Archive for the ‘Gene Therapy Research’ Category

In a development scientists are calling a "tour de force," researchers have reconstructed the genome of a fetus using DNA samples from the parents.

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Amid ongoing reports of burning eyes and emergency injuries, the makers of a popular contact lens solution have failed to adequately warn consumers about the dangers of using the product improperly, a patient safety group says.

Because their technique did not require an invasive test to take samples from the fetus itself, it's an important step toward what could become a low-risk way to identify genetic disorders early in development, experts say.

Currently, "when genetic testing is done, it's done for just a few diseases," said lead author Dr. Jay Shendure, an associate professor of genome sciences at the University of Washington.

A test based on the new technique could detect the roughly 3,000 conditions known as Mendelian disorders, each of which are the result of a single mutated gene, Shendure said. Huntington's disease, hemophilia and sickle-cell anemia fall into this category.

While each of these disorders is relatively rare, together they affect about 1 percent of births, Shendure said.

"This is amazing," said Dr. Ada Hamosh, director of the Institute of Genetic Medicine at the Johns Hopkins University School of Medicine, of the findings. "On the other hand, in no way is this ready for prime time," said Hamosh, who was not involved with the research.

Shendure and colleagues put together the fetal genome using a saliva sample from the father, and a sample of blood plasma from the mother. About 13 percent of the DNA found outside of cells in a pregnant woman's body belongs to her fetus.

They sequenced the regions of DNA they were aiming for with 98.2 percent accuracy.

Originally posted here:
New testing could help spot genetic disorders

By contrast, the scientists say their new test would identify far more conditions, caused by genetic errors.

However, they warned it raised many ethical questions because the results could be used as a basis for abortion.

These concerns were last night amplified by pro-life campaigners, who said widespread use of such a test would inevitably lead to more abortions.

The American scientists were able to map the babys genetic code principally from tiny traces free-floating DNA, which makes its way into the mothers blood.

Blood sample DNA from the mother was also studied as well as DNA extracted from the father's saliva.

Fitting pieces of the genetic jigsaw together, scientists in the US were able to reconstruct the entire genetic code of an unborn baby boy.

They were then able to see what spontaneous genetic mutations had arisen.

Such natural mutations - called de novo mutations - are responsible for the majority of genetic defects.

By checking their prediction of the babys genetic code with actual DNA taken after the birth, the team from the University of Washington in Seattle, found they were able to identify 39 of 44 such mutations in the child.

De novo mutations are thought to play a role in a number of complex conditions such as autism and schizophrenia.

More here:
Babies could be tested for 3,500 genetic faults

ScienceDaily (June 5, 2012) Using a noninvasive test on maternal blood that deploys a novel biochemical assay and a new algorithm for analysis, scientists can detect, with a high degree of accuracy, the risk that a fetus has the chromosomal abnormalities that cause Down syndrome and a genetic disorder known as Edwards syndrome. The new approach is more scalable than other recently developed genetic screening tests and has the potential to reduce unnecessary amniocentesis or CVS.

Two studies evaluating this approach are available online in advance of publication in the April issue of the American Journal of Obstetrics & Gynecology (AJOG).

Diagnosis of fetal chromosomal abnormalities, or aneuploidies, relies on invasive testing by chorionic villous sampling or amniocentesis in pregnancies identified as high-risk. Although accurate, the tests are expensive and carry a risk of miscarriage. A technique known as massively parallel shotgun sequencing (MPSS) that analyzes cell-free DNA (cfDNA) from the mother's plasma for fetal conditions has been used to detect trisomy 21 (T21) pregnancies, those with an extra copy of chromosome 21 that leads to Down syndrome, and trisomy 18 (T18), the chromosomal defect underlying Edwards syndrome. MPSS accurately identifies the conditions by analyzing the entire genome, but it requires a large amount of DNA sequencing, limiting its clinical usefulness.

Scientists at Aria Diagnostics in San Jose, CA developed a novel assay, Digital Analysis of Selected Regions (DANSR), which sequences loci from only the chromosomes under investigation. The assay requires 10 times less DNA sequencing than MPSS approaches.

In the current study, the researchers report on a novel statistical algorithm, the Fetal-fraction Optimized Risk of Trisomy Evaluation (FORTE), which considers age-related risks and the percentage of fetal DNA in the sample to provide an individualized risk score for trisomy. Explains author Ken Song, MD, "The higher the fraction of fetal cfDNA, the greater the difference in the number of cfDNA fragments originating from trisomic versus disomic [normal] chromosomes and hence the easier it is to detect trisomy. The FORTE algorithm explicitly accounts for fetal fraction in calculating trisomy risk."

To test the performance of the DANSR/FORTE assay, Dr. Song and his colleagues evaluated a set of subjects consisting of 123 normal, 36 T21, and 8 T18 pregnancies. All samples were assigned FORTE odd scores for chromosome 18 and chromosome 21. The combination of DANSR and FORTE correctly identified all 36 cases of T21 and 8 cases of T18 as having a greater than 99% risk for each trisomy in a blinded analysis. There was at least a 1,000 fold magnitude separation in the risk score between trisomic and disomic samples.

In a related study, researchers from the Harris Birthright Research Centre for Fetal Medicine, Kings College Hospital, University of London and the University College London Hospital, University College London, provided 400 maternal plasma samples to Aria for analysis using the DANSR assay with the FORTE algorithm. The subjects were all at risk for aneuploidies, and they had been tested by chorionic villous sampling. The analysis distinguished all cases of T21 and 98% of T18 cases from euploid pregnancies. In all cases of T21, the estimated risk for this aneuploidy was greater than or equal to 99%, whereas in all normal pregnancies and those with T18, the risk score for T21 was less than or equal to 0.01%.

"Combining the DANSR assay with the FORTE algorithm provides a robust and accurate assessment of fetal trisomy risk," says Dr. Song. "Because DANSR allows analysis of specific genomic regions, it could be potentially used to evaluate genetic conditions other than trisomy. The incorporation of additional risk information, such as from ultrasonography, into the FORTE algorithm warrants investigation."

Kypros H. Nicolaides, MD, senior author of the University of London study, suggests that fetal trisomy evaluation with cfDNA testing will inevitably be introduced into clinical practice. "It would be useful as a secondary test contingent upon the results of a more universally applicable primary method of screening. The extent to which it could be applied as a universal screening tool depends on whether the cost becomes comparable to that of current methods of sonographic and biochemical testing."

Dr. Nicolaides also notes that the plasma samples were obtained from high-risk pregnancies where there is some evidence of impaired placental function. It would also be necessary to demonstrate that the observed accuracy with cfDNA testing obtained from the investigation of pregnancies at high-risk for aneuploidies is applicable to the general population where the prevalence of fetal trisomy 21 is much lower. "This may well prove to be the case because the ability to detect aneuploidy with cfDNA is dependent upon assay precision and fetal DNA percentage in the sample rather than the prevalence of the disease in the study population," he concludes.

See the article here:
Noninvasive genetic test for Down syndrome and Edwards syndrome highly accurate

New Test Uses Mom's Blood, Dad's Saliva to Determine Baby's Genetic Code

June 6, 2012 -- Samples of blood and saliva from parents-to-be may help identify thousands of genetic disorders in fetuses soon after conception without invasive testing, researchers say.

In a study published today in the journal Science Translational Medicine, researchers from the University of Washington report that they were able to determine the complete DNA sequence of two babies in the womb by analyzing blood samples from the mother and saliva samples from the father.

Genetic predictions were confirmed once the babies were born by analyzing umbilical cord blood collected at birth.

The test is not ready for use yet. Although cost and technological challenges remain, the research could lead to a simple non-invasive test to identify more than 3,000 disorders caused by single-gene mutations, says study co-author Jay Shendure, MD, PhD.

"Many of these diseases are so rare that most people have never heard of them, but collectively they affect around 1% of births," Shendure tells WebMD.

Only a few genetic disorders, including Down syndrome, are screened for during pregnancy. They use invasive and potentially risky procedures such as amniocentesis and chorionic villus sampling.

The search is underway for less invasive tests using blood samples from pregnant women instead of fluid from the uterus. That's based on the recognition that fetal DNA is present in the blood of pregnant women at varying concentrations during pregnancy.

