Aestus and Eisai Ally to Develop Treatments for Psychiatric Disorders

Aestus Therapeutics and Eisai have agreed to work together on the R&D of therapeutics for psychiatric disorders. The multiyear collaboration will entail preclinical validation of Aestus’ compounds leading to clinical proof-of-concept studies.

Aestus’ candidates were identified through its proprietary analysis of gene-expression datasets, coupled with biological pathway mining on data from relevant disease models. Along with Eisai, the firm will work toward picking lead candidates for further development.

Aestus reports that it has several products for neuropathic pain that are ready to enter Phase II studies. On June 28, Aestus licensed Astellas Pharma’s FK614, a PPAR-gamma agonist, to develop the product for postherpetic neuralgia. The first clinical trial is expected to start later this year. On June 9, the company was awarded a $2 million SBIR grant from the NIH to advance its pain candidates.

Beyond neuropathic pain, the Aestus technology is currently being applied to ALS and schizophrenia. On March 17, the ALS Therapy Development Institute and Aestus reported plans to test potential small molecule compounds to slow or stop the progression of ALS.

Pfizer to Study Liver Cancer in Korean Patients with Samsung Medical Center

Pfizer formed a research partnership with Samsung Medical Center to generate gene-expression profiles of tumors from Koreans with liver cancer. The hope is that the findings will lead to targeted therapeutics that can be used not just in Korea but also in the rest of Asia.

A research team led by Samsung Medical Center scientists including Prof. Park Cheol-Guen, Prof. Im Ho-Young, and Prof. Paik Soon-Myung, director of the cancer research center, will conduct research in Seoul. Neil Gibson, Ph.D., vp of oncology research, will be responsible for the joint research program at Pfizer.

Samsung Medical Center has built a base of specimens in the liver cancer area. “This partnership will serve as a great opportunity to combine Pfizer's know-how in drug development and Samsung Medical Center's extensive genome information and technology in the liver cancer area,” says Dr. Gibson. “We further plan to share the ownership of collected and analyzed data with Samsung Medical Center.”

Pfizer signed a memorandum of understanding with the Ministry of Health and Welfare in 2007, agreeing to invest $300 million in R&D in Korea. As part of its commitment, the company also formed a strategic partnership with the Korea Research Institute of Bioscience and Biotechnology and has been leading joint research since then.

In February Pfizer linked up with Eli Lilly and Merck & Co. to set up the Asian Cancer Research Group (ACRG) to concentrate on drug R&D for the most common cancers in Asia. The nonprofit company will initially focus on lung and gastric cancers, which are two of the most common cancers in Asia.

The aim for ACRG is to generate a pharmacogenomic cancer database comprising data from about 2,000 lung and gastric cancer tissue samples. The resulting data will be made publicly available to researchers and expanded through the addition of clinical data from a longitudinal analysis of patients.

The ACRG will initially establish collaborative relationships throughout the Asian region to collect tissue samples and data. “The ACRG is about sharing information for the common good,” stresses Kerry Blanchard, M.D., Ph.D., vp and leader of drug development in China for Lilly.

Pfizer and SMC Collaborate on Liver Cancer

Source:PRNewswire

NEW YORKJuly 14 /PRNewswire-FirstCall/ — Samsung Medical Center and the world's leading bio-pharmaceutical company Pfizer Inc. (NYSE: PFE) announced that they have formed a research partnership to jointly analyze tumors from Korean patients to generate gene expression profiles and that may ultimately direct therapies and enhance clinical outcomes in the patients with liver cancer.

(Logo: http://photos.prnewswire.com/prnh/20100416/PFIZERLOGO )

(Logo: http://www.newscom.com/cgi-bin/prnh/20100416/PFIZERLOGO )

The two organizations held a signing ceremony at the main conference hall located on the fifth floor of Samsung Medical Center in Seoul on June 14 to commemorate the initiation of the collaboration.  A research team led by top scientists at Samsung Medical Center, including Prof.Park Cheol-Guen, Prof. Im Ho-Young and Prof. Paik Soon-Myung, Director of the Cancer Research Center, will conduct research in Seoul, while Dr. Neil Gibson, Vice President of Oncology Research, will be responsible for the joint research program at Pfizer.

Pfizer expanded into the market for targeted anticancer agents with the launch of Sutent, an anticancer agent used to treat an advanced form of kidney cancer.  Since then, the company has been consistently investing in research and development of innovative drug candidates and potential treatments for patients with liver cancer, a type of cancer especially prevalent in Asia, to address the growing need for an anticancer drug treating liver cancer in the Asian market in the future.  Seeing the world-class clinical environment and outstanding research capabilities in Korea, the global pharmaceutical company formed a research partnership with Samsung Medical Center as part of its commitment.

