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GeoVax Labs, Inc. (OTC Bulletin Board: GOVX), an Atlanta based, publicly traded biopharmaceutical company specializing in the prevention and treatment of infectious diseases, provided an operational update on the company’s progress towards entering Phase 2 preventative human clinical trial testing and plans to proceed into therapeutic human trials with its AIDS vaccine. Five successful human trials evaluating GeoVax AIDS vaccines have previously been reported.

Planned Phase 2 Human Clinical Trial for Prevention of AIDS

The Company’s Phase 2 trial, conducted by the U.S. National Institutes of Health (NIH) supported HIV Vaccine Trials Network (HVTN), will involve 225 healthy volunteers from the United States and South America, and will further evaluate the safety and immunogenicity of the GeoVax preventative vaccine (vaccine administered prior to infection with the HIV virus). In Phase 1 trials, both 1/10th dose and full dose of the GeoVax vaccine elicited anti-HIV T-cells, whereas the full dose was required to elicit good frequencies of antibody to the HIV Envelope glycoprotein. The larger Phase 2 human trial will broaden the base of safety and immunogenicity data for the full dose of the GeoVax AIDS vaccine with a view to protecting recipients from developing AIDS should they be exposed to the virus. The planned Phase 2 human clinical trial is currently scheduled to start early this fall, subject to FDA approval.

Preclinical Data for Use of Vaccine Technology as an AIDS Therapeutic Human Clinical Trials in Planning Stages GeoVax also announced summary data from a pilot study on therapeutic vaccination in simian immunodeficiency virus (SIV) infected non-human primates with the SIV prototype for the GeoVax AIDS vaccine. In this small pilot study, conducted by Dr. Amara at Emory University, two non-human primates were infected with SIV. At 12 weeks post SIV infection, conventional anti-viral drug therapy was given to the primates to reduce the viral RNA infection levels to very low levels creating a non progressor status for the primate. Then the SIV prototype vaccine for the GeoVax AIDS vaccine was administered. Six weeks following the final vaccination, anti-viral drug treatment was stopped and the animals were monitored to determine whether the vaccine could control the SIV infection during the absence of the drugs.

The outstanding results from the study revealed the vaccine controlling the infection in the absence of drugs. In one primate, the reduction in viral levels over pre-drug treatment and vaccination levels was 1000 times. In the other, the reductions in viral levels were 100 times. The excellent control of the virus infection in the absence of drug treatment was associated with the vaccine raising the types of CD4 and CD8 T cells that are found in the rare individuals who spontaneously control their HIV infections.

Based on these excellent results, planning for a therapeutic trial in infected and drug treated humans has been initiated. The intent of therapeutic vaccination is for the vaccine to “control” HIV virus levels in infected individuals to very low levels thus blocking the development of AIDS. Successful therapeutic AIDS vaccination programs with GeoVax vaccines would lead to reduction in the use of costly anti-HIV medications and their often harmful side effects.

Dr. Harriet Robinson, GeoVax Co-founder and Senior V.P. of Research and Development, commented, “I had not anticipated the extent of vaccine control that was achieved in the already infected non-human primates. These are highly promising results that need to be extended into infected humans to see if the vaccine can be used to reduce the need for taking drugs. The results also warrant more extended studies in already infected non-human primates to explore parameters that both limit and enhance the ability for a vaccine to displace the need for drugs.”

Dr. Robert McNally, CEO and President of GeoVax Labs, Inc., emphasized, “It is noteworthy to mention that the GeoVax AIDS vaccines being tested in the preclinical therapeutic trial is the same basic vaccine administered in the Company’s human trials testing for a preventative use of the vaccine, vaccinating people before infection to prevent the development of AIDS should they become infected. Thus, a “one for two” vaccine could be a breakthrough solution for the company and the world, saving millions of dollars in redundant development costs and years of testing time by utilizing safety data already achieved in Phase 1 preventative human trials. More important, time to market could be significantly reduced, saving lives much sooner than otherwise.”

Further, GeoVax’s management is pleased to report that the company is currently engaged in negotiations with a NIH sponsored trial network to administer, conduct and co-sponsor GeoVax’s Therapeutic human trial program. Management expects to receive approval for undertaking formal protocol development in the near future and will report more detailed plans accordingly.

“From an operational standpoint, we are very pleased with the overall progress of the company,” stated Dr. Robert McNally. “Progress with ongoing preventative vaccine trials and now the potential to address therapeutic use of the vaccine gives GeoVax an expanding role in the fight to control AIDS.”

