchers and the biotech industry.

Myriad attorneys appeared for the second time before a three-judge panel of a federal appeals court in Washington, D.C., to defend patents related to the two genes after the U.S. Supreme Court sent the case back for reconsideration of an earlier decision that upheld most of Myriads patents. That came after the Supreme Court struck down patents in a case revolving around some of the same questions.

The American Civil Liberties Union, which represents breast cancer patients, researchers and professional groups that sued Myriad, argued before the U.S. Court of Appeals for the Federal Circuit that the Utah company cannot patent works of nature such as genes.

But Myriad said the materials it patents are taken out of their naturally occurring context and isolated from the body and, therefore, are not works of nature.

Richard Marsh, Myriad executive vice president and general counsel, said the Supreme Court decision in the related case was distinct from Myriads situation because it involved a process for testing drug levels versus Myriads claim over DNA material isolated from the body.

"In our case, isolated DNA, isolated from the human genome, is not found in nature," Marsh said in an interview after the court hearing.

But the ACLU argues that even out of the body, isolated DNA materials remain a product of nature and are ineligible for patenting. By patenting the materials, Myriad can deny other researchers the opportunity to do research on them and develop different tests for measuring the risk a woman carries of gene-related breast and ovarian cancer, the group said.

"We need to be sure that natural things and all natural laws are available to all mankind," Chris Hansen, an ACLU lawyer, told the appeals court, according to Bloomberg News. The Myriad claims "cover every conceivable form of DNA."

The ACLU position was backed by the Justice Department, which represented the government in place of the U.S. Patent and Trademark Office, which normally appears in such cases.

Justice Department lawyer Melissa Patterson said that isolation of a specific gene was insignificant. She likened it to extracting coal from the ground.

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Utah’s Myriad Genetics defends gene patent claims

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BOTHELL, Wash.--(BUSINESS WIRE)--

Seattle Genetics, Inc. (SGEN) today announced that its collaborator, Millennium: The Takeda Oncology Company, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, has received a positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for the conditional marketing authorization of ADCETRIS (brentuximab vedotin) for two indications: (1) the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma (HL) following autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30.

The positive opinion from CHMP and broad label recommendation is a key step in the European regulatory process for ADCETRIS and brings us closer to our goal of making this important new therapy globally available to patients with relapsed Hodgkin lymphoma or systemic ALCL, said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. If approved in the European Union, ADCETRIS will represent the first new therapeutic advance for relapsed Hodgkin lymphoma patients in several decades and further validates the potential of ADCs in the treatment of cancer.

The European Commission, which has the authority to approve medicines for use in the European Union, generally follows the recommendations of the CHMP and typically renders a final decision within three months of the CHMP opinion. If the CHMP recommendation is formally adopted by the European Commission, ADCETRIS would be approved for marketing in all 27 member states of the European Union.

European Commission approval will trigger two milestone payments, one for each indication, totaling $25 million to Seattle Genetics under the collaboration agreement between Seattle Genetics and Millennium: The Takeda Oncology Company. Seattle Genetics is also entitled to tiered double-digit royalties with percentages starting in the mid-teens and escalating to the mid-twenties based on net sales of ADCETRIS within Millenniums territories, subject to offsets for royalties paid by Millennium to third parties.

About ADCETRIS

ADCETRIS (brentuximab vedotin) is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS received accelerated approval from the U.S. Food and Drug Administration (FDA) in August 2011 for relapsed HL and sALCL.

Seattle Genetics and Millennium are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and the Takeda Group has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where the Takeda Group will be solely responsible for development costs.

About Seattle Genetics

Originally posted here:
Seattle Genetics Announces ADCETRIS® Receives Positive CHMP Opinion for Conditional Approval in European Union

Recommendation and review posted by Bethany Smith

The European Medicines Agency is recommending the first-ever approval of a gene therapy treatment in the EU, in a significant move for a type of treatment that has so far failed to deliver on its promise to cure diseases.