Samsung Medical Center has been laying the solid foundation for development of new anticancer drugs, providing top-quality medical service through organic collaboration with other organizations; building an extensive base of specimens in the liver cancer area; and accumulating the know-how for diagnosis and treatment of liver cancer.  Samsung Medical Center was named to join the "Group of Leading Research-based Hospitals," a large-scale national project led by the Ministry of Health and Welfare in 2009, to work with leading local and global pharmaceutical companies for an open research project designed to develop novel bio drugs that will help the country to cure intractable diseases.

"We are pleased to have an opportunity to work with the world's No. 1 pharmaceutical company Pfizer to better understand cancer in Korean patients, with the goal of being able to send a new message of hope for patients with liver cancer across the world (especially in Asia)," said Choi Han-Yong, president of Samsung Medical Center.

"This partnership will serve as a great opportunity to combine Pfizer's know-how in drug development and Samsung Medical Center's extensive genome information and technology in the liver cancer area," said Neil Gibson, vice president of Oncology Research Unit in Pfizer Inc.  "We further plan to share the ownership of collected and analyzed data with Samsung Medical Center, contributing to advance of a variety of oncology research in Korea."  Pfizer signed a memorandum of understanding with the Ministry of Health and Welfare in 2007, agreeing to invest 300 million dollars in R&D in Korea.  As part of its commitment, the company also formed a strategic partnership with the Korea Research Institute of Bioscience and Biotechnology and has been leading joint research since then.

Cavity Fighting Bacteria

We've all been taught that the way to prevent cavities is to brush, floss, and visit the dentist regularly. Researchers at the University of Florida have taken a different approach to fighting tooth decay. They have altered the bacterium Streptococcus mutans, which is known to cause tooth decay, so that it is no longer harmful to teeth.

The leading researcher in the study, dentist J. D. Hillman, accomplished this task by stripping the bacterium of its ability to produce lactic acid. It is this byproduct of the breakdown of sugar by Streptococcus mutans that causes tooth decay. If the bacteria are not able to produce lactic acid tooth decay is stopped.

As many as 500 different species of bacteria inhabit your mouth and can colonize on your teeth and gums. When you eat a meal bacteria help to digest the food and sugar left on your teeth and gums. In the process lactic acid is produced which breaks down tooth enamel and leads to cavitiesStreptococcus mutans has been found to be the most cariogenic (promotes tooth decay) of these bacteria.


Streptococcus mutans. Image courtesy of Fusa
o Ota, University of Tokushima, Japan.
 

The genetically altered strain of Streptococcus mutans appeared to thrive on sugar. It was tested on rats with positive results. Researchers introduced a solution containing the bacterial strain into the oral cavity of rats. The rats were fed a high sugar diet and showed no evidence of tooth decay. Researchers found that the strain was able to stay on the surface of the teeth indefinitely and prevented the natural strain from colonizing on the teeth. The altered strain is genetically stable and no ill effects have been noted.

Hillman is hopeful that human trials will begin this year. These trials will attempt to determine the number of applications needed to prevent tooth decay permanently. Researchers warn that this does not mean that you can get rid of your tooth brush. Brushing and other forms of dental hygiene would still be recommended to prevent plaque build-up.

 

 

Gene Therapy Reverses Muscular Dystrophy

Using a novel approach, scientists at the Children's National Medical Center and the University of Pittsburgh have successfully repaired muscles in hamsters that were ravaged by a form of muscular dystrophy called limb girdle muscular dystrophy.

In the study, the researchers used a non-replicating adeno-associated virus (AAV) as a gene vector. The virus carried a gene for a component of skeletal muscle called sarcoglycan protein. This protein is not made properly by people suffering from limb girdle muscular dystrophy. AAV is unique in that it does not provoke a response from the immune system and can reside in cells without initiating a response. Once integrated within a cell, it will stay there permanently. This allows the sarcoglycan protein to be produced over the long term.

The AAV vector along with the sarcoglycan gene was injected into the leg muscles of hamsters with limb girdle muscular dystrophy. After approximately a month, the treated muscles were tested and the results were startling. The muscles had increased almost 100 percent in strength and were nearly normal in size. This was the first time that researchers had observed entire muscles being functionally repaired and restored after being ravaged by the effects of muscular dystrophy.

Limb girdle muscular dystrophy causes degeneration of the large muscles attached to the hips and shoulders. It is fatal and has no known effectiby limb girdle muscular dystrophy and perhaps other forms of muscular dystrophy as well.

Can Microbes Help Stem the BP Oil-Spill Disaster?

Current technology used by BP is proving hopelessly inadequate in curbing the tide of oil gushing from beneath the Gulf of Mexico. Now, novel technologies that remain untested at such an incomprehensible scale will be needed in anticipation of years of remediation to resuscitate a dying ecosystem.

“It is of grave concern,” David Kennedy of the National Oceanic and Atmospheric Administration(NOAA), said back in April. “And the efforts that are going to be required to do anything about it, especially if it continues, are just mind-boggling.”