About GeoVax Labs, Inc.

GeoVax Labs, Inc. is a biotechnology company, established to develop, manufacture, license and commercialize human vaccines for diseases caused by HIV-1 (Human Immunodeficiency Virus) and other infectious agents. GeoVax’s AIDS vaccine technology is the subject of 20 issued or filed patent applications. GeoVax AIDS vaccines are designed for use in uninfected people to prevent Acquired Immunodeficiency Disease (AIDS), caused by the virus known as HIV-1, should the person ever become infected. GeoVax AIDS vaccines also may be effective as therapeutics, treatment of people already infected with AIDS virus.

GeoVax’s core AIDS vaccine technologies were developed by Dr. Harriet Robinson, Senior V.P. of Research and Development, through a collaboration of colleagues at Emory University’s Vaccine Center, the National Institutes of Health (NIH), The Centers for Disease Control and Prevention (CDC) and GeoVax.

GeoVax AIDS vaccines have moved forward in human clinical trials conducted by the HIV Vaccine Trials Network (HVTN) based in Seattle, Washington. The HVTN, funded through a cooperative agreement with the National Institutes of Health (NIH), is the largest worldwide clinical trials program dedicated to the development and testing of AIDS vaccines. Preclinical work enabling evaluation of GeoVax DNA and MVA vaccines was funded and supported by NIAID, which provided additional support to GeoVax AIDS vaccine development program with a $15 million IPCAVD grant awarded in late 2007.

Safe Harbor Statement: All statements in this news release, not statements of historical fact, are forward-looking statements. These statements are based on expectations and assumptions on the date of this press release and are subject to numerous risks and uncertainties which could cause actual results to differ materially from those described in the forward-looking statements. Risks and uncertainties include, but are not limited to, whether: GeoVax can develop and manufacture these vaccines with the desired characteristics in a timely manner, GeoVax’s vaccines will be safe for human use, GeoVax’s vaccines will effectively prevent AIDS in humans, vaccines will receive regulatory approvals necessary to be licensed and marketed, GeoVax raises required capital to complete vaccine development, there is development of competitive products that may be more effective or easier to use than GeoVax’s products, and other factors over which GeoVax has no control. GeoVax assumes no obligation to update these forward-looking statements, and does not intend to do so. Certain matters discussed in this news release are forward-looking statements involving certain risks and uncertainties including, without limitation, risks detailed in the Company’s Securities and Exchange Commission filings and reports.

GeoVax Labs, Inc.
http://www.geovax.com

Resolvyx Pharmaceuticals, Inc., the leading resolvin therapeutics company, today announced that a research team led by a Resolvyx scientific advisor and a company co-founder has demonstrated that the resolvin E1 (RvE1) effectively suppresses IL-23 and IL-17, two key inflammatory mediators of chronic inflammatory disease, in a preclinical model of asthma. RvE1 is the active ingredient in RX-10001, one of Resolvyx’s leading clinical candidates. The paper, titled “Resolvin E1 regulates interleukin 23, interferon-? and lipoxin A4 to promote the resolution of allergic airway inflammation,” published in the journal Nature Immunology.

“This study demonstrates that RvE1 potently suppresses IL-23 and IL-17, which are critical in regulating airway inflammation in chronic asthma,” said Bruce D. Levy, M.D., lead author of the study, scientific advisor to Resolvyx and Associate Professor of Medicine at the Department of Internal Medicine Pulmonary and Critical Care Medicine Division, Brigham and Women’s Hospital. “As the IL-23/IL-17 pathway has been increasingly linked to chronic inflammation, tissue remodeling, pathological neovascularization and bone loss, these results have implications for the therapeutic potential of resolvins in a range of human diseases.”

The research team evaluated RX-10001 (RvE1) in a well established mouse model of asthma and showed that RX-10001 (RvE1), when administered at the peak of inflammation, significantly suppressed airway inflammation and prevented lung hyperreactivity. The levels of IL-17 and IL-23 were reduced by 70% and 60%, respectively, contributing to a greater than 80% reduction in infiltrating leukocytes including eosinophils, which are a major driver of the allergic airway hyper-responsiveness.

“The finding that RX-10001 suppresses IL-23 and IL-17 suggests that resolvins can potentially treat not only asthma but also inflammatory bowel disease, rheumatoid arthritis, atherosclerosis and other diseases,” said Charles Serhan, Ph.D., co-author of the study, co-founder of Resolvyx and Director of the Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women’s Hospital. “Given their broad potential to treat human disease, it is very exciting that Resolvyx is advancing resolvin drug candidates into clinical trials in the coming months.”