In a statement on Friday, the EMA said Glybera, made by Dutch company uniQure, should be approved across Europe for the treatment of an extremely rare disorder that leaves people unable to digest fat. The treatment consists of a gene that makes a protein to break down fat.

Gene therapy is an experimental technique that tries to cure diseases by replacing genes that don't work. It has never been approved in the U.S. and most trials over the past two decades have failed. China was the first country to approve a gene therapy treatment in 2003 for cancer.

Scientists have struggled to find ways to deliver the genes safely, often by using a harmless virus. There are also concerns that inserting a gene at the wrong spot could cause cancer or that the body's immune system might attack the new gene and the virus used to deliver it.

The EMA previously rejected Glybera three times but it was reconsidered at the request of the European Commission. The agency recommended approval under tough restrictions and will require the company to set up a registry to closely track patients. Previous trials of the treatment only tested it in 27 patients.

"It is only meant for patients with the greatest need," said Monika Benstetter, an EMA spokeswoman, explaining the gene therapy is intended for people with no other treatment options. She said only a handful of gene therapy treatments had been considered before one was recommended for approval but its manufacturer withdrew it before it was finalized.

Recommendations by the EMA are usually given final approval by the European Commission.

Patients with lipoprotein lipase deficiency, the inherited disease Glybera is intended to treat, often cannot eat a normal meal because it can lead to an extremely painful inflammation of the pancreas. Many patients with the disorder have a very restricted diet and only eat a fraction of their daily recommended calories. The condition affects only one to two people per million.

Jorn Aldag, CEO of uniQure, said the company was developing similar treatments for other diseases beyond rare conditions, including Parkinson's. "We believe that just like antibodies, gene therapy will one day be a mainstay in clinical practice," he said in a statement.

Benstetter said there are no other gene therapy treatments currently under consideration by the EMA and was unsure if the agency would get more applications based on Glybera's approval.

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Gene therapy for rare disease OK'd by EU regulator

Recommendation and review posted by Bethany Smith

By Naomi Kresge - 2012-07-20T19:16:23Z

Europe is on the cusp of approving the first gene therapy to be sold on the market in a western nation, a product from UniQure BV designed to treat a rare disease that disrupts fat production in the body.

The drug, called Glybera, won the backing of an advisory panel to the European Commission on its fourth attempt, the group said in a statement today. The Commission, which makes the final decision, usually follows the committees recommendation.

The move comes after 20 years of experimentation into a technology that in the past has been haunted by highly- publicized failures, including the death of 16-year-old Jessie Gelsinger in the U.S. in 1999. More recently, success in trials by Amsterdam-based UniQure and the U.S.-based companies Sangamo BioSciences Inc. (SGMO) and Neurologix Inc. (NRGXQ) are reviving the field.

This is good news for the field, definitely, said Savio Woo, a professor of genetics and genomic sciences at the Mount Sinai School of Medicine in New York. The technology has been really making a lot of progress, and a positive approval was more or less expected to come sometime.

UniQure began preparations a few weeks ago for meetings with the U.S. Food and Drug Administration to seek approval for Glybera, said Jorn Aldag, UniQures chief executive officer.

The treatment targets lipoprotein lipase deficiency, or LPLD, a rare fat-processing disorder that spurs severe or multiple pancreatitis attacks in about one or two people among every million in the population. The therapy is administered only once to be effective.

Glybera may have peak annual sales between 50 million euros ($61.1 million) and 300 million euros, depending on how its priced, Aldag said in an interview.

Its phenomenal because its the first gene therapy the EMA has approved, he said.

While two gene therapy products are sold in China, none are approved in Europe or the U.S., according to Mount Sinais Woo.

See the article here:
UniQure’s Glybera Wins EU Backing as First Gene Therapy

Recommendation and review posted by Bethany Smith

20 July 2012 Last updated at 11:11 ET By James Gallagher Health and science reporter, BBC News

Europe is on the cusp of approving a gene therapy for the first time, in what would be a landmark moment for the field.