On March 24, 1989, the tanker Exxon Valdez en route from Valdez, Alaska, to Los Angeles ran aground on Bligh Reef in Prince William Sound, Alaska. It spilled approximately 10.9 million gallons of its 53 million gallon cargo of crude oil. Driven by a storm, the oil quickly covered about 1,100 miles of noncontinuous coastline in Alaska. By comparison, as of June 11, 90 million gallons of oil had spurted into the Gulf, according to the new worst-case estimate from the government, which anticipates 20,000–40,000 barrels (about 42 gallons per barrel) leaking daily. This number keeps changing, though and has even gone up to 60,000 barrels a day.

Coast Guard Admiral Thad Allen, who leads the government's relief effort, said in June, “We're no longer dealing with a large, monolithic spill. We're dealing with an aggregation of hundreds of thousands of patches of oil that are going in a lot of different directions.” He noted that while cleaning up the oil spill on the surface will go on for a couple of months after the well is plugged, long-term issues of restoring the environment and the habitats will take years.

Bioremediation may have some role to play in that restoration provided the cure isn’t worse than the disease. Bioremediation involves using microorganisms or their enzymes to return environments altered by contaminants to their original conditions. In the case of oil spills multiple techniques may be used, including the addition of nutrients to the environment to enhance and facilitate crude oil decomposition by specific bacteria or the introduction of oil-eating bacteria. The former approach was used as part of the cleanup effort after the Exxon Valdez spill. The addition of bacteria has been less successful.

Lessons from Exxon Valdez

Bioremediation protocols employed during cleanup of the Exxon Valdez oil spill effectively demonstrated that application of nutrients in the form of fertilizer (nitrogen and phosphorus) could increase oil biodegradation rates. At the time, however, fertilizers used to boost bacterial populations caused some concern, mostly focused on the 2-butoxy-ethanol component in Inipol™ and its potential toxicity to wildlife and cleanup workers. Besides safety guidelines being followed to protect workers during application of fertilizers Inipol and Customblen, wildlife deterrents were used during the first 24 hours when toxicity was of most concern.

Ten days after treatment, the surfaces of the oil-blackened rocks on the shoreline turned white and appeared to be free of surface oil. The striking visual results strongly supported fertilizer application, which sustained higher numbers of oil-degrading microorganisms in oiled shorelines, according to EPA’s 1990 interim report. Additionally, the EPA noted, biodegradation rates were enhanced as evidenced by the chemical changes detected in recovered oil from treated and untreated reference sites.

Oil-Eating Microbes

But while encouraging microbe growth with biostimulation on contaminated shorelines appears useful, unleashing oil-eating microbes themselves has produced less than stellar results. For example, biotreatment using a bacterial culture from Alpha Environmental was deployed following a spill that occurred on June 8, 1990, following an explosion on the Norwegian tanker Mega Borg. An estimated 100,000 barrels of crude oil were burned or released into the Gulf of Mexico, 57 miles southeast of Galveston, during the next week.

Bioremediation tests were conducted on June 15 and 18, 1990. “These were the first tests of a bioremediation agent on an oil spill in open waters in the United States,” the NOAA incident report noted. “The bioremediation agent used was AE BioSea Process, developed by Alpha Environmental. AE BioSea Process contains oil-metabolizing bacteria and nutrients. The results of the tests were inconclusive.”

While the Texas General Land Office said that the bioremediation was effective, independent observations indicated that treated oil changed in physical appearance and may have emulsified as a result of addition of the Alpha product. Chemical analyses on samples from impacted and reference sites failed to demonstrate that treatment with the Alpha product enhanced rates of petroleum biodegradation.

 

Genetic Engineering vs. Experimental Evolution

Evolugate, a Florida company developing microbes for bioremediation, says that adding microbes to the site of a spill hasn’t worked well before because the microbes haven’t been adapted to the specific environment in which they need to survive. The firm is evolving microbes specifically to survive on oil from the Gulf spill in the Gulf environment by maintaining populations of microbial cells under controlled conditions of growth and environment for an indefinite duration. It says that this is a prerequisite for experimentally evolving natural isolates of wild-type species or recombinant strains.

The company grows the microbes in proprietary continuous cell culture vessels to select microbes that have higher proliferation rates under specific conditions. The innovation behind Evolugate’s continuous culture vessels is that they are engineered to prevent microbes from sticking to the walls, a common strategy by which microbes evade selective pressure in other continuous culture technologies.

The Evolugate technology works via partial dilution: As a culture grows and becomes saturated, a small proportion of the grown culture is replaced with fresh medium, allowing the culture to continually grow at close to its maximum population size. Thomas Lyons, Ph.D., principal research scientist and board member of the firm, told GEN that in adapting the microbes for the Gulf oil spill, “we add more microbes every day to bolster genetic diversity.

“When we first started the culture we saw a die-off, and we expected that the dispersants and oil in the Gulf water-containing medium would kill some microbes. But after one week we saw a huge increase in cell density suggesting that adaptive variants arose. Within two weeks we already have robust growth on oil samples taken from the Gulf.

 “The beauty of what we do is that we have built in evolutionary trade-offs: The longer the microbes spend evolving to the oil the less robust they become under other conditions. Once the oil is gone they will lose their competitive advantage and will no longer survive in that environment.”