Resolvyx also has conducted preclinical studies with RX-10001 (RvE1) in asthma and other systemic inflammatory diseases. Resolvyx has announced plans to initiate human clinical trials for RX-10001 in the first half of 2009.

About Resolvins

Resolvins are a recently discovered family of naturally-occurring, small molecule lipid mediators that can be targeted to treat a wide range of diseases. In particular, resolvins act to protect healthy tissue during an immuno-inflammatory response to infection, injury or other environmental challenge, and then act to resolve inflammation and promote healing after the insult has passed. Resolvins are shown to be highly potent and efficacious in pre-clinical models of asthma, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, dry eye and retinal disease, among others.

Resolvins are potential drug candidates to treat a broad range of acute and chronic diseases caused by a failure to resolve the inflammatory response and restore immune homeostasis. Such diseases include auto-immune diseases (like Crohn’s disease, psoriasis and rheumatoid arthritis), allergic diseases (like asthma) and chronic inflammatory diseases (like atherosclerosis, degenerative retinal diseases, chronic dry eye and Alzheimer’s disease). Resolvins offer an entirely novel biological approach to treating significant inflammatory diseases, with a decreased potential for immuno-suppression.

About Resolvyx Pharmaceuticals

Resolvyx Pharmaceuticals is a privately-held biopharmaceutical company dedicated to the discovery, development and commercialization of resolvins, a novel class of therapies to treat inflammatory diseases and their complications. Resolvyx’s drug R&D programs are focused on characterizing and developing resolvin-based compounds. With its experienced management team, world-class scientists and leading investors, Resolvyx is well-positioned to capitalize on its extensive portfolio of more than 55 patents and applications. The company’s headquarters are in Bedford, Massachusetts.

http://www.resolvyx.com.

Thyroid cancer that has spread to distant sites has a poor prognosis, but an experimental drug that inhibits tumor blood vessel formation can slow disease progression in some patients, a research team led by investigators from The University of Texas M. D. Anderson Cancer Center reports in the July 3rd edition of The New England Journal of Medicine.

The investigational drug, motesanib diphosphate, is a VEGF inhibitor, a biologic agent that targets receptors on a protein known as vascular endothelial growth factor (VEGF). VEGF is instrumental in angiogenesis (formation of new blood vessels), a process that allows tumors to grow and spread.

Study lead author Steven I. Sherman, M.D., chair and professor of M. D. Anderson’s Department of Endocrine Neoplasia and Hormonal Disorders, noted strong evidence that VEGF receptors play an important role in metastatic thyroid cancer, a disease with few treatment options.

Read more ….

MedicalNewsToday.com

High-dose injections of vitamin C, also known as ascorbate or ascorbic acid, reduced tumor weight and growth rate by about 50 percent in mouse models of brain, ovarian, and pancreatic cancers, researchers from the National Institutes of Health (NIH) report in the August 5, 2008, issue of the Proceedings of the National Academy of Sciences. The researchers traced ascorbate’s anti-cancer effect to the formation of hydrogen peroxide in the extracellular fluid surrounding the tumors. Normal cells were unaffected.

Natural physiologic controls precisely regulate the amount of ascorbate absorbed by the body when it is taken orally. “When you eat foods containing more than 200 milligrams of vitamin C a day–for example, 2 oranges and a serving of broccoli–your body prevents blood levels of ascorbate from exceeding a narrow range,” says Mark Levine, M.D., the study’s lead author and chief of the Molecular and Clinical Nutrition Section of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the NIH. To bypass these normal controls, NIH scientists injected ascorbate into the veins or abdominal cavities of rodents with aggressive brain, ovarian, and pancreatic tumors. By doing so, they were able to deliver high doses of ascorbate, up to 4 grams per kilogram of body weight daily. “At these high injected doses, we hoped to see drug-like activity that might be useful in cancer treatment,” said Levine.

Read more ….

MedicalNewsToday.com

Tiny strands of genetic material called RNA - a chemical cousin of DNA - are emerging as major players in gene regulation, the process inside cells that drives all biology and that scientists seek to control in order to fight disease.

The idea that RNA (ribonucleic acid) is involved in activating and inhibiting genes is relatively new, and it has been unclear how RNA strands might regulate the process.