Gene therapies alter a patient's DNA to treat inherited diseases passed from parent to child.

The European Medicines Agency has recommended a therapy for a rare genetic disease which leaves people unable to properly digest fats.

The European Commission will now make the final decision.

The idea of gene therapy is simple: if there is a problem with part of a patient's genetic code then replace that part of the code.

The reality has not been so easy. In one gene therapy trial a US teenager, Jesse Gelsinger, died, and other patients have developed leukaemia.

There are no gene therapies available outside of a research lab in Europe or the US.

The European Medicines Agency's Committee for Medicinal Products for Human Use has considered the use of Glybera to treat lipoprotein lipase deficiency.

One in a million people have the deficiency. They have damaged copies of a gene which is essential for breaking down fat.

More here:
Europe nears gene therapy first

Recommendation and review posted by Bethany Smith

The long-frustrated field of gene therapy is about to reach a major milestone: the first regulatory approval of a gene therapy treatment for disease in the West. The European Medicine Agency's Committee for Medicinal Products for Human Use said Friday that it is recommending approval of Glybera, a treatment for lipoprotein lipase deficiency manufactured by uniQure of Amsterdam. The European Commission generally follows the recommendations of the agency, and if it does so this time, the product could be available in all 27 members of the European Union by the end of the year.

Lipoprotein lipase deficiency is a rare disease, a so-called orphan disease, that affects one or two of every million people. As the name suggests, it is the result of a deficiency of an enzyme called lipoprotein lipase. This enzyme breaks down large, fat-carrying molecules, called chylomicrons, that circulate in the blood following meals. When the enzyme is defective, the chylomicrons accumulate, turning the blood almost milky white and blocking small blood vessels, producing severe inflammation of the pancreas -- called pancreatitis. The severe pain typically requires hospitalization. There is currently no treatment for the disease other than regulation of the diet.

Glybera is an active form of lipoprotein lipase that is injected into the patient's legs in a series of shots at one sitting. Clinical trials conducted in 27 people by Dr. Daniel Gaudet of the University of Montreal show that the injections are long-lasting and provide at least partial control of lipoprotein lipase deficiency with no apparent adverse effects. Bouts of pancreatitis are fewer and less severe following treatment.

The European agency had rejected Glybera three times in the past year, citing insufficient evidence of benefit, before unexpectedly reversing its decision and recommending approval. The approval decision was for patients with the most severe form of the disease, and the agency said that the company would be required to monitor patients and provide data to regulators.

UniQure said it will apply for approval in the United States, but is not sure when.

The only previous approval of a gene therapy product is a cancer treatment that has been approved in China.

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First gene therapy in West, for a rare disease, on the horizon

Recommendation and review posted by Bethany Smith

The European Medicines Agency is recommending the first-ever approval of a gene therapy treatment in the EU, in a significant move for a type of treatment that has so far failed to deliver on its promise to cure diseases.

In a statement on Friday, the EMA said Glybera, made by Dutch company uniQure, should be approved across Europe for the treatment of an extremely rare disorder that leaves people unable to digest fat. The treatment consists of a gene that makes a protein to break down fat.

Gene therapy is an experimental technique that tries to cure diseases by replacing genes that don't work. It has never been approved in the U.S. and most trials over the past two decades have failed. China was the first country to approve a gene therapy treatment in 2003 for cancer.

Scientists have struggled to find ways to deliver the genes safely, often by using a harmless virus. There are also concerns that inserting a gene at the wrong spot could cause cancer or that the body's immune system might attack the new gene and the virus used to deliver it.

The EMA previously rejected Glybera three times but it was reconsidered at the request of the European Commission. The agency recommended approval under tough restrictions and will require the company to set up a registry to closely track patients. Previous trials of the treatment only tested it in 27 patients.