Dr. Lyons noted that producing such designer microbes through genetic engineering would be hard to pull off. Oil is so full of complicated substances that jamming all the genes needed to digest and metabolize it into a single microbe and then expecting it to reproduce and flourish might be asking too much, he said. Experimental evolution, on the other hand, simultaneously changes metabolic capabilities as well as optimizes growth rates.

He also pointed out that right now the company’s proposal to select and introduce designer oil-eating microbes into the Gulf is in BP’s hands. “It’s in their pipeline, but we are not waiting for a response. We know our approach stands the best chance to make bioremediation work, and we are proceeding accordingly. ”

Genetic engineers did indeed have a shot at enhancing oil-eating microbes. One species of oil eaters in the genus Pseudomonas was used during the Valdez cleanup, but it didn’t work efficiently or very quickly. The oil-eating superbug was developed at General Electric in 1975 by Ananda Mohan Chakrabarty, Ph.D., now distinguished professor of microbiology and immunology at the University of Illinois college of medicine laboratories.

To underscore Dr. Lyons’ point, while there are four oil eaters in this bacterial genus, each uses a different component of the oil as its food source and they all compete with one another when added to the same oil sample. In 1981, Dr. Chakrabarty received a patent on a genetically modified Pseudomonas bacterium that would eat up oil spills, the first patent of its kind; he was the first person to win a patent on a living organism. 

Dr. Chakrabarty and his team inserted plasmids from all four species of the oil eaters and put them into a single microbe. While these plasmids would usually not operate together in the same cell, exposing the cell to ultraviolet light caused the plasmids to join into one that could express components of all four pathways of the original plasmids so that several oil components could be broken down.

 

Time for Creative Thinking

One problem with this creative approach to digestion, however, is that the microbes don’t eat enough nor quickly enough; it takes a lot of them a few days to go through an eyedropper full of oil. There is also concern over what the environmental impact of releasing engineered bacterial strains might be. Additionally, some have pointed out that in the case of oil-eating bacteria, oil companies might not want organisms literally eating their lunch.

Naturally seeping oil in the Gulf already feeds some microbes; low level inputs of hydrocarbons to the oceans, including natural slow oil leaks into the Gulf of Mexico in the form of geological seeps, pine droppings, etc., exist as natural marine ecosystem components. Thus, according to marine biologists, some bacteria within the marine microbial community have evolved the ability to break down hydrocarbons and exploit the considerable energy stored in the chemical bonds of these compounds.

Such organisms aren’t very prevalent, though, since other sources of food are more appealing, pointed out Terry Wade, Ph.D., deputy director of environmental science at Texas A&M University. “It’s like going into the supermarket and instead of buying a steak or a potato, eating the floor tiles.”

Right now ingenuity and insight into using microbes safely to help clean up the oil mess is desperately needed. Sitting around gob-smacked won’t help anything, and environmentalists firmly opposed to the introduction of any organism into the environment will need to suspend disbelief long enough to try desperate measures.

 

The Empty and Misleading Promises of Do-It-Yourself Genetic Tests

"If you could know when and how you would die, would you want to know?" How often have we encountered this question in one form or another, be it between children at the schoolyard or depicted in film and literature? It is a query that resounds within the realm of philosophy: How do we cope with mortality?  Does the certainty of knowing make it better? Or worse? And what if we cannot be given certainty at all? Is it valuable to know how you might die – to engage in an unwinnable contest of crippling probabilities that may or may not offer clues to your fate?

Science can provide no certainties about an individual's medical fate, although some people would like to think otherwise. When the human genome was sequenced, there were definitely some who looked to the nucleotide script as ancient people looked to stars … for answers. We would like to believe that it is that simple – that our DNA sequence can give us the certainty that all of us, at some level of our human consciousness, craves. Am I destined to die of Alzheimer's? Must I ready myself for an arduous battle against cancer? Am I one of the blessed few who will simply drift from this world in my sleep? And while genetic variants have definitely been useful – as with classically Mendelian heritable diseases and biomedical research – by and large, genetic sequence offers little more than "what if's" and "could be's". They may provide an "increased chance" of this or a "decreased chance" of that, but they really don't tell us anything concrete (or useful, for that matter) at all.

That is why I find it particularly worrisome that we are entering the age of affordable, personalized genome sequencing and do-it-yourself genetic tests. While these companies are peddling the promise of knowledge, that is not a commodity that they are actually able to deliver to consumers. Knowing that you have a gene variant that increases your chance for breast cancer, for example, does not mean that you will get breast cancer. Yet, one can easily see how such news could cause undue turmoil among members of the unscientifically-trained public. For what these kits and genome sequencings provide is but a minute glimpse behind the curtain veiling the mechanisms of gene expression. Sure, nucleotides are the "building blocks of life" and all that, but genetic sequence alone will never be capable of providing us with accurate, predictive insight regarding which medical maladies we will acquire.  