In a new study available online and in a future issue of Nature Structural and Molecular Biology, RNA experts at UT Southwestern Medical Center found that, contrary to established theories, RNA can interact with a non-gene region of DNA called a promoter region, a sequence of DNA occurring spatially in front of an actual gene. This promoter must be activated before a gene can be turned on.

“Our findings about the underlying mechanisms of RNA-activated gene expression reveal a new and unexpected target for potential drug development,” said Dr. David Corey, professor of pharmacology and biochemistry at UT Southwestern and one of the senior authors of the study.

Genes are segments of DNA housed in the nucleus of every cell, and they carry instructions for making proteins. Faulty or mutated genes lead to malfunctioning, missing or overabundant proteins, and any of those conditions can result in disease. Scientists seek to understand the mechanisms by which genes are activated, or expressed, and turned off in order to get a clearer picture of basic cell biology and also to develop medical therapies that affect gene expression.

In previous studies, Dr. Corey and Dr. Bethany Janowski, assistant professor of pharmacology at UT Southwestern and a senior author of the current study, have shown that tiny strands of RNA can be used to activate certain genes in cultured cancer cells. Using strands of RNA that they manufactured in the lab, the researchers showed that the strands regulate gene expression by somehow perturbing a delicate mixture of proteins that surround DNA and control whether or not genes are activated.

Until now, however, it was not clear exactly how the synthetic RNA strands affected that mix of regulating proteins.

In the current study, also carried out in cancer cell cultures, the UT Southwestern research team discovered an unexpected target for the manufactured RNA. The RNA did not home in on the gene itself, but rather on another type of RNA produced by the cell, a so-called noncoding RNA transcript. This type of RNA is found in association with the promoter regions that occur in front of the gene. Promoter regions, when activated, act essentially as a “start” command for turning on genes.

The researchers found that their man-made RNA strand bound to the RNA transcript, which then recruited certain proteins to form an RNA-protein complex. The whole complex then bound to the promoter region, an action that could then either activate or inhibit gene expression.

“Involvement of RNA at a gene promoter is a new concept, potentially a big new concept,” Dr. Janowski said. “Interactions at gene promoters are critical for understanding disease, and our results bring a new dimension to understanding how genes can be regulated.”

Until recently, many scientists believed that proteins alone control gene expression at promoters, but Drs. Corey and Janowski’s results suggest that this assumption is not necessarily true.

“By demonstrating how small RNAs can be used to recruit proteins to gene promoters, we have provided further evidence that this phenomenon should be in the mainstream of science,” Dr. Corey said.

Although using synthetic RNA to regulate gene expression and possibly treat disease in humans is still in the future, Dr. Corey noted that the type of man-made RNA molecules employed by the UT Southwestern team are already being used in human clinical trials, so progress toward the development of gene-regulating drugs could move quickly.

Other researchers from UT Southwestern involved in the research were lead author and student research assistant Jacob Schwartz; student research assistant Scott Younger; and research associate Ngoc-Bich Nguyen. Researchers from the University of Western Ontario and ISIS Pharmaceuticals also participated.

The research was supported by the National Institutes of Health and the Welch Foundation.

Researchers have developed what they believe is the first new mechanism in nearly 20 years for inhibiting a common target used to treat all HIV patients, which could eventually lead to a new class of AIDS drugs.

Researchers at the University of Michigan used computer models to develop the inhibiting compound, and then confirmed in the lab that the compound does indeed inhibit HIV protease, which is an established target for AIDS treatment. The protease is necessary to replicate the virus, says Heather Carlson, U-M professor of medicinal chemistry in the College of Pharmacy, and principal investigator of the study.

Carlson stresses this is a preliminary step, but still significant.

“It’s very easy to make an inhibitor, (but) it’s very hard to make a drug,” said Carlson, who also has an appointment in chemistry. “This compound is too weak to work in the human body. The key is to find more compounds that will work by the same mechanism.”

What’s so exciting is how differently that mechanism works from the current drugs used to keep the HIV from maturing and replicating, she says. Current drugs called protease inhibitors work by debilitating the HIV-1 protease. This does the same, but in a different way, Carlson says.

A protease is an enzyme that clips apart proteins, and in the case of HIV drugs, when the HIV-1 protease is inhibited it cannot process the proteins required to assemble an active virus. In existing treatments, a larger molecule binds to the center of the protease, freezing it closed.