In the newly published study, researchers confirmed that blood taken from an expectant mother about 18 weeks into her pregnancy and saliva specimens taken from the father contained enough genetic information to map the DNA code of the developing fetus.

The finding was later confirmed in another expectant couple with blood taken from the mother even earlier in her pregnancy.

Read more from the original source:
Blood Test May Spot Genetic Disease in Fetuses

Editor's Choice Main Category: Smoking / Quit Smoking Also Included In: Genetics Article Date: 06 Jun 2012 - 14:00 PDT

Current ratings for: 'Genetics Alter Ability To Quit Smoking'

The finding could pave the way for health care providers to offer a more individualized therapy in the future to assist people in their quest to stop smoking.

NIDA Director Nora D. Volkow, M.D. declares:

The researchers decided to base their investigation on a cluster of nicotinic receptor genes, namely CHRNA5-CHRNA3-CHRNB4, as previous study have shown that these genes are involved in nicotine dependence and heavy smoking.

Using data from an earlier study, they demonstrated that people with the high-risk nicotinic receptor gene cluster ceased to smoke, on average, 2 years later than those with the low-risk genes. The delay was due to the fact that those with the high-risk gene cluster's tobacco consumption was heavier.

A subsequent clinical trial confirmed that when treated with placebo, the likelihood of failing in their attempts to stop smoking was higher in the high-risk gene group than in those with the low-risk genes, whereas nicotine cessation drugs, like nicotine replacement therapies or bupropion, increased the high-risk group's chance of successfully quitting by a three-fold after the end of the treatment when compared with placebo. This means these drugs prove particularly beneficial in this population group.

First author, Li-Shiun Chen, M.D., of the Washington University School of Medicine in St. Louis explained:

In the US, smoking is the single most preventable cause of disease, disability and death according to the Centers for Disease Control and Prevention (CDP). 440,000 deaths from smoking or exposure to secondhand smoke could be prevented each year, which translated to about 1 in 5 deaths in the US overall, whilst 8.6 million suffer from a serious smoking-related illness, and even though these health costs are well-documented, there are still more than 46 million adult smokers in the U.S.

Written By Petra Rattue Copyright: Medical News Today Not to be reproduced without permission of Medical News Today

Read the rest here:
Genetics Alter Ability To Quit Smoking

SALT LAKE CITY, June 6, 2012 (GLOBE NEWSWIRE) -- Myriad Genetics announced today that the Company is the honorable recipient of the 2012 Charles R. Smart Visionary Award from the American Cancer Society's Salt Lake City office, a part of the Great West Division. This award is presented annually at the Society's Legacy & Leadership event to recognize organizations that have made extraordinary efforts in the fight against cancer.

Myriad and its employees are dedicated to saving lives and improving the quality of life of patients with cancer. In addition to its life-saving molecular diagnostic tests, Myriad is a local community leader with the American Cancer Society in the fight against cancer. The Company and its employees have played an important role in events to benefit the American Cancer Society including the Hope Gala, Making Strides Against Breast Cancer and Relay for Life.

"We are deeply honored to receive the Charles R. Smart Visionary award," said Peter Meldrum, President and Chief Executive Officer of Myriad Genetics. "Myriad and the American Cancer Society share the goal of improving the quality of life for patients with cancer. Everyday our activities are guided by this mission and therefore we have been pleased to offer our financial support, leadership involvement and volunteer participation to this cause."

The late Dr. Charles R. Smart, a lifelong resident of Utah, was a pioneer in the study of cancer. Dr. Smart spent more than 35 years focused on establishing computerized cancer research and was the founder of the Utah Cancer Registry, a population based registry that has been doing systematic cancer surveillance in the state since 1966.

About Myriad Genetics

Myriad Genetics, Inc., an internationally recognized leader in molecular diagnostics, is dedicated to making a difference in patient's lives through the discovery and commercialization of transformative tests to assess a person's risk of developing disease, guide treatment decisions and assess risk of disease progression and recurrence. Myriad's portfolio of molecular diagnostic tests are based on an understanding of the role genes play in human disease and were developed with a commitment to improving an individual's decision making process for monitoring and treating disease. Myriad is focused on strategic directives to introduce new products, including companion diagnostics, as well as expanding internationally. For more information on how Myriad is making a difference, please visit the Company's website: http://www.myriad.com

Myriad, the Myriad logo, BRACAnalysis, Colaris, Colaris AP, Melaris, TheraGuide, Prezeon, OnDose, Panexia and Prolaris are trademarks or registered trademarks of Myriad Genetics, Inc. in the United States and foreign countries. MYGN-G

Safe Harbor Statement

This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the Company's strategic directives under the caption "About Myriad Genetics". These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that sales and profit margins of our existing molecular diagnostic tests and companion diagnostic services may decline or will not continue to increase at historical rates; the risk that we may be unable to expand into new markets outside of the United States; the risk that we may be unable to develop or achieve commercial success for additional molecular diagnostic tests and companion diagnostic services in a timely manner, or at all; the risk that we may not successfully develop new markets for our molecular diagnostic tests and companion diagnostic services, including our ability to successfully generate revenue outside the United States; the risk that licenses to the technology underlying our molecular diagnostic tests and companion diagnostic services and any future products are terminated or cannot be maintained on satisfactory terms; risks related to delays or other problems with manufacturing our products or operating our laboratory testing facilities; risks related to public concern over genetic testing in general or our tests in particular; risks related to regulatory requirements or enforcement in the United States and foreign countries and changes in the structure of healthcare payment systems; risks related to our ability to obtain new corporate collaborations and acquire new technologies or businesses on satisfactory terms, if at all; risks related to our ability to successfully integrate and derive benefits from any technologies or businesses that we acquire; the development of competing tests and services; the risk that we or our licensors may be unable to protect the proprietary technologies underlying our tests; the risk of patent-infringement and invalidity claims or challenges of our patents; risks of new, changing and competitive technologies and regulations in the United States and internationally; and other factors discussed under the heading "Risk Factors" contained in Item 1A in our most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. All information in this press release is as of the date of the release, and Myriad undertakes no duty to update this information unless required by law.

Original post:
Myriad Genetics Receives the Charles R. Smart Visionary Award From the American Cancer Society(R)

Public release date: 5-Jun-2012 [ | E-mail | Share ]

Contact: David Eve celltransplantation@gmail.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Tampa, Fla. (June 5 , 2012) A study characterizing the multipotency and transplantation value of olfactory stem cells, as well as the ease in obtaining them, has been published in a recent issue of Cell Transplantation (20:11/12), now freely available on-line at http://www.ingentaconnect.com/content/cog/ct/.

"There is worldwide enthusiasm for cell transplantation therapy to repair failing organs," said study lead author Dr. Andrew Wetzig of the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia. "The olfactory mucosa of a patient's nose can provide cells that are potentially significant candidates for human tissue repair."

According to the study authors, olfactory neural stem cells can be derived from a patient's own cells, they are readily available by a minimally invasive biopsy technique, and they can be expanded in vitro. The cells are plentiful because the olfactory epithelium undergoes neurogenesis and continual replacement of sensory neurons throughout adult life.

"Using the rat as our animal model source, we examined the basic aspects of olfactory neural stem cell biology and its potential for self-renewal and phenotypic expression in various circumstances," said Dr. Wetzig. "Previously, we found that they have performed well in pre-clinical models of disease and transplantation and seem to emulate a wound healing process where the cells acquire the appropriate phenotype in an apparently orderly fashion over time."

The researchers concluded that the olfactory neurospheres contain stem cells whose capacity for differentiation is triggered by signals from the immediate environmental niche.

"Stem cell numbers were shown to be enriched by our culture methods," explained Dr. Wetzig. "We also demonstrated that when adult olfactory stem cells are transplanted into an environmental niche different from that of their origin, they demonstrate multipotency by acquiring the phenotype of the resident cells."

"This study highlights another potential source of stem cells that has shown some degree of promise in a number of studies" said Dr. John Sladek, professor of neurology and pediatrics at the University of Colorado School of Medicine. "Their relatively easy accessibility and multipotent properties are important factors that could rank these cells competitively with other stem cells thus giving them a potential impact as an excellent source for cell therapy".