For one thing, genetics aren't everything. The "nature versus nurture" argument went by the wayside a long time ago, as it is now recognized that genetic and environmental influences coalesce to determine what occurs within our cells. Secondly, you will recall from your introductory biology classes that DNA sequence is only the first stage of gene expression. One must consider such events as RNA splicing, RNA silencing, and protein modifications (to name a few) if one hopes to attain an accurate assessment of how a gene is expressed. 

Let's also throw in the aspects of cellular context and epigenetic modifications, and you'll soon see that any company that promises to deliver certainty (or even an accurate assessment of probabilities) regarding different medical conditions based solely on DNA sequence is simply preying upon consumers' ignorance. In essence, they are handing consumers a single piece of a 5,000-piece puzzle, telling them that what is displayed on that one fragment is indicative of the pattern of the puzzle as a whole.  

I am not the only one concerned about the less-than-honest promises of at-home genetic tests, as drugstores Walgreens and CVS both canceled their debuts of Pathway Genomics' at-home genetic tests that were scheduled for earlier this month. This was after the Food and Drug Administration started asking for more information from Pathway Genomics about the tests. Just this week Congress got involved, as its House Energy and Commerce Committee launched its own investigation of direct-to-consumer genetic tests. So what does this mean for the future of do-it-yourself genetic testing? Will I ever be able to air-mail a swab of my saliva for my genetic read-out?  Hopefully not. 

The sale of a test that, by its very nature of being direct-to-consumer, can never offer "full disclosure" to the people who buy it should not be permitted. Without extensive disclaimers and interpretation from scientists or medical personnel, consumers don't stand a chance in understanding what the test does and does not tell them about their health. I wouldn't argue that more comprehensive genetic analysis may not be beneficial to people's health in the future, but I think that the only appropriate place for genetic analysis is in a healthcare setting, wherein an informed professional can explain the results to the patient. It is not on a drugstore shelf. And that's one thing about which I am certain.

Recycled LCDs have applications in biomedicine

Recycled LCD TVs could help fight bacterial infections like E coli
Recycled LCD TVs could help fight bacterial infections like E coli

The screens of LCD televisions consist of two sheets of plastic filled with a chemical compound called polyvinyl-alcohol (PVA). PVA – which is also used in wood glues – is biocompatible and has potential uses in biomedicine as tissue scaffolds that help the body regenerate and in pills and dressings designed to deliver drugs to certain parts of the body.

Researchers had already discovered a method to recover PVA from television screens, but found that adding silver nanoparticles gives the compound anti-microbial properties. The PVA/silver compound can destroy both Gram-negative and Gram-positive bacteria like E. coli and some strains ofStaphylococcus aureus.

“In televisions the PVA is a brick-like structure, but under aqueous conditions we converted it to a porous sponge-like material,” principal investigator Dr Avtar Matharu from the University of York told Laboratory News, “This simple reaction under these conditions enabled us to add silver nanoparticles to the PVA, giving it antibacterial properties.”

The team created films that when tested against E. coli inhibited bacterial growth. The research team will now test the PVA-based substance against commercially available compounds to determine relative effectiveness.

“The influence of LCDs on modern society is dramatic – it is estimated that 2.5 billion LCDs are approaching the end of their life and they are the fasting growing waste in the European Union,” said Dr Andrew Hunt from the York Green Chemistry Centre of Excellence.

This research is part of a wider study funded by the Technology Strategy Board to examine the problems posed by LCD waste.

Matharu said sometimes you need to think outside the box: “LCD TVs are just considered waste – you never think to make the link possible medical applications.”

Source: LabNews.co.uk

Award Winning Mayo Clinic Scientist Joins Cardio3 BioSciences

Source:PRNewswire

MONT-SAINT-GUIBERT, BelgiumJuly 14, 2010 /PRNewswire/ –

- Dr. Atta Behfar Recognised With Prestigious Award for Science Behind Cardio3 BioSciences' C-Cure Technology

Cardio3 BioSciences, a leading Belgian biotechnology company specialising in regenerative therapies for the treatment of cardiovascular diseases, today announces that Dr. Atta Behfar is joining its research and development laboratories as Director for Advanced Research. Dr. Atta Behfar, one of the key scientists involved in the development of C-Cure(R), will spend a year at Cardio3 BioSciences on assignment from Mayo Clinic to develop and strengthen the research pipeline.

Dr. Behfar is a member of the clinician investigator program in cardiology at the Mayo Clinic inRochester, Minnesota, USA and has played a key role in the research underlying Cardio3 BioSciences' lead product, C-Cure, a revolutionary stem cell treatment for heart failure. His work was recognised by the Herman K. Gold Young Investigator Award at the Annual American College of Cardiology meeting in March 2010, in GeorgiaAtlanta highlighting the quality of the science behind Cardio3 BioSciences' approach.

C-Cure is designed to reprogram the patient's own stem cells into new heart cells to rebuild the heart. Dr Behfar has played an active part in developing the technology that directs the patient's cells to become cardiopoietic cells – cells 'programmed' to become new heart muscle cells when injected back into the heart of a patient, replacing those cells lost during heart failure and restoring heart function.