The new mechanism targets a different area of the HIV-1 protease, called the flap recognition pocket, and actually holds the protease open. Scientists knew the flaps opened and closed, but didn’t know how to target that as a mechanism, Carlson says.

Carlson’s group discovered that this flap, when held open by a very small molecule—half the size of the ones used in current drug treatments—also inhibits the protease.

In addition to a new class of drugs, the compound is key because smaller molecules have better drug-like properties and are absorbed much more easily.

“This new class of smaller molecules could have better drug properties (and) could get around current side effects,” Carlson said. “HIV dosing regimes are really difficult. You have to take medicine several times in the day. Maybe you wouldn’t have to do that with these smaller molecules because they would be absorbed differently.”

Kelly Damm, a former student and now at Johnson & Johnson, initially had the idea to target the flaps in this new way, Carlson says.

“In a way, this works like a door jam. If you looked only at the door when it’s shut, you’d not know you could put a jam in it,” she said. “We saw a spot where we could block the closing event, but because everyone else was working with the closed form, they couldn’t see it.”

For more information on Carlson, click here.

College of Pharmacy: http://www.umich.edu/~pharmacy/

Source: Laura Bailey
University of Michigan

Complexities of Clinical Trials (34 minutes)

Courtesy of the Transverse Myelitis Association - http://www.myelitis.org/rnds2004/

2004 Rare Neuroimmunologic Disorders Symposium

Lecture by J. McArthur, MBBS, MPH

Scientists at The Australian National University are a step closer to understanding the rare Hartnup disorder after discovering a surprising link between blood pressure regulation and nutrition that could also help to shed light on intestinal and kidney function.

The team from the University’s School of Biochemistry and Molecular Biology together with colleagues from the University of Sydney set out to study nutrient uptake in the intestine and discovered an essential role of a protein called ACE2 in the process. ACE proteins cut off a small part of a precursor molecule generating a hormone, which regulates blood pressure. ACE inhibitors are widely prescribed drugs that reduce the risk of heart failure and protect against the long-term effects of diabetes.

Two versions of the protein are known as ACE1 and ACE2. ACE1 is targeted by the blood pressure reducing drugs, but until now the role of ACE2 has been less clear. What the researchers found was a completely different role for ACE2 in nutrition.

“Protein forms up to 20 per cent of our nutrition,” said one of the authors of the report, Professor Stefan Bröer. “Before it can be used by the human body, protein is split into its subunits called amino acids. The amino acids are then removed from the intestine by specialised cells which are endowed with a large number of transporters moving nutrients from the intestine into cell.

“Instead of tailoring a specific hormone, ACE2 cuts into proteins releasing amino acids from the intestine into cells. Additionally, we found that ACE2 was also important to endow the cell with transporters” he said.

The research shows that a failure of certain transporters to make contact with ACE2 can cause Hartnup disorder - where amino acid absorption in the intestine is impaired resulting in neurological problems and a skin rash in children.

The paper, published in The Federation of American Societies for Experimental Biology (FASEB) Journal, also highlights the variety of roles that proteins can play.

“The results demonstrate a connection between blood pressure regulation and nutrition and also show that proteins in the body can serve several functions. This explains why drugs can have surprising side effects if the target carries out several functions.

“The results of this study will help understanding intestinal and kidney function, which are affected in common disorders such as diabetes and celiac disorder,” said Professor Bröer.

Source: Martyn Pearce
Research Australia

A Paradigm Shift in Pharmaceutical Clinical Trials - (6 minutes)

Taren Grom, Editor of PharmaVOICE magazine talks with Ira Spector, Vice Chief of Clinical Operations at Wyeth, about improving clinical tria…all » Taren Grom, Editor of PharmaVOICE magazine talks with Ira Spector, Vice Chief of Clinical Operations at Wyeth, about improving clinical trials in the pharmaceutical industry. Part of the PharmaVOICE Webcast Network.

Research, led by a Virginia Tech chemist, may someday help natural-products chemists decrease by years the time it takes to develop certain types of medicinal drugs. The research by T. Daniel Crawford, associate professor of chemistry, involves computations of optical rotation angles on chiral non-superimposable molecules

Many chiral molecules are important for medical treatment for illnesses ranging from acid-reflux to cancer. The term “chiral” means that two mirror images of a molecule cannot be superimposed onto each other. In other words, some are “left-handed” and some are “right-handed.”