"It is only meant for patients with the greatest need," said Monika Benstetter, an EMA spokeswoman, explaining the gene therapy is intended for people with no other treatment options. She said only a handful of gene therapy treatments had been considered before - one was recommended for approval but its manufacturer withdrew it before it was finalized.

Recommendations by the EMA are usually given final approval by the European Commission.

Patients with lipoprotein lipase deficiency, the inherited disease Glybera is intended to treat, often cannot eat a normal meal because it can lead to an extremely painful inflammation of the pancreas. Many patients with the disorder have a very restricted diet and only eat a fraction of their daily recommended calories. The condition affects only one to two people per million.

Jorn Aldag, CEO of uniQure, said the company was developing similar treatments for other diseases beyond rare conditions, including Parkinson's. "We believe that just like antibodies, gene therapy will one day be a mainstay in clinical practice," he said in a statement.

Benstetter said there are no other gene therapy treatments currently under consideration by the EMA and was unsure if the agency would get more applications based on Glybera's approval.

Continued here:
First ever gene therapy treatment recommended by European regulator

Recommendation and review posted by Bethany Smith

LONDON (AP) -- The European Medicines Agency is recommending the first-ever approval of a gene therapy treatment in the EU, in a significant move for a type of treatment that has so far failed to deliver on its promise to cure diseases.

In a statement on Friday, the EMA said Glybera, made by Dutch company uniQure, should be approved across Europe for the treatment of an extremely rare disorder that leaves people unable to digest fat. The treatment consists of a gene that makes a protein to break down fat.

Gene therapy is an experimental technique that tries to cure diseases by replacing genes that don't work. It has never been approved in the U.S. and most trials over the past two decades have failed. China was the first country to approve a gene therapy treatment in 2003 for cancer.

Scientists have struggled to find ways to deliver the genes safely, often by using a harmless virus. There are also concerns that inserting a gene at the wrong spot could cause cancer or that the body's immune system might attack the new gene and the virus used to deliver it.

The EMA previously rejected Glybera three times but it was reconsidered at the request of the European Commission. The agency recommended approval under tough restrictions and will require the company to set up a registry to closely track patients. Previous trials of the treatment only tested it in 27 patients.

"It is only meant for patients with the greatest need," said Monika Benstetter, an EMA spokeswoman, explaining the gene therapy is intended for people with no other treatment options. She said only a handful of gene therapy treatments had been considered before one was recommended for approval but its manufacturer withdrew it before it was finalized.

Recommendations by the EMA are usually given final approval by the European Commission.

Patients with lipoprotein lipase deficiency, the inherited disease Glybera is intended to treat, often cannot eat a normal meal because it can lead to an extremely painful inflammation of the pancreas. Many patients with the disorder have a very restricted diet and only eat a fraction of their daily recommended calories. The condition affects only one to two people per million.

Jorn Aldag, CEO of uniQure, said the company was developing similar treatments for other diseases beyond rare conditions, including Parkinson's. "We believe that just like antibodies, gene therapy will one day be a mainstay in clinical practice," he said in a statement.

Benstetter said there are no other gene therapy treatments currently under consideration by the EMA and was unsure if the agency would get more applications based on Glybera's approval.

Excerpt from:
European regulator: Gene therapy treatment OK

Recommendation and review posted by Bethany Smith

An ongoing legal battle over gene patents has led many scientists to ask whether such claims help or hinder research. That question will be debated once more on 20 July when Myriad Genetics, a diagnostic company in Salt Lake City, Utah, returns to the US courts to argue that its patents on theBRCA1 and BRCA2 gene variants linked to inherited breast and ovarian cancer are valid. Currently, the patents give Myriad exclusive rights to conduct diagnostic tests on the genes. The judges are expected to issue an opinion by late summer. The case is important because thousands of genes have been patented in the United States, and no one is sure what will happen if the judges rule Myriad's patents invalid. Natureexamines what the Myriad case means to biotechnology and genetic medicine.

An argument over whether isolated DNA is patentable is at the centre of a US court case on existing gene patents.