###

Read this article:
The potential impact of olfactory stem cells as therapy reported in Cell Transplantation

Global medical products and services company, Baxter International, Inc. ( BAX ), recently inked a global agreement with Chatham Therapeutics, LLC. Per the deal, Baxter will use Chatham's gene therapy know-how to develop and market new products for curing hemophilia B.

Baxter believes that investment in research and development (R&D) will further expand its BioScience segment's hemophilia product portfolio and be accretive to future sales. Bioscience sales were $1,462 million, up 4% (up 5% in constant currency) year over year, in the most recent quarter. The performance was attributable to higher demand for products utilized in the treatment of hemophilia and immune disorders, such as Advate and Gammagard Liquid (Immune Globulin Intravenous - Human), several specialty plasma-based therapeutics and vaccines.

Baxter wishes to run clinical trials on Chatham's unique Biological Nano Particles ("BNP"), a gene therapy technology, which has generated successful results during initial trials. The company paid $25 million for the program during its initial trials (which it will record as a special pre-tax in-process R&D expense in the second quarter of 2012) and plans to invest further, subject to certain terms and conditions.

The company has already been conducting several researches in hemophilia, including the BAX326 clinical trial for treating hemophilia B. It plans to file for an U.S. approval of BAX326 by late 2012.

Privately-owned Chatham Therapeutics, LLC is an associate of Asklepios BioPharmaceutical, Inc. ("AskBio"), which focuses on developing gene therapy based treatments for both hemophilia A and B.

The news regarding Baxter still remains mixed. On the positive side, Baxter's focus on life-sustaining products, which are not commoditized, partly insulates it from an economic downturn. The company is able to generate recurring revenues, and consistent cash flow, owing to its focus on chronic diseases. Among other positive factors, Baxter retains a strong product pipeline with several products in late-stage clinical development.

Baxter struck a deal, in December 2011, to buy Synovis Life Technologies, a well-known provider of mechanical and biological products for the repair of soft tissue utilized in a large number of surgical operations. The acquisition will further expand Baxter's offerings in the area of biosurgery and regenerative treatment.

Earlier, in November 2011, Baxter completed its acquisition of Baxa Corporation. The takeover highlights the company's continued commitment toward patient safety and nutrition. It also permits Baxter to provide a wider set of solutions for the safe preparation and delivery of IV medication. Baxa's know-how will benefit patients across the globe.

On the flip side, despite resilience in Plasma Proteins and Antibody Therapy sub-segments, we are concerned about stagnation in sales, a slightly somber outlook for hospital spending and tightening of reimbursement. We also account for the unfavorable impact of foreign exchange translation and possible dilution associated with the company's acquisitions of Baxa and Synovis.

Improved execution has lifted sentiment somewhat toward Baxter. It is a good bet for value investors willing to wait as fundamentals improve further. Among others, the company competes with Becton, Dickinson and Company ( BDX ) in certain niches. We currently have a Neutral long-term rating on Baxter. The stock currently retains a Zacks #3 Rank, which translates into a short-term "Hold" recommendation.

Follow this link:
Baxter Inks Deal with Chatham - Analyst Blog

By Eddie Wrenn

PUBLISHED: 11:26 EST, 5 June 2012 | UPDATED: 03:55 EST, 6 June 2012

Pain: All women have two 'X' chromosomes - potentially making them more prone to migranes

A female gene may be to blame for migraine - explaining why women are more likely to suffer from the debilitating headaches, research shows.

A study found a new region on the X chromosome as having a link to migraines, providing new evidence their might be a susceptibility gene involved.

All women have two X chromosomes while men have an X and a Y chromosome.

Researchers, led by Lyn Griffiths from Australias Griffith University, say more than one X chromosomal gene may be involved and believe a gene involved in iron regulation in the brain merits further attention.

Professor Griffiths based her study on genetic research of 300 inhabitants of remote Norfolk Isand, between Australia and New Zealand.

Many of the islanders are descended from survivors of the mutiny on the Bounty, moving there when they outgrown Pitcairn Island.

Eighty per cent of the inhabitants can trace their ancestry back to the mutiny.

Link:
'Female' gene to blame for migraines - which may explain why ladies are more prone than men

Editor's Choice Academic Journal Main Category: Genetics Also Included In: Pediatrics / Children's Health;Obesity / Weight Loss / Fitness Article Date: 05 Jun 2012 - 14:00 PDT

Current ratings for: 'Genetic Risk Scores And Obesity Later In Life Among Children'

The researchers explain that obesity can be inherited and GWASs (genome-wide association studies) have started to reveal the molecular roots of heritability by identifying SNPs (single-nucleotide polymorphisms) which are associated with higher BMIs (body mass indexes).

Daniel W. Belsky, Ph.D., and team wrote:

The researchers gathered data on 1,037 New Zealanders who were members of the Dunedin Multidisciplinary Health and Development Study. 52% of them were males. They were all born between April 1972 and March 1973. They were assessed every few years up to the age of 38 years.

Participants with higher GRSs (genetic risk scores) had greater BMIs between ages 3 to 38 for every age assessed. Children identified with a high genetic risk were found to have a 1.61 to 2.41 times higher chance of becoming obese during their teens to late thirties , and 1.90 times more likely to become chronically obese across over three assessments compared to the other kids.

Children at higher genetic risk experienced more severe adiposity rebound than other kids. Adiposity rebound means gaining fat after losing weight - piling the pounds back on. Adiposity rebound also appeared to occur earlier on among kids at higher genetic risk.

Children of normal weight at higher genetic risk, whose parents were overweight, were found to have faster growth and a greater chance of becoming obese.

The authors explained that genetic score risk contributed "independent and additive information" to predicting how much children might grow and/or become obese later on in life - this data went beyond family history data.

In the same journal, the authors concluded:

Go here to read the rest:
Genetic Risk Scores And Obesity Later In Life Among Children

While economies everywhere continue to face a global slowdown, investors should turn to the safety of stocks in a recession-proof sector, Jim Cramer said Tuesday on CNBC's "Mad Money." He cited Seattle Genetics as the perfect example of one such stock.

With a market capitalization of $2.4 billion, Seattle Genetics

The Bothell, Wash.-based firm champions the use of innovative biotechnology like engineered antibodies to target and kill cancer cells while sparing healthy cells. And though the stock isn't profitable just yet, it does have one drug Adcetris already on the market and is expected to start raking in material revenues in 2014.

Cramer also noted that at the American Society of Clinical Oncology conference, Seattle Genetics released "bullish phase two data" about the use of Adcetris to treat other types of lymphoma, in addition to the Hodgkin's and large cell strains of lymphoma the drug has already successfully treated.

To find out more about the company's prospects, Cramer sat down to chat with Clay Siegall, president and CEO of Seattle Genetics on Tuesday's show. Watch the video to see the full interview.

Call Cramer: 1-800-743-CNBC

Questions for Cramer?

Questions, comments, suggestions for the Mad Money website?

2012 CNBC.com

Read more:
Cramer Interviews Seattle Genetics CEO

Global medical products and services company, Baxter International, Inc. (BAX), recently inked a global agreement with Chatham Therapeutics, LLC. Per the deal, Baxter will use Chathams gene therapy know-how to develop and market new products for curing hemophilia B.

Baxter believes that investment in research and development (R&D) will further expand its BioScience segments hemophilia product portfolio and be accretive to future sales. Bioscience sales were $1,462 million, up 4% (up 5% in constant currency) year over year, in the most recent quarter. The performance was attributable to higher demand for products utilized in the treatment of hemophilia and immune disorders, such as Advate and Gammagard Liquid (Immune Globulin Intravenous Human), several specialty plasma-based therapeutics and vaccines.

Baxter wishes to run clinical trials on Chathams unique Biological Nano Particles (BNP), a gene therapy technology, which has generated successful results during initial trials. The company paid $25 million for the program during its initial trials (which it will record as a special pre-tax in-process R&D expense in the second quarter of 2012) and plans to invest further, subject to certain terms and conditions.

The company has already been conducting several researches in hemophilia, including the BAX326 clinical trial for treating hemophilia B. It plans to file for an U.S. approval of BAX326 by late 2012.

Privately-owned Chatham Therapeutics, LLC is an associate of Asklepios BioPharmaceutical, Inc. (AskBio), which focuses on developing gene therapy based treatments for both hemophilia A and B.