Cardio3 BioSciences has recently announced positive three-month safety data and preliminary efficacy results from its Phase II stage clinical trial of C-Cure in heart failure. C-Cure demonstrated a very good safety profile and positive trends in physiological and clinical measures that suggest that C-Cure, as anticipated from animal model data, is acting on heart muscle in a way that could yield important clinical benefits

Dr. Behfar will work with Cardio3 BioSciences' scientific in-house team as of July 1st, 2010, where he will have the opportunity to work directly with the Company as it continues to further develop its unique technology.

Dr. Atta Behfar said: "It is a very exciting time for Cardio3 BioSciences with C-Cure having shown encouraging early results in a clinical setting. I look forward to working with the in-house team as they further advance the product from being a scientific concept towards becoming a therapy that could potentially treat one of the world's greatest unmet medical needs. Many additional treatments may also be leveraged out of the science that lead to C-Cure discovery, and my role will be to fully develop the potential of Cardio3 BioSciences' unique technology."

Dr. Christian Homsy, CEO of Cardio3 BioSciences, added: "We are delighted that Dr Behfar has chosen to come to work with Cardio3 BioSciences and believe this demonstrates not only the quality of the work carried out at Cardio3 BioSciences but also the standard of research inBelgium more generally."

About Cardio3 BioSciences

Cardio3 BioSciences is a leading Belgian biotechnology company specialising in regenerative therapies for the treatment of cardiovascular disease. The Company's lead product, C-Cure(R), is a highly innovative approach to the treatment of heart failure, one of the world's most pressing unmet medical needs. Based on a strategy developed by Cardio3 BioSciences' founders and leveraging technology licensed from Mayo Clinic, C-Cure is designed to reprogram the patient's own stem cells into new heart cells to rebuild the heart.

The Cardio3 BioSciences team has extensive experience in developing and commercialising new pharmaceutical products and medical technologies and the Company's strategy is to drive the clinical development of C-Cure and to market the product itself in major territories.

Cardio3 BioSciences was founded in July 2007 and is based in Mont-Saint-Guibert in the Walloon region of Belgium.

About C-Cure and Heart Failure

Heart failure is a serious and common condition in which the heart cannot pump enough blood through the body, leaving the patient debilitated and unable to conduct a normal life. It can result from heart attacks or a number of other causes. Patients suffering from the condition can experience shortness of breath and extreme exhaustion. It affects 28 million patients worldwide and this number is predicted to double by 2020. Therapies available for chronic heart failure aim at slowing down the disease progression, but with the exception of heart transplant, existing drugs or devices do not cure chronic heart failure.

C-Cure is produced by taking a patient's own stem cells and, through a proprietary process, differentiating them into cardiopoietic cells that can regenerate damaged heart muscle. The cardiopoietic cells are injected into the heart of a patient with heart failure where they are designed to behave identically to those cells lost in heart failure without carrying the risk of rejection, something that has not been achieved with previous cell therapies for this indication. C-Cure is the outcome of multiple years of research conducted at Mayo Clinic (Rochester, Minnesota, USA) and at the Cardiovascular Center in Aalst (Aalst, Belgium).

Disclosures

Mayo Clinic holds equity in Cardio3 BioSciences as a result of intellectual property licensed to the company.

Role of RNA Polymerase in Gene Transcription Demonstrated

ScienceDaily (July 15, 2010) — In all organisms, RNA synthesis is carried out by proteins — known as RNA polymerases (RNAPs) — that transcribe the genetic information from DNA in a highly-regulated, multi-stage process. RNAP is the key enzyme involved in creating an equivalent RNA copy of a sequence of DNA. This transcription is the first step leading to gene expression. While the major steps in RNA synthesis have been known for several decades, scientists have only recently begun to decipher the detailed molecular steps of the complex transcription process.

In research published in the July 1, 2010 online Early Edition of the Proceedings of the National Academy of Sciences, University of Maryland biophysicists Devarajan (Dave) Thirumalai and Jie Chen, along with Rockefeller University collaborator Seth Darst, provide new insight into how the transcription process is initiated and the role that RNA polymerase plays in making this happen. Because the sequence, structure, and function of multi-subunit RNA polymerase are universally conserved in all organisms — from bacteria to humans — understanding the mechanisms of bacterial gene transcription is an important step in deciphering the role of genetics in disease.

"Previously, people didn't know the precise role of RNA polymerase in initiating transcription," explains Distinguished University Professor Dave Thirumalai (Department of Chemistry and Biochemistry and Institute for Physical Science and Technology), "but we showed that it plays an important role in forming the transcription bubble and in the process of bending the DNA to facilitate entry of DNA into the active site. That is the process we described computationally."

Their simulation of the initiation phase of transcription in bacterial RNA polymerase showed a three-step process. It begins when the RNA polymerase binds with transcription promoting regions of DNA. Through interactions with the RNA polymerase, the DNA helix then unwinds, forming an open "bubble" that allows the polymerase access to the exposed DNA sequence to begin transcription. The DNA molecule then bends to relieve stress produced by the opening.