Alfred Pasieka/Getty Images

In the United States, 'laws of nature' are not able to be patented, along with abstract ideas. The argument against Myriad's patents centres on whether isolated DNA is the same as native DNA, which is defined as a law of nature. If the court decides that the patents are invalid, that ruling would reverse more than 20 years of precedent, during which companies and academic researchers have patented thousands of genes. Some of these genes form the basis of diagnostic tests that determine when someone might respond well to a given therapy, or whether theyre at risk of a disease or a drug side effect, for example.

Although the courtsupheld Myriads patents in July 2011, the Supreme Court ordered the Appellate Court to reconsider the case in light of a ruling in March 2012 against the diagnostics company Prometheus Laboratories in San Diego, California (see 'US Supreme Court upends diagnostics patents'). Prometheus held patents on a method of determining drug dosage for a patient on the basis of the amount of certain components in their blood. According to the judge, this test merely reiterated a law of nature the relationship between the concentration of blood components and the likelihood that a drug dosage will be harmful or ineffective. Legal briefs recently filed by the US Department of Justice urge the judges to consider whether Myriad's patents 'tie up' the future use of laws of nature, as decided in the case against Prometheus.

Yes, according to the American Civil Liberties Union (ACLU) in New York, a legal group that represents the plaintiffs in the case, who include researchers, scientific societies and women with cancer. By claiming a law of nature, they can stop every other lab from performing tests, even with different testing methods, says ACLU attorney Sandra Park. Although there are some 8,000 publications on BRCA genes, which testify to the fact that research on the genes is ongoing, Myriad prevented at least five researchers who are some of the plaintiffs in this case from testing women in-house as part of their academic studies. Its within [Myriads] power to give licences to scientists, Park says, but the way theyve exercised their rights shows that they are intent on maintaining a monopoly. Legal briefs filed by DNA co-discoverer James Watson urge the judges to consider whether the patent leaves the public free to study the genes encoding BRCA1 and BRCA2.

Venture capitalists would be reluctant to invest in a small biotechnology firm if there was no secure patent protection, says Hans Sauer, an intellectual-property lawyer at the Biotechnology Industry Organization in Washington DC, a trade association for biotech companies that has filed a brief in favour of Myriad. Its already quite hard to get good patent protection in the area of personalized medicine, and theMyriadcase adds another layer of complexity, he notes. Companies will still be able to patent genes if Myriad loses its case, but the patents might need to be more narrowly defined and so might not protect companies as effectively, he predicts. For example, a patent might protect a kit that detects specific mutations within a gene associated with causing colon cancer, the result of which helps physicians to tailor their patients treatment. The issue with narrower patents, however, is that other companies can design tests that detect different mutations, or they could develop kits that detect the same mutations using different reagents.

Scientists tend to ignore patent claims on genes or genetic diagnostic methods because the patent-holding companies generally reserve litigation for individuals who seek to profit from their product, Sauer says. Researchers have occaisonally been issued cease and desist letters to stop them working on patented genes but these cases rarely, if ever, result in lawsuits. One way to increase researchers security might be to explicitly allow experimental use exceptions, as occurs in European patent law. It works well in other countries, says Sauer, so I dont see why it wouldnt work here.

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The great gene-patent debate

Recommendation and review posted by sam

By Tony Daltorio - July 20, 2012 | Tickers: A, BMY, LLY, QGEN, RHHBY.PK | 0 Comments

Tony is a member of The Motley Fool Blog Network -- entries represent the personal opinions of our bloggers and are not formally edited.

Nearly every investor has heard about the patent cliff facing the major pharmaceutical companies. But there is another, quiet revolution occurring in the pharmaceutical sector right nowwhich very well may change its current business model drastically. That revolution is 'personalized medicine.'

Personalized medicine is the result of advances in genetics and molecular biology. While still in its early stages, it promises improvements in patients' treatment while at the same time reducing healthcare expenditures. It does so through molecular biology and the use of diagnostic tools, which is pivotal to determine whether an individual patient will benefit from a particular drug used to treat a specific disease such as cancer.