The news regarding Baxter still remains mixed. On the positive side, Baxters focus on life-sustaining products, which are not commoditized, partly insulates it from an economic downturn. The company is able to generate recurring revenues, and consistent cash flow, owing to its focus on chronic diseases. Among other positive factors, Baxter retains a strong product pipeline with several products in late-stage clinical development.

Baxter struck a deal, in December 2011, to buy Synovis Life Technologies, a well-known provider of mechanical and biological products for the repair of soft tissue utilized in a large number of surgical operations. The acquisition will further expand Baxters offerings in the area of biosurgery and regenerative treatment.

Earlier, in November 2011, Baxter completed its acquisition of Baxa Corporation. The takeover highlights the companys continued commitment toward patient safety and nutrition. It also permits Baxter to provide a wider set of solutions for the safe preparation and delivery of IV medication. Baxas know-how will benefit patients across the globe.

On the flip side, despite resilience in Plasma Proteins and Antibody Therapy sub-segments, we are concerned about stagnation in sales, a slightly somber outlook for hospital spending and tightening of reimbursement. We also account for the unfavorable impact of foreign exchange translation and possible dilution associated with the companys acquisitions of Baxa and Synovis.

Improved execution has lifted sentiment somewhat toward Baxter. It is a good bet for value investors willing to wait as fundamentals improve further. Among others, the company competes with Becton, Dickinson and Company (BDX) in certain niches. We currently have a Neutral long-term rating on Baxter. The stock currently retains a Zacks #3 Rank, which translates into a short-term Hold recommendation.

Read more from the original source:
Baxter Inks Deal with Chatham

Public release date: 4-Jun-2012 [ | E-mail | Share ]

Contact: David Eve celltransplantation@gmail.com Cell Transplantation Center of Excellence for Aging and Brain Repair

Tampa, Fla. (June 4, 2012) After carrying out a study comparing the repopulation efficiency of immature hepatic stem/progenitor cells and mature hepatocytes transplanted into liver-injured rats, a research team from Sapporo, Japan concluded that mature hepatocytes offered better repopulation efficiency than stem/progenitor cells.

Until day 14 post-transplantation, the growth of the stem/progenitor cells was faster than the mature hepatocytes, but after two weeks most of the stem/progenitor cells had died. However, the mature hepatocytes continued to survive and proliferate one year after their implantation.

The study is published in Cell Transplantation (21:1), now freely available on-line at http://www.ingentaconnect.com/content/cog/ct/.

"Cell-based therapies as an alternative to liver transplantation to treat liver disease have shown promise," said study corresponding author Dr. Toshihiro Mitaka of the Cancer Research Institute of the Sapporo Medical University School of Medicine, Sapporo, Japan. "However, the repopulation efficiency of two candidate cell sources - hepatic progenitor/stem cells and mature hepatocytes - had not been comprehensively assessed and questions concerning the efficiency of each needed to be resolved."

The researchers noted that the shortage of cell sources and the difficulties of cryopreservation have limited the clinical application of cell based therapies. Stem or progenitor cells have been considered candidate cells because they can expand in vitro and can be cryopreserved for a long time.

However, after transplantation into liver injured rats, the researchers found that stem/progenitor cells did not survive well and most of the transplanted cells had disappeared within two months. In contrast, the mature hepatocytes gradually repopulated the rat livers and continued doing so past one year.

The researchers noted that the sizes of the hepatocytes were not uniform.

"Unexpectedly, the small hepatocytes repopulated significantly less well than the larger ones," explained Dr. Mitaka. "We also found that serial transplantation did not enhance nor diminish the repopulation capacity of the cells to any significant degree."

Originally posted here:
Mature liver cells may be better than stem cells for liver cell transplantation therapy

06/04/2012

Gene Zimmerman, W3ZZ, of Gaithersburg, Maryland, passed away on Sunday, June 3. He was 71. Zimmerman wrote the popular QST column The World Above 50 MHz from 2002-2011. He also served on the ARRL Contest Advisory Committee, edited the VHF contesting column for CQ Contest magazine during its five-year lifespan and was director of the CQ VHF Contest from 2000-2002. An ARRL Life Member, Zimmerman earned VUCC on six bands: 50, 144, 222, 432, 903 and 1296 MHz, as well as DXCC, Worked All States and Worked All Continents on 6 meters. He was an early proponent of -- and participant in -- aggressive contest log checking.

First licensed in 1956 -- and an Amateur Extra since 1963 -- Zimmerman has logged several national Top-10 finishes in the ARRL November Sweepstakes (both modes), as well as a second-place North American finish in the CQ World Wide CW Contest (from VP2MDD). He also placed in the Top 10 several times in the ARRL VHF QSO Parties and in the ARRL VHF Sweepstakes.

Zimmerman earned a PhD in Microbiology from the University of Maryland in 1968. He began his professional career at the National Institutes of Health (NIH), where he spent a year as a technician in an NIH laboratory, studying respiratory viruses. This experience sparked an interest in virology and conquering the common cold. After this, he conducted early research at NIH, studying the relationship between retroviruses and cancer, the use of the simian model for studying leukemia and the use of interferon as an immune system modulator. In 1976, he joined the NIH Grants Associate Program, which groomed promising scientists for careers in managing NIH research programs. Zimmerman was then recruited to be the Scientific Review Administrator of the Allergy and Immunology Study Section of the Immunological Sciences Integrated Review Group, where he evaluated research proposals to provide funds for research in immunology.

Gene brought the same intensity and depth of knowledge of his career at the NIH to understanding propagation, said Ward Silver, N0AX. His tenure as the conductor of QSTs The World Above 50 MHz usually resulted in a sharp recounting and analysis of the months unusual on-the-air events. I learned something from every single column. But what most will remember about Gene, though, will be his amazing capacity for storytelling and the twinkling of his eyes as he told of the undoing of scoundrels with obvious and undiluted glee. Ive had the pleasure of being his roommate at Dayton and WRTC and I dont believe Ive ever laughed harder or longer. Gene knew where all the bodies were buried and relished his role as sage and historian.

Zimmerman was a shortwave listener before becoming a ham. After he got his ticket when he was a freshman at Yale University, Zimmerman became interested in weak signal VHF, due to his friendship with Paul Doane, W1HAD, who at the time was a college student at Brown. I remained active on the VHF bands until I left Connecticut in 1964, but I also developed an interest in HF and VHF contesting, he told the ARRL in June 2011. When I moved to Washington, DC, I became involved in HF contesting in a serious way, particularly building multi-op contest stations with Tom Peruzzi, W4BVV (SK). I returned to weak signal VHF in 1981 and built a pretty decent VHF station, which I have expanded to 10 GHz.

Unlike HF where some band is open for long distance communications all the time, Zimmerman said that openings on VHF are few and far between -- and extremely exciting when they happen. I guess I dont like things that are easy, so I chose to do VHF+, he explained. Over the years, I have worked more than 140 DXCC entities on 6 meters, 38 states and 9 DXCC terrestrially on 2 meters, 36 states on 222 MHz and VUCC on 50-1296 MHz. In contests, I have also been in the Top 10 nationally several times from my home station, and have won the multi-unlimited category four times with K8GP, the Delmarva VHF and Microwave Society. I think once you have built an interest in the VHF+ bands, it never goes away.

Gene was a pleasure to work with, witty and insightful, said QST Editor Steve Ford, WB8IMY. I am sure he will be greatly missed by many.

Amateur Radio has had its share of characters but none were more colorful or more widely respected than Dr Gene Zimmerman, W3ZZ -- a man who in one breath could identify the source of the worlds greatest hot dogs, explain once-in-a-lifetime propagation and recount the history of contesting and contesters, Silver said. We will all miss Genes presence greatly and it is a sad day for us all to learn of his passing.

Zimmerman was a member of the Delmarva VHF and Microwave Society, K8GP, the Grid Pirates Contest Group, a Past President of the Potomac Valley Radio Club and an honorary member of the Connecticut Wireless Association. Funeral arrangements are pending.

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Former “The World Above 50 MHz” Conductor Gene Zimmerman, W3ZZ (SK)

ScienceDaily (June 4, 2012) A University of Saskatchewan research team led by Tony Kusalik and Scott Napper have harnessed bioinformatics and molecular biology to create powerful software that promises to become a "must have" tool in drug development research labs the world over.