Dr. Jie Chen, who conducted this research while a graduate student in the Chemical Physics program, simulated the transcription bubble formation using a Brownian dynamics-based computer model developed by Dr. Thirumalai's laboratory. "By creating this molecular movie, we can look at the dynamics of RNAP and simulate how it shifts from one structure to another structure," explains Chen. "Our simulation confirms experimental observations, and goes further to establish a clear and active role for RNA polymerase."

Dr. Thirumalai's research group is continuing to study RNA polymerase by looking at the second phase of the transcription process in bacteria and also through models of human transcription.

Undersea Mics Listen for Gulf Whales Threatened by Oil Spill

Recently deployed electronic ears are eavesdropping on whales in the Gulf of Mexico, giving scientists insights into what areas they frequent, population numbers and how they are faring in the oil-ravaged waters.

“Night after night, on TV and on webcams, we saw oil spewing from the bottom of the ocean,” said Christopher Clark, head of the Bioacoustics Research Program (BRP) team at the Cornell Lab of Ornithology. “You wonder, ‘What can we do? What’s the impact of this?’ In the case of marine mammals, we don’t know because we don’t even know what’s there.”

The study will focus on sperm whales and Bryde’s whales (a baleen whale that feeds on plankton), which the National Oceanic and Atmospheric Administration (NOAA) identified as species of concern in the Gulf as a result of the oil spill.

Eavesdropping on whales

To gauge whale health, the Cornell team (in partnership with NOAA) is placing the last of 22 so-called marine autonomous recording units in an arc along the continental shelf of the Gulf at depths of 2,296 to 3,280 feet (700 to 1,000 meters) in both spots affected by the oil and those not yet hit. The arc reflects the area where sperm whales feed.

Though not much is known about Bryde’s whales’ feeding spots, scientists do know the whale makes very low-frequency calls. And in the deep ocean those sounds travel far, suggesting the recorders will also pick up the Bryde’s whale calls.

“Since whales use sounds as a communication, by listening we can tell what species are there, when they are there, and in some cases what are they doing,” said Aaron Rice, BRP’s science director.

Humpbacks and right whales occasionally stray into the Gulf, but they aren’t regulars, Rice said.

Counting whales

After three months of sound recording, a “burn wire” will get tripped, causing this anchor to burn and the units to float to the surface. (That’s why the researchers affectionately call them “pop-ups.”)

The data get turned into spectrograms, or graphs of frequency and time. “In most cases you can get an idea of relative abundance of whales and you can tell which whale” was making emitting the calls, Rice said, adding that one limitation is that when a bunch of whale calls get recorded it’s tricky to tell if it’s one whale making a lot of calls or several whales calling at once.

“But we can tell in many cases – is there one, more than one or a lot, which for assessing impact in the Gulf of Mexico is some of the most important information,” Rice added.

The findings may not tell researchers exactly how the oil is affecting the whales, but they’ll have clues.

They know the oil could directly serve as an irritant or worse, as it could also cause some sort of sickness or even fatality. Indirectly, the oil could kill their food (fish and plankton).

Strandings can also help clarify the reason behind potentially low population counts. “There’s been one stranded sperm whale and a bunch of stranded sea turtles on beaches,” along the Gulf during the oil spill disaster, Rice told LiveScience. “And they’re not showing signs of oil toxicity – there’s no evidence of oil residue in the tissues when they’re necropsied.” (A necropsy is an autopsy performed on an animal.)

However, fish and plankton in the area are showing “quite a bit of oil” in their tissues, Rice added.

Source: LiveScience.com

New Research on Rapidly-Disappearing Ancient Plant Offers Hope for Species Recovery

ScienceDaily (July 14, 2010) — Cycads, "living fossil" descendents of the first plants that colonized land and reproduced with seeds, are rapidly going extinct because of invasive pests and habitat loss, especially those species endemic to islands.

But new research on Cycas micronesica published recently as the cover article in Molecular Ecology calls into question the characterization of these plants as relicts (leftovers of formerly abundant organisms), and gives a glimpse into how the remaining plants — those that survived the loss of more than 90% of their population — can be conserved and managed. By sampling what is left of C. micronesica on Guam, researchers, including some from the American Museum of Natural History, found moderate genetic variation within local populations and different levels of gene flow between populations.

"Cycas micronesica is one of the most ecologically important plants on Guam and nearby islands, and it is now rapidly disappearing," says Angélica Cibrián-Jaramillo, a researcher at the American Museum of Natural History and at The New York Botanical Garden. "But with new genomic tools we developed microsatellite markers to quickly assess individual plants. This technique is ideal for species that need quick answers for conservation reasons." Microsatellite markers are short genetic sequences typically used to determine how individuals are related to each other (kinship) and other population studies.