A recent advance in personalized medicine happened when the U.S. Food and Drug Administration approved a test called Therascreen from Qiagen NV (NASDAQ: QGEN) that will be used in conjunction with the drug Erbitux (used for colorectal cancer) that ismarketed by Eli Lilly (NYSE: LLY) and Bristol-Myers Squibb (NYSE: BMY). The test will allow the two companies to identify the 60 percent of patients who do not have a mutation in the KRAS gene and will benefit from the drug, thus avoiding giving the drug to patients who do have the mutation and will not benefit.

Based on history, this should be a big boost for sales of Erbitux. AstraZeneca's lung cancer drug Iressa, launched in 2002, had little success because of its high failure rate. But after a diagnostic test was developed in 2009, sales began to grow as the 10 percent of patients (with an EGFR mutation) helped by the drug were identified.

Theokayfor Therascreen is a milestone since the FDA has only approved a handful of drugs with companion tests over the past decade. Perhaps best known is Herceptin from Roche ADR (NASDAQOTH: RHHBY.PK), which is given to the quarter of women with breast cancer that have a so-called over-expression of the Her2 gene. The diagnostic test is a joint venture of Genentech, now owned by Roche, and the Danish diagnostics company Dako which is now owned by Agilent Technologies (NYSE: A). Agilent bought Dako in June for $2.2 billion in cash from the Swedish private equity firm EQT.

The recent FDA approval underscores the growing importance of 'companion diagnostics' used to analyze a patient's genetics to determine whether that patient will benefit from a specific drug. This may change pharmaceutical companies' entire business models to include companion diagnostics with all of their major drugs on the market. For example, Roche says that 60 percent of the drugs in its current pipeline are linked to a companion diagnostic.

Think about it...in the future, such diagnostic testing will nearly eliminate failure of drugs to work in certain patients and those costly side effects will be avoided because drugs will only be given to patients where the genetics have been determined to be compatible with the drug.

Even though some drug companies are keeping the companion diagnostics in house, the advancement of personalized medicine is potentially great news for companies in the diagnostics business such as Agilent Technologies, which is expanding its life sciences business into a fourth division at the firm, and Qiagen, which already manufactures 30 companion diagnostic tests.

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Personalized Medicine Plus Diagnostics Equals Profits for Investors

Recommendation and review posted by sam

With the new tools, researchers can compare patterns of drug activity and gene expression, not only to each other but also to other patterns of interest.

The newly updated software, called CellMiner, was built for use with the NCI-60, one of the most widely utilized collections of cancer cell samples employed in the testing of potential anti-cancer drugs. The tools, available free, provide rapid access to data from 22,379 genes catalogued in the NCI-60 and from 20,503 previously analyzed chemical compounds, including 102 U.S. Food and Drug Administration-approved drugs.

The study, written by the scientists that developed the tools at the National Cancer Institute (NCI), part of the National Institutes of Health, appeared in the July 16, 2012, issue of Cancer Research.

"Previously you would have to hire a bioinformatics team to sort through all of the data, but these tools put the entire database at the fingertips of any researcher," explained Yves Pommier, M.D., Ph.D., of the NCI's Center for Cancer Research. "These tools allow researchers to analyze drug responses as well as make comparisons from drug to drug and gene to gene."

Genomic sequencing and analysis have become increasingly important in biomedicine, but they are yielding data sets so vast that researchers may find it difficult to access and compare them. As new technologies emerge and more data are generated, tools to facilitate the comparative study of genes and potentially promising drugs will be of even greater importance. With the new tools, researchers can compare patterns of drug activity and gene expression, not only to each other but also to other patterns of interest. CellMiner allows the input of large quantities of genomic and drug data, calculates correlations between genes and drug activity profiles, and identifies correlations that are statistically significant. Its data integration capacities are easier, faster, and more flexible than other available methods, and these tools can be adapted for use with other collections of data.