The software is used to analyze kinases -- a type of enzyme involved in virtually every cellular function, from energy use and reproduction to modifying gene expression. Licensing of the patented technology is currently underway, and a demonstration of its effectiveness recently appeared in the journal Science Signalling.

"This is a premiere example of what can be achieved through interdisciplinary and collaborative research," says Kusalik, a professor in the computer science department.

Kinases are often involved in cellular functions that go awry, such as when pathogens such viruses or bacteria "hijack" a cell's functions for their own purposes. Pathogens also have kinases of their own.

"Kinases have a central role in controlling cellular processes and are associated with many diseases. They're logical points for understanding biology and represent important treatment targets," says Napper, an associate professor of biochemistry with the U of S and senior scientist at the Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac).

The standard lab tool in kinase research is the microarray, which allows researchers to analyze many different kinases within a sample simultaneously. A microarray looks like a standard microscope slide with rows of spots, each spot representing a different molecular test.

"With older methods, it was like having a little flashlight in a cave -- you can see, but it doesn't tell you all that is there," Napper says. "These arrays give you the whole picture -- but you end up with absolutely mountains of data."

The problem for Napper and fellow VIDO-InterVac senior scientist Philip Griebel was that the mountains of data were making no sense. Griebel is also a faculty member with the U of S School of Public Health.

"They knew there were problems with the methodology they were following, because the results 'weren't working out,' but they didn't have sufficient expertise in bioinformatics to come up with an alternate method. That's where we came in," Kusalik says.

Kusalik is an expert in bioinformatics, which is the application of computers and information technology to biology and medicine. One well-known application of bioinformatics is DNA sequencing, including the Human Genome Project.

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Powerful new tool for research and drug development

CARLSBAD, Calif., June 5, 2012 /PRNewswire/ -- Life Technologies Corporation (NASDAQ: LIFE) today announced an expanded Ion AmpliSeq product line with the launch of new breakthrough Comprehensive Cancer and Inherited Disease Panels. These first of kind panels, when coupled with Ion AmpliSeq Designer V1.2, Ion AmpliSeq Library Kit 2.0 and the new Ion Reporter Software, represent complete solutions for scientists researching the genetic basis of human diseases.

Sequencing the millions of cancer research samples stored in bio-repositories around the world is a primary unmet need of the cancer research community. Analyzing these samples using next generation sequencing (NGS) has been difficult, as typically only nanogram amounts of DNA can be isolated, far less than current commercial protocols require. In addition, NGS creates a flood of data, requiring expensive bioinformatics expertise to interpret. The latest set of Ion AmpliSeq and Ion Reporter products from Ion Torrent offer turn-key solutions to overcome these challenges.

Bringing Simplicity and Speed to Disease Research Workflows

Ion AmpliSeq Panels, whether predesigned and therefore ready-to-use, or custom built to probe specific genes of interest, deliver a simplified, single day workflow comprising target selection, amplification, sequencing and analysis. Further, when using Ion Reporter Software, the integrated workflow also includes annotated readout detailing the biological significance of observed gene mutations. The breakthrough Ion AmpliSeq technology requires only tens of nanograms of input DNA, compared to technologies offered by other companies that require hundreds of nanograms or even micrograms of starting material.Orthogonal confirmation of variants observed with Ion AmpliSeq Panels is readily accomplished by selecting from 4.5 million ready-to-use TaqMan SNP Genotyping assays or by designing a custom TaqMan assay. TaqMan assays deliver "gold standard" sensitivity and specificity for SNP genotyping, and they may be analyzed in standard or digital PCR mode if increased sensitivity is required to detect low frequency or somatic mutations.

Scalability Demonstrated With Latest Edition of Ion AmpliSeq Designer Software

Initially launched in March, Ion AmpliSeq Designer has been immediately adopted by researchers world-wide, with over 1,000 custom designs submitted since inception. Ion AmpliSeq Designer Version 1.2 provides an additional leap in performance by generating up to 3,072 amplicons in a single tube allowing capture of up to 1 Mb of genetic sequence. This high level of multiplexing streamlines the workflow by ensuring that only 1 or 2 primer pools are needed for custom designs and also reduces the amount of input DNA required for analysis. Ion AmpliSeq Designer delivers exceptional performance, with target design rates and coverage uniformity up to 98%.

Improved Performance of Ion AmpliSeq Cancer Panel

In October of 2011 Ion Torrent launched the Ion AmpliSeq Cancer Panel, which has quickly become the product of choice for scientists working to advance clinical cancer research. Now, by pairing this 46 gene cancer hot spot panel with the new Ion AmpliSeq Library Kit 2.0, scientists can detect rare somatic mutations and enjoy 98% coverage uniformity and further reductions in strand bias.

New Ion AmpliSeq Comprehensive Cancer Panel

With input from leading cancer research institutions, the Ion AmpliSeq Comprehensive Cancer Panel (CCP) reveals tumor mutation profiles and is optimized for use with formalin fixed paraffin embedded, (FFPE) tissues. This panel allows sensitive, high coverage detection of rare genetic variants by employing more than 16,000 primer pairs targeting over 400 genes involved in tumor formation. Compared to whole exome sequencing, Ion AmpliSeq CCP requires only 40 ng of input DNA, has a significantly lower price, and provides nearly 10-fold better coverage of individual genes, providing better sensitivity and specificity to detect somatic mutations.The Ion AmpliSeq Comprehensive Cancer Panel delivers exceptional quality, with coverage uniformity and on target bases both greater than 90%.

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New Breakthrough Ion AmpliSeq™ Technology Delivers the Most Rapid and Comprehensive Sequencing of Gene Mutations to ...

ScienceDaily (June 4, 2012) New hope has arrived for migraine sufferers following a Griffith University study with the people of Norfolk Island.

Led by Professor Lyn Griffiths from the University's Griffith Health Institute, the team has identified a new region on the X chromosome as playing a role in migraine.

The research provides compelling evidence for a new migraine susceptibility gene involved in migraine. The study also indicated that there may be more than one X chromosomal gene involved and implicated a gene involved in iron regulation in the brain.

All females have two X chromosomes whilst males have an X and a Y chromosome.

"These results provide more support for the role of the X chromosome in migraine and may explain why so many more females suffer from the disorder," said Professor Griffiths.

Tracking down and identifying the various genes that cause migraine is very important as it provides insights to allow us to develop better means of diagnosis and more targeted treatments.

"Currently, 12 per cent of the population suffers from migraine. Even though we have some very good treatments for this very debilitating disease, they certainly don't work for everyone and can have some adverse side effects. Hence there is a real need to develop new migraine treatments."

This National Health and Medical Research Council funded work involved a unique population study of the remote Norfolk Island where 80 per cent of inhabitants are able to trace their ancestry back to the famous historical event, The Mutiny on the Bounty.

"This population was used due to its unusual pedigree structure in which genetic relationships can be traced through genealogical data to the island's original founders, and also the high incidence of migraine sufferers in this population. It's very useful for gene mapping purposes because of the reduced genetic and environmental diversity," said Professor Griffiths.

A comprehensive chromosome analysis of around 300 Norfolk participants from a large multigenerational Norfolk family, including many who are affected by migraine, was conducted using DNA samples obtained from the islanders.

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New hope for migraine sufferers: Female gene link identified

CARLSBAD, Calif.--(BUSINESS WIRE)--

Percepta Associates is pleased to announce the launch of the 2012 Gene Expression Profiling, Series 4 Life Science Dashboard market research report, providing rapid access to actionable key market indicators for the gene expression profiling market. The 2012 Dashboard draws comparisons to market data reported in Percepta's 2008 and 2010 Gene Expression Profiling Dashboards, including market size, competitive shares, growth rates, customer satisfaction/propensity to switch, and end-user practices, in an 'at a glance' easy to understand format, allowing suppliers of products for gene expression profiling to easily track the effectiveness of marketing strategies and tactics over time. Market segments analyzed, including several new areas of focus, are as follows:

Life Technologies (LIFE) is the leading supplier in five of the nine segments analyzed, with one entrenched leadership position. Affymetrix (AFFX) and Illumina (ILMN) hold dominant positions in two of the segments not led by Life Technologies. Bio-Rad (BIO) was also cited among the leading suppliers in several segments. Furthermore, findings reveal that over half of respondents, in six of the nine segments expressed an interest in switching primary suppliers. Several gene expression profiling market segments continue to experience rapid growth, with annual rates exceeding 10% in two key segments. Even as next-generation sequencing methods rapidly enter the mainstream, our data shows that expression profiling methods will continue to be necessary tools in the advancement of life science research, said Alison Rowland, Principalat Percepta.