Cycads have been around for about 300 million years and are among the first spermatophytes, or plants that reproduce with seeds. Although this group's large crowns of feathery compound leaves was once common, cycads now number about 300 species throughout the world, and about half of these are threatened or endangered. C. micronesica is found on four island groups in Micronesia.

Within four years, the millions of C. micronesica on Guam were reduced by more than 90%. The primary culprit was an insect that often parasitizes plants (in this case, a scale) that invaded Guam in 2003, although other invasive species including butterflies and feral pigs are contributing to plant mortality. The invasive species are also spreading to other islands.

"This ecological disaster is typical on islands," says Thomas Marler, professor at the University of Guam. "There has been a cascade of invasive species in a short time. This study will give conservation groups information about how to manage the surviving plants: the most efficient way to establish nurseries and where to collect seeds, and how to reintroduce them if the [invasive] insect is brought under control."

For this study, Marler collected leaf samples from all C. micronesica habitats on Guam, and Cibrián-Jaramillo found 18 genetic populations among 24 locations. The results showed that local populations are not genetically poor but instead have moderate genetic variation with some inbreeding, which is what would be expected in longer-lived plants with similar seed dispersal. The amount of genetic flow between Guam's populations was low but very dynamic within regions in the island, which means that plants are similar genetically and the observed variation points to patterns of seed dispersal. Cycas micronesica plants in the north are more likely to be related to each other, while populations in the south are genetically different from each other. This contrast is most likely due to southern Guam's more fragmentary forests, more rivers for seed transportation (C. micronesica seeds are one of the few cycad seeds that float), and the smaller size of seeds, which can be dispersed to greater distances.

"We hope that these results from the plant perspective will fit into the management of invasive insects in general, which is one of the most important drivers of biodiversity loss worldwide and very costly economically," says Rob DeSalle, curator at the American Museum of Natural History who works in the Sackler Institute for Comparative Genomics.

In addition to Cibrián-Jaramillo, Marler, and DeSalle, authors of this paper include Aidan Daly of the Museum's Sackler Institute for Comparative Genomics and Eric Brenner of New York University. The research was funded by the U.S. Department of Agriculture and the Lewis B. and Dorothy Cullman Program for Molecular Systematics at the American Museum of Natural History and The New York Botanical Garden.

Heart to Heart Tool

We all know the statistics: millions suffer from heart disease, and many suffer heart attacks. Even more alarming is the fact that by some estimates more than 350,000 people die from so-called "sudden death" after a heart attack. Researchers have been baffled by the exact nature and cause of these deaths. Last week, scientists at the University of North Carolina Chapel Hill unveiled a promising new modeling procedure which may shed some light on the mechanisms associated with heart attacks and sudden death.

This new system involved cultured heart cells. In a heart attack, some cells become deprived of oxygen while others continue to receive sufficient oxygen. The region between these two types of cells, called the border zone, is simulated in the cultured model. Since the culture focuses on the interactions in the border zone, it could be very helpful in studying arrhythmias. Arrhythmias are irregularities in the heartbeat usually associated with decreased blood flow in the coronary arteries.

The complex interactions within a particular organism and the size of the actual zone have made animal models particularly difficult in studying the border zone. Likewise, single cells don't display the border irregularities. By using a culture of cells, the research team was able to overcome both limitations. The border zone can be produced and the interactions are essentially isolated for practical purposes.

The cultures appear to be stable for a couple of hours, thus allowing the team to do basic time-based studies.

Since the causes and mechanisms associated with sudden death are so poorly understood, researchers are optimistic that this new modeling system will shed some light on sudden death. By focusing on the internal changes associated with cells and the resulting interactions, the team believes that the culture model will be successful.

What do you think? Might this new technique be helpful in reducing the instances of sudden death? What other therapies and/or procedures might be used to produce a synergistic effect? Come over to the Biology Forum and share your thoughts, opinions, and feelings.

Mylotarg Withdrawal Raises Questions

Pfizer agreed today to withdraw its therapy for acute myeloid leukemia, Mylotarg (gemtuzumab ozogamicin), from the U.S. market, effective October 15. The reason? It didn’t work, and people died. 

So far, the story makes sense. Developed by Wyeth, the drug was fast-tracked to treat patients ages 60 and older with recurrent AML who were not candidates for other chemotherapy. It was approved by the FDA in May 2000 based upon a surrogate endpoint, because it treated a serious disease that had no other viable therapy. 

Four years later, a confirmatory trial was begun to confirm the results of the 142 patients who participated in the three previous clinical trials. Given the circumstances, the failure and subsequent withdrawal makes sense. 

What doesn’t make sense is what comes next. Wyeth stopped the 2004 trial early because patients experienced no clinical benefit and died in greater numbers than those receiving chemotherapy alone. 

So, why did it take so long to withdraw the drug?  Why is Mylotarg being withdrawn only for the U.S. market? Why does the withdrawal become effective October 15, three and one half months from now? 

Why are patients who are on Mylotarg allowed to continue a therapy that, according to the FDA, “demonstrates no clinical benefit?”