Researchers looking at a particular drug can use the tools to access data from previous experiments done on that drug and analyze how the drug relates to other drugs and various gene profiles. As a case example for this study, the researchers compared drug activity levels and gene expression patterns from previous research to identify an investigational compound, called NSC732298, which is not currently being studied for colon cancer, but could be a potential therapy for the disease based on a CellMiner gene-drug match. In the same exercise, the researchers were able to identify that a second investigational drug that is being tested for colon cancer, called selumetinib, might also be effective against melanoma.

"We're looking forward to seeing how other people are going to use this tool to look at gene co-regulation, regulation of gene expression, and the relationship between gene expression and cancer," said Pommier.

This work was supported by NCI's Center for Cancer Research and Division of Cancer Treatment and Diagnosis under intramural project number ZIA BC 006150.

Related Tool Link http://discover.nci.nih.gov/cellminer

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Matching Cancer Drugs with Gene Targets

Recommendation and review posted by Bethany Smith

ScienceDaily (July 19, 2012) The entire genomes of 91 human sperm from one man have been sequenced by Stanford University researchers. The results provide a fascinating glimpse into naturally occurring genetic variation in one individual, and are the first to report the whole-genome sequence of a human gamete -- the only cells that become a child and through which parents pass on physical traits.

"This represents the culmination of nearly a decade of work in my lab," said Stephen Quake, PhD, the Lee Otterson Professor in the School of Engineering and professor of bioengineering and of applied physics. "We now have devices that will allow us to routinely amplify and sequence to a high degree of accuracy the entire genomes of single cells, which has far-ranging implications for the study of cancer, infertility and many other disorders."

Quake is the senior author of the research, published July 20 in Cell. Graduate student Jianbin Wang and former graduate student H. Christina Fan, PhD, now a senior scientist at ImmuMetrix, share first authorship of the paper.

Sequencing sperm cells is particularly interesting because of a natural process called recombination that ensures that a baby is a blend of DNA from all four of his or her grandparents. Until now, scientists had to rely on genetic studies of populations to estimate how frequently recombination had occurred in individual sperm and egg cells, and how much genetic mixing that entailed.

"Single-sperm sequencing will allow us to chart and understand how recombination differs between individuals at the finest scales. This is an important proof of principle that will allow us to study both fundamental dynamics of recombination in humans and whether it is involved in issues relating to male infertility," said Gilean McVean, PhD, professor of statistical genetics at the Wellcome Trust Centre for Human Genetics. McVean was not involved in the research.

The Stanford study showed that the previous, population-based estimates were, for the most part, surprisingly accurate: on average, the sperm in the sample had each undergone about 23 recombinations, or mixing events. However, individual sperm varied greatly in the degree of genetic mixing and in the number and severity of spontaneously arising genetic mutations. Two sperm were missing entire chromosomes. The study has long-ranging implication for infertility doctors and researchers.

"For the first time, we were able to generate an individual recombination map and mutation rate for each of several sperm from one person," said study co-author Barry Behr, PhD, HCLD, professor of obstetrics and gynecology and director of Stanford's in vitro fertilization laboratory. "Now we can look at a particular individual, make some calls about what they would likely contribute genetically to an embryo and perhaps even diagnose or detect potential problems."

Most cells in the human body have two copies of each of 23 chromosomes, and are known as "diploid" cells. Recombination occurs during a process called meiosis, which partitions a single copy of each chromosome into a sperm (in a man) or egg (in a woman) cell. When a sperm and an egg join, the resulting fertilized egg again has a full complement of DNA.

To ensure an orderly distribution during recombination, pairs of chromosomes are lined up in tight formation along the midsection of the cell. During this snug embrace, portions of matching chromosomes are sometimes randomly swapped. The process generates much more genetic variation in a potential offspring than would be possible if only intact chromosomes were segregated into the reproductive cells.