The 2012 Gene Expression Profiling, Series 4 Life Science Dashboard also analyzes current primary and secondary applications for each market segment, uncovering key downstream application changes observed over the past four years. Specific product and protocol improvement needs that may drive customer switching behavior are cited by respondents and revealed as verbatim comments in this report.

The 2012 Gene Expression Profiling Dashboard was developed from responses to a 23-question survey completed by 460 scientists predominantly located in North America and Europe. These respondents perform gene expression profiling methods on a regular basis.

To view Gene Expression Profiling Dashboard Series 4 sample data and the survey questionnaire visit:

http://www.perceptaassociates.com/publications/12_gene_expression_overview.shtml

About Percepta

Founded in 2005 in Carlsbad, California Percepta Associates is a specialized consultancy providing expert market research, strategic business planning, portfolio management, product and corporate branding and marketing communications services to life science research suppliers globally. For more information visit: http://www.perceptaassociates.com or call 760 431 6300.

For more information visit http://www.perceptaassociates.com.

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Affymetrix, Illumina and Life Technologies Hold Entrenched Leadership Positions in Key Gene Expression Profiling ...

Public release date: 4-Jun-2012 [ | E-mail | Share ]

Contact: Mary Jane Gore mary.gore@duke.edu 919-660-1309 JAMA and Archives Journals

CHICAGO A 38-year longitudinal study of New Zealanders suggests that individuals with higher genetic risk scores were more likely to be chronically obese in adulthood, according to a report published in the June issue of Archives of Pediatrics & Adolescent Medicine, a JAMA Network publication.

Obesity is capable of being inherited and genome-wide association studies (GWASs) have started to uncover the molecular roots of heritability by identifying multiple single-nucleotide polymorphisms (SNPs) associated with higher adult body mass index (BMI), the authors write in their study background.

"In this study, we asked how SNPs with replicated GWAS evidence for association with adult BMI relate to growth across the first four decades of life and to adult obesity in a birth cohort followed up prospectively from birth through 38 years of age," Daniel W. Belsky, Ph.D., of Duke University, Durham, N.C., and colleagues write in the study background.

Study participants were members of the Dunedin Multidisciplinary Health and Development Study, an investigation of health and behavior in a complete birth cohort. The 1,037 study members (52 percent were male) were born between April 1972 and March 1973 in Dunedin, New Zealand. Assessments were performed every few years starting at birth until 38 years.

Children with higher genetic risk scores (GRSs) had higher BMIs at every age assessed from age 3 through 38 years. Children at high genetic risk were 1.61 to 2.41 times more likely to be obese in their second, third and fourth decades of life and were 1.90 times more likely to be chronically obese across more than three assessments compared with children at low genetic risk, according to study results.

Adiposity rebound, when children begin to gain body fat after losing it during early childhood, occurred earlier in development and at higher BMI for children at higher genetic risk, the results indicate.

Higher genetic risk also predicted faster growth and increased obesity risk in children with normal-weight and overweight parents, the study results note. The authors comment that the GRS contributed "independent and additive information" to the prediction of children's growth and their risk for obesity in adulthood beyond the family history information.

"Thus, the results present compelling evidence that SNPs identified in GWASs of adult BMI and other obesity-related phenotypes predispose to more rapid growth in childhood, leading to increased risk for obesity in adulthood, and provide information not forthcoming from a simple analysis of family history," the authors conclude.

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Genetics, rapid childhood growth and the development of obesity

SAN DIEGO--(BUSINESS WIRE)--

Pathway Genomics Corporation, a clinical genetic testing laboratory and results interpretation service based in San Diego, has been selected by San Diego Venture Group as one of 30 cool companies to be featured at its 10th Annual Venture Summit on June 6. Selected from a field of over 150 applicants, Pathway Genomics and the other 29 companies will be a prominent part of the event, which draws more than 100 venture capitalists and 500 attendees.

The selection is a reminder that companies like Pathway are at the forefront of a major shift in the way medicine is practiced throughout the world, said Jim Plante, Pathways founder and CEO.

Pathway provides genetic tests for drug responses, nutrition and exercise response, inherited genetic conditions, and risk of many diseases. Pathway consists of more than 40 scientific and medical professionals, including medical doctors, molecular geneticists, and genetic counselors, as well as a world-leading scientific advisory board.

To learn more about Pathways genetic testing services, visit http://www.pathway.com. For more information about San Diego Venture Groups Cool Companies 2012 and its 10th Annual Venture Summit, visit http://www.sdvg.org/venturesummit.

About Pathway Genomics

Pathway Genomics owns and operates an on-site genetic testing laboratory that is accredited by the College of American Pathologists (CAP), accredited in accordance with the U.S. Health and Human Services Clinical Laboratory Improvement Amendments (CLIA) of 1988, and licensed by the state of California. Using only a saliva sample, the company incorporates customized and scientifically validated technologies to generate personalized reports, which address a variety of medical issues, including an individuals carrier status for recessive genetic conditions, food metabolism and exercise response, prescription drug response, and propensity to develop certain diseases such as heart disease, type 2 diabetes and cancer. For more information about Pathway Genomics, visit http://www.pathway.com.

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Pathway Genomics Selected as a “Cool Company” by San Diego Venture Group

First Bedside Genetic Test Could Prevent Heart Complications

A genotyping test from a Canadian biotech company enables timely personalized drug treatment.

For some cardiac patients, recovery from a common heart procedure can be complicated by a single gene responsible for drug processing. The risk could be lowered with the first bedside genetic test of its kind. The test shows promise for quickly and easily identifying patients who need a different medication.

Quick test: This shoebox-sized device from Spartan Bioscience supports the first bedside genetic test. Spartan Bioscience

After a patient receives a heart stenta small scaffold that props open an arteryhis or her doctor will prescribe a blood thinner to prevent platelets from building up inside the device. However, for some 70 percent of patients with Asian ancestry and 30 percent of patients with African or European ancestry, a single genetic variant will prevent one of the most commonly prescribed blood thinners from working. Alternatives exist, but they are more expensive, so hospitals could use an easy way to identify who does and does not need the more expensive drug.

Canada's Spartan Biosciencehas developed a near "plug-and-play" genotyping device that allows nurses and others to quickly screen patients at the bedside, perhaps while they are undergoing the stent placement procedure. Users take a DNA sample from a patient's cheek with a specialized swab, add the sample to a disposable tube, and then place the tube and sample in a proprietary shoebox-sized machine and hit a button. Shortly thereafter, the user receives a printout of the patient's genetic status for the drug-processing variant. The whole procedure takes about an hour. Most clinicians currently have to wait several days for similar information to come from off-site genetics testing companies.

"For six years we've been plugging away at this, and we finally broke through about a year and a half ago," says Spartan Bioscience founder Paul Lem. He says the simple test came to life with innovations at every stepfrom the special swab that collects the right amount of DNA, to the chemicals in the disposable reaction tube, to the software that automates the DNA readingand a team with diverse backgrounds including his in medicine and molecular biology and others' in optical hardware.

Lem has kept an eye on other companies trying to create a bedside genetic test, some going after the same variant, and calculates that over $1 billion in capital has been spent over the last five years in this area.

The University of Ottawa Heart Institute researchers conducted a proof-of-principle trial for the device and found that the bedside test is effective at quickly identifying carriers of the drug-processing variant and can be performed by nurses with minimal training. The findings were published in The Lancet last week.

"The stakes are pretty high" for the risks associated with the variant in the test, says Euan Ashley, a cardiologist with Stanford's Center for Inherited Cardiovascular Disease. Patients who receive a stent implant after a heart attack or as a preventive measure are at risk for serious adverse events if their bodies cannot process a commonly prescribed anti-platelet drug into its active form. "There's a startling number of people who carry the variant, which leaves them at risk," says Ashley. "Being able to get an answer within an hour or twowhen you are thinking of a patient's heartis a pretty compelling case for [testing for it]."