"The exact sites, frequency and degree of this genetic mixing process is unique for each sperm and egg cell," said Quake, "and we've never before been able to see it with this level of detail. It's very interesting that what happens in one person's body mirrors the population average."

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Entire genetic sequence of individual human sperm determined

Recommendation and review posted by Bethany Smith

RYE BROOK, NY--(Marketwire -07/19/12)- As part of a fundamental commitment to support physicians in the management of cancer, CBLPath announces today its launch of in-house NRAS Mutation Analysis testing. This molecular assay screens for clinically relevant genetic mutations that may be present in cases of colorectal cancer, melanoma and thyroid cancer, thus helping oncologists make an accurate diagnosis and the most appropriate treatment decisions for affected patients.

"Our new polymerase chain reaction, or PCR-based test uses the latest sequencing technology to detect NRAS genetic aberrations in a timely and accurate manner, aiding molecular classification of disease and consequently impacting patient prognosis and therapeutic efficacy," said Co-CEO and Chief Medical Officer, Dr. Carlos D. Urmacher, FCAP, FASCP.

"We're pleased to add NRAS to our powerful arsenal of biomarker-centered diagnostics that are advancing the practice of personalized medicine. It's truly a 'win-win' for oncologists, who can provide better medicine, faster with our testing and for their patients who receive customized care and targeted treatment based on their individual molecular profiles."

The NRAS gene (Neuroblastoma RAS Viral Oncogene Homolog Gene) encodes the NRAS enzyme, which is member of RAS family of proteins. (RAS is an abbreviation for Rat sarcoma, where these proteins were first found.) RAS family members belong to a class of proteins called small GTPases, which carry out a pivotal role in many vital biological processes within the human body, acting as molecular switches to transmit signals within cells. NRAS itself plays a key part in the MAPK (mitogen-activated protein kinase) cellular signaling pathway, which is involved in the regulation of cell growth, differentiation and survival.

CBLPath's NRAS sequencing assay detects variation in codons 12, 13 and 61 of the NRAS oncogene that may be present in colorectal cancer, melanoma and thyroid cancer patients.

In patients with metastatic colorectal cancer, the occurrence of NRAS mutations may be predictive of non-response to anti-EGFR (epidermal growth factor receptor) therapies such as cetuximab and panitumumab. The presence of activating mutations in the cell signaling pathway has been shown to impact the body's ability to respond to these cancer treatments.

In melanoma patients, NRAS mutations may indicate that a tumor will respond favorably to drugs that target genes downstream of NRAS in the MAPK cell signaling pathway, including RAF and MEK.

In thyroid cancer patients, RAS genetic mutations -- particularly NRAS -- have been detected in up to 40% of follicular thyroid carcinomas and up to 10% of papillary thyroid carcinomas. These genetic variants are also found frequently in follicular adenomas. Accordingly, a patient's RAS mutation status must be correlated with morphologic and clinical findings. This is especially important for patients with follicular thyroid tumors, as RAS mutations may be associated with more aggressive disease.

To speak with your local CBLPath representative about ordering NRAS Mutation Analysis testing, call 877.225.7284. To see the company's entire array of tests, visit http://www.CBLPath.com and click Test Menu.

About CBLPathCBLPath is a national specialty lab with a unique leadership position in the convergence of anatomic, molecular and digital pathology. Beginning from a clinical perspective, we harness molecular testing and digital pathology on an anatomic pathology foundation. CBLPath is committed to helping our clients deliver better medicine, faster. At our core are pathologists; excited about technology and innovation and its promise of helping patients. Through the Best Practice Partnership Program we help our pathologist-clients effectively compete against centralized reference laboratories, grow their Practice and remain independent -- Keeping Medicine Local. We provide our subspecialty physician clients comprehensive diagnostics and timely, accurate reports enabling the best patient care. For more about the company, please visit http://www.CBLPath.com.

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CBLPath Bolsters Cancer Management With New NRAS Gene Mutation Analysis Assay

Recommendation and review posted by Bethany Smith