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First Bedside Genetic Test Could Prevent Heart Complications

AMES, Iowa, June 4, 2012 (GLOBE NEWSWIRE) -- NewLink Genetics Corporation (Nasdaq:NLNK - News) today announced that data from Phase 1 and Phase 1B studies evaluating NLG8189 (D-1MT, 1-methyl-D-tryptophan or d-1-Methyltryptophan) will be presented in an oral presentation at the American Society of Clinical Oncology (ASCO) 2012 Annual Meeting being held in Chicago, IL in the E Arie Crown Theater from 3:15 to 3:30PM. The data show that NLG8189 is safe and well tolerated, with a favorable pharmacokinetic profile demonstrating good oral bioavailability. In addition, NLG8189 reached targeted therapeutic levels in the absence of serious toxicity. Interestingly, symptoms of hypophysitis (inflammation of pituitary) were observed in some patients suggesting early signs of biological activity. Furthermore, NLG8189 demonstrated a favorable safety profile in combination with Taxotere, as well as in combination with adenoviral autologous dendritic cell (DC) vaccines, with promising early signs of activity. These studies were conducted in conjunction with the National Cancer Institute (NCI).

Dr. Hatem Soliman, author of the abstract entitled "A phase I study of 1-methyl-d-tryptophan in combination with docetaxel in metastatic solid tumors" and also presenter of an oral abstract, commented, "In light of this favorable safety profile of NLG8189 and signs of activity we are especially interested in expanding our understanding of the mechanism underlying this compound's effect on the key immunomodulatory IDO pathway. The high response rate to chemotherapy after treatment with vaccine and NLG8189 suggests chemosensitization is occurring. In particular, we observed that 75% (6 out of 8 patients) responded to a combination of carboplatin and gemcitabine follow-on regimen including one complete response in a fifth line therapy."

Phase 1 and Phase 1B Study Designs

NewLink/NCI have completed Phase 1 single-agent pharmacokinetic/safety studies of the drug. Currently, two Phase 1B/2 clinical trials are enrolling patients to evaluate NLG8189 in combination with other cancer therapies. The initial Phase 1 dose escalation study evaluated 48 patients in escalating doses from 200 mg to 2,000 mg BID. The first Phase 1B clinical trial has primary endpoints assessing safety and efficacy of NLG8189 in combination with an Ad-p53 autologous dendritic cell vaccine for solid malignancies with p53 mutations, such as lung, breast and colon cancers. The second Phase 1B clinical trial has primary endpoints assessing safety and efficacy of escalating doses of NLG8189 in combination with Taxotere for patients with advanced stage solid tumors for which Taxotere is the standard-of-care, such as metastatic breast, prostate, ovarian and lung cancers. Furthermore, in breast cancer patients who had already received multiple prior chemotherapy regimens before treatment with DC vaccine and NLG8189, a 50% objective response rate was found when patients were next administered further salvage chemotherapy. This response rate was unexpected in patients who were so heavily pretreated and suggests that a chemosensitization effect occurred.

Study Findings

Initial Phase 1 studies confirmed that the drug has early signs of activity, good oral bioavailability, a favorable half-life that allows drug accumulation to levels estimated to be within the therapeutic range and that it is tolerated very well by patients. The adverse events were generally mild and self-limited, including several cases of measurable but easily managed hypophysitis that developed in immunologically sensitized patients, an indication that NLG8189 can elevate immune activation above baseline to clinically detectable levels. In the Phase 1B study of Taxotere plus NLG8189, patients with advanced solid tumors were shown to tolerate the drug combination at the maximum dose and are now being treated with this new drug combination and followed for efficacy. Similarly, the study combining Ad-p53 vaccine/NLG8189 has reached its maximum dose without limiting toxicity and is now collecting efficacy data.

"We have been encouraged by the data from the Phase 1 studies as we see very favorable safety and pharmacokinetic profiles for this drug," said Dr. Nicholas Vahanian, President and Chief Medical Officer of NewLink Genetics. He added "The evidence of biologic activity is encouraging, especially given that the immune-related events observed in several patients are a side effect that has correlated with positive clinical outcomes in studies of other immune-modulatory agents such as ipilimumab. It has always been our strategy to develop NLG8189 as a component of combination treatment with other anti-cancer agents and to explore how the potential chemosensitization observed in these studies might be further exploited."

About NLG8189

NLG8189 is a small-molecule, orally bioavailable product candidate based on NewLink's proprietary IDO pathway inhibitor technology. Preclinical experiments have demonstrated a strong, synergistic anti-tumor effect without increased toxicity when NLG8189 was administered in combination with a number of currently available chemotherapeutic agents. IDO pathway inhibitors, including NLG8189, represent a potential breakthrough approach to cancer therapy using small-molecule, anti-toleragenic product candidates intended to combat the mechanisms by which tumors evade immune-mediated destruction. IDO is an enzyme that regulates immune response by suppressing T-cell function and creating local tumor immune escape. Recent studies have demonstrated that IDO is overexpressed in many cancers, within both tumor cells as a direct defense against T-cell attack, and also within antigen presenting cells in tumor draining lymph nodes whereby IDO promotes peripheral tolerance to tumor-associated antigens ("TAAs"). When hijacked by developing cancers in this manner, IDO may facilitate the survival, growth, invasion, and metastasis of malignant cells expressing TAAs that might otherwise be recognized and attacked by the immune system as foreign.

About NewLink Genetics Corporation

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Data From Phase 1 and Phase 1B Studies of NewLink Genetics' IDO Pathway Inhibitor (NLG8189) Presented at 2012 ASCO ...

SANTA MONICA, Calif. & BOTHELL, Wash.--(BUSINESS WIRE)--

Agensys, Inc., an affiliate of Tokyo-based Astellas Pharma Inc., and Seattle Genetics, Inc. (SGEN) today announced interim data from a phase I clinical trial evaluating ASG-5ME for the treatment of castration-resistant prostate cancer (CRPC). ASG-5ME is an antibody-drug conjugate (ADC) targeting the SLC44A4 antigen that is being co-developed by both companies for the treatment of solid tumors. The data are being presented at the American Society of Clinical Oncology (ASCO) annual meeting being held June 1-5, 2012 in Chicago, IL.

SLC44A4 is an attractive target in prostate cancer and is present in the majority of patients with both localized and metastatic disease, said Leonard Reyno, M.D., Senior Vice President and Chief Medical Officer of Agensys. The current Phase I data demonstrates the tolerability of this antibody drug conjugate and further evaluation of safety and antitumor activity in patients with castration resistant prostate cancer is ongoing.

It is encouraging to observe these preliminary data with ASG-5ME in prostate cancer, a disease for which late-stage patients need additional therapeutic options, said Jonathan Drachman, M.D., Senior Vice President, Research and Translational Medicine of Seattle Genetics. In addition to prostate cancer, our two companies are continuing to evaluate the potential use of ASG-5ME in other solid tumor indications. In parallel, we are collaborating with Agensys to co-develop ASG-22ME, an ADC targeting Nectin-4 for solid tumors.

Phase 1 trial of ASG-5ME in metastatic castration-resistant prostate cancer (CRPC) (Abstract #4568) ASG-5ME is being evaluated in a single-agent phase I clinical trial to determine the maximum tolerated dose (MTD) and to assess the safety, pharmacokinetic profile and antitumor activity of escalating doses of ASG-5ME. At the time of data analysis, 26 patients were enrolled. The median age of the patients was 69.5 years and the median baseline prostate-specific antigen (PSA) level was 82.25.

Key findings, presented by Dr. Michael Morris from Memorial Sloan Kettering Cancer Center in New York, NY, and clinical investigator on the study include:

The phase I trial is ongoing, with enrollment to two expansion cohorts in chemotherapy nave and chemotherapy exposed CRPC patients planned.

Seattle Genetics and Agensys recently completed enrollment in a phase I pancreatic cancer trial of ASG-5ME dosed weekly. The companies plan to evaluate ASG-5ME in patients with gastric cancer based on preclinical expression data.

About ASG-5ME ASG-5ME is an ADC composed of a fully human antibody directed to SLC44A4, a solute carrier antigen family member identified by Agensys to be overexpressed in epithelial cancers, including more than 80 percent of samples derived from patients with prostate, pancreatic and gastric cancers. The antibody is attached to monomethyl auristatin E (MMAE) via an enzyme-cleavable linker using Seattle Genetics proprietary technology. The ADC is designed to be stable in the bloodstream, but to release MMAE upon internalization into SLC44A4-expressing tumor cells, resulting in targeted cell-killing.

Seattle Genetics and Agensys are co-developing and will globally co-commercialize and share profits on a 50:50 basis for ASG-5ME and ASG-22ME. Seattle Genetics also has an option for 50:50 cost and profit-sharing of a third ADC program at the time of investigational new drug submission.

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Agensys and Seattle Genetics Announce Interim Phase I Data from ASG-5ME Clinical Trial for Prostate Cancer

AMES, Iowa, June 4, 2012 (GLOBE NEWSWIRE) -- NewLink Genetics Corporation (Nasdaq:NLNK - News) announces that its HyperAcute(R) Pancreas (algenpantucel-L) Immunotherapy will be featured today in a poster presentation (abstract number 4049) at the American Society of Clinical Oncology (ASCO) 2012 Annual Meeting being held in Chicago, IL. The abstract entitled "Addition of algenpantucel-L immunotherapy to standard of care (SOC) adjuvant therapy for pancreatic cancer" will be shown in S Hall A2 from 8:00AM to 12:00PM . The study results show 37%, 59% and 121% improvement in 1-, 2- and 3-year survival, respectively, as compared to standard-of-care.

Dr. Jeffrey M. Hardacre, the study's Principal Investigator, from the University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, OH stated, "As a surgeon who regularly treats patients suffering from pancreatic cancer, and being accustomed to the dismal prognosis for these patients, I am highly encouraged with the exceptional overall survival data from this study."

"Given that the primary endpoint in our pivotal Phase 3 study targeting similar patients is overall survival, this data supports our cautious optimism," said Dr. Nicholas Vahanian, President and Chief Medical Officer of NewLink Genetics.

Key data from the 69 patient Phase 2 algenpantucel-L trial demonstrated:

The primary endpoint of the study, 12-month disease free survival (DFS), was 62%. The median DFS was 14.1 months. Subgroup analysis showed that patients receiving 300 million cells/dose had a 12-month DFS of 81%, while those receiving 100 million cells/dose had a 12-month DFS of 51% (p=0.02, Fisher's Exact). Prognostic criteria did not significantly differ between the two groups.

Overall 12-month survival was 86%. The predicted 12 month overall survival in our study was 63%. Subgroup analysis showed that patients receiving 300 million cells/dose had an overall 12-month survival of 96%, while those receiving 100 million cells/dose had an overall 12-month survival of 79% (p=0.053, Fisher's Exact). Two-year overall survival in our study was 51% with a predicted survival of 32% and 3-year overall survival was 42% with a predicted survival of 19%. Predicted survivals were computed using prognostic factors gathered for each patient and calculated using a nomogram published by Brennan et al from Memorial Sloan Kettering Cancer Center. Over the 33 month median follow up period of the study, the percentage improvement in overall survival rate compared to nomogram analysis increased over time. These data are consistent with recent studies of active immunotherapies (Sipuleucel-T and Ipilimumab) in that immune benefits appear greater in some patients over time.

Prominent eosinophil responses have been observed with the majority of patients demonstrating measurable increases in peripheral blood eosinophilia. In addition to eosinophilic infiltrates at the injection site in all tested patients, 70% developed eosinophilia, with 30% showing persistent eosinophilia for up to 2 years.

The HyperAcute(R) Pancreas immunotherapy product candidate, also referred to as algenpantucel-L, demonstrated good tolerability and a favorable safety profile with no grade four adverse events considered attributable to the immunotherapy. The predominant adverse events related to the immunotherapy were grade one or two injection site reactions, all treated with conservative local therapies.

Anecdotally, three patients with cancer recurrence after receiving algenpantucel-L obtained complete radiographic responses with the use of subsequent chemotherapy. As of May 16, 2012, all three patients remain in remission with no evidence of disease for periods ranging from six to 36 months. "We are presenting data from three different HyperAcute products at ASCO this year and each of these has generated intriguing data that provide insights into the activity and mechanisms associated with the treatment of patients with HyperAcute immunotherapies," stated Dr. Charles Link, CEO and Chief Scientific Officer of NewLink Genetics. "These observations include survival advantages that improve over time, objective responses, novel immunological findings and chemosensitization."

About the Phase 2 Study

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NewLink Genetics Reports Two- and Three-Year Overall Survival Data From Its Phase-2 HyperAcute(R) Pancreas ...

AMES, Iowa, June 4, 2012 (GLOBE NEWSWIRE) -- NewLink Genetics Corporation (Nasdaq:NLNK - News) announced its HyperAcute(R) Lung (tergenpantucel-L) immunotherapy will be featured today in a poster presentation (abstract number 2571) at the American Society of Clinical Oncology (ASCO) 2012 Annual Meeting being held in Chicago, IL. The abstract entitled "Correlation of interferon-g (IFN) response with survival in a phase II hyperacute (HAL) immunotherapy trial for non-small cell lung cancer (NSCLC)" will be shown in S Hall A2 from 8:00AM to 12:00 PM. The study presented by Dr. John C. Morris, Professor and Director of Thoracic Cancer Division at the University of Cincinnati, demonstrated a direct correlation between immune response and survival in non-small cell lung cancer patients. In addition, patient survival compared favorably to that seen in patients receiving other second-line chemotherapy agents, suggesting encouraging clinical benefit.

"The overall survival data is particularly remarkable when compared to current standard-of-care, which primarily utilizes cytotoxic chemotherapy agents with their associated debilitating side effects," commented Dr. Nick Vahanian, President, Chief Medical Officer, NewLink Genetics.

"These data suggest an intriguing relationship between a patient's immunological response to tergenpumatucel-L and overall survival," said Dr. John C. Morris. He added, "Survival of the late stage patients in this study compares favorably with that seen in approved agents and there is emerging data to suggest that patient response to some of these agents may be enhanced by prior treatment with tergenpumatucel-L."

Phase 1B/2 Study Design

Seventeen patients were treated in the Phase 1 portion of the study and 37 patients were treated in the phase 2 portion. Patients had metastatic or recurrent NSCLC and had failed first-line chemotherapy. Twenty-eight of the 37 phase 2 patients were evaluable for clinical response. All phase 2 patients received 300 million cells per injection every two weeks for up to eight scheduled doses. Serum samples were collected before and after immunization and then at two-month follow-up visits. Peripheral blood mononuclear cells (PBMC) were collected prior to immunization and after the fourth and eighth vaccinations. Response was determined using RECIST criteria.

Results

There were 28 patients in the phase 2 portion of the study evaluable for response. Among these patients median overall survival was 11.3 months. Eight patients (28.5 percent) demonstrated stable disease after 16 weeks of treatment, including one patient that initially progressed and later regressed, surviving over 40 months. Eighteen patients with pre-immunization and post-immunization serum samples were tested for elevations in interferon-gamma response to drug. Eleven of these 18 responded with increased interferon-gamma, and the overall survival of these patients was 21.9 months. The increase in overall survival of patients with increased interferon gamma compared to non-responders was statistically significant with a p-value of 0.044. Six of the 11 responders showed reactivity to CL4-H522, a cellular target not present in HyperAcute Lung, suggesting cross priming to shared antigens.

Safety and Tolerability

No serious adverse events were reported as definitely or probably attributable to HyperAcute Lung. The most frequently observed adverse events attributable to the therapy were skin reactions at the site of injection. These were generally either acute inflammatory reactions or delayed-type hypersensitivity reactions that resolved without intervention in the vast majority of cases.

Dr. Charles Link, CEO and Chairman of NewLink, stated that, "We are gratified that in addition to seeing positive clinical data with our HyperAcute-Lung product candidate, this study provides us with meaningful insight into the fundamental mechanisms by which this class of immunotherapies work."

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NewLink Genetics HyperAcute(R) Lung (tergenpumatucel-L) Immunotherapy Demonstrates a Correlation Between Immune ...