“Most drugs have this handedness property,” Crawford said, “and for many of these drugs, even though both hands can cause a reaction, it is a situation where one hand does a good thing and one does a bad thing.” He used thalidomide as an example. A mixture of both hands of the drug was used in the late 1950s and early 1960s to treat morning sickness in pregnant women. Later studies revealed that, while one of the two hands acted as the desired sedative, the other hand was found to cause significant birth defects. Thalidomide was never approved by the FDA in the United States and was eventually taken off the market in Europe.

For chemists, therefore, it is often vital to determine which hand of a molecule they are using. In other words, when you have a sample of a chiral molecule, how do you distinguish between the left and right hand?

This is where a technique called polarimetry comes in to play. By shooting plane-polarized light through a sample of one hand, the chiral molecule in question will rotate to a characteristic angle either clockwise or counterclockwise, and the two hands of a chiral molecule produce opposite rotations.

“So if we figure out the direction and rotation of the light or each hand, we have a frame of reference for determining whether we have the left or right hand of a molecule,” Crawford said.

The problem with this method is that synthesizing the two hands of chiral molecules is often extremely time consuming. “It can take anywhere from weeks to years,” Crawford said.

Crawford’s research applies the theory of quantum mechanics to devise computational methods in order to eliminate having to create a synthetic molecule. “The hope is that this will allow us to calculate things like optical rotation very accurately,” he said. “So when an organic chemist has a molecule and doesn’t know if it is left- or right-handed, we can calculate that directly on the computer.”

Crawford said the ultimate goal in his research is to be able to provide organic chemists with computational tools to determine the handedness of a particular molecule they are working with. He said that such tools could speed up the drug development process by years.

The research titled, The Current State of ‘Ab Initio’ Calculations of Optical Rotation and Electronic Circular Dichcoism Spectra, by Crawford and Mary C. Tam of Virginia Tech and Mica Abrams of the University of Central Arkansas, appeared as the cover article in the November 2007 Journal of Physical Chemistry A. Get the complete article at: http://pubs.acs.org/cgi-bin/article.cgi/jpcafh/2007/111/i48/html/jp075046u.html

About the College of Science

The College of Science at Virginia Tech gives students a comprehensive foundation in the scientific method. Outstanding faculty members teach courses and conduct research in biology, chemistry, economics, geosciences, mathematics, physics, psychology, and statistics. The college is dedicated to fostering a research intensive environment and offers programs in many cutting edge areas, including those in nanotechnology, biological sciences, information theory and science, and supports the university’s research initiatives through the Institute for Critical Technologies and Applied Sciences, and the Institute for Biomedical and Public Health Sciences. The College of Science also houses programs in intellectual property law and pre-medicine.

Virginia Tech (Virginia Polytechnic Institute and State University)
Room 1, Media Bldg. (0109)
Blacksburg, VA 24061
United States
http://www.vt.edu

Researchers at the University of Edinburgh and IBM are using powerful computing technology - including the world’s most powerful supercomputer, Blue Gene - in a new approach to designing drugs that inhibit infection by the HIV virus.

The project, which has been welcomed by First Minister Alex Salmond, is focused on how the human HIV-1 virus attaches to cells in the body. Researchers are examining a fragment of the surface protein of the virus, known as a peptide, which is crucial in stimulating the body’s immune response to viral attack. Understanding the structure and behaviour of the peptide will allow for drugs to be designed which can target this infection process.

Most HIV therapies so far have focused on the behaviour of the virus in the body after infection has taken place, when the virus multiplies and then spreads through the bloodstream. This project aims to target the infection process itself.

The project is a collaboration between the University of Edinburgh, IBM Watson Research Centre in New York and the National Physical Laboratory in Middlesex.

Jason Crain, of the University of Edinburgh’s School of Physics and Divisional Head of Science at the National Physical Laboratory, said: “This is a new approach to drug design - we are using sophisticated algorithms coupled with experimental techniques to design improved molecular therapies, and we can capitalise on enormous computing power to do this efficiently and rationally.”

The University of Edinburgh is at the forefront of advances in high performance computing and provides the widest range of supercomputer facilities of any university in Europe.

IBM Researcher Glenn Martyna said: “One of the great challenges in the medical community is to find a vaccine for the HIV virus. By combining the experimental research of the University of Edinburgh and the simulation capabilities of the world’s most powerful supercomputer, IBM’s Blue Gene, we just might get much closer to that goal.”

During Scotland Week in America, First Minister Alex Salmond said: “This life sciences collaboration, between one of Scotland’s leading universities and one of America’s biggest corporations, is a first class and positive example of the sort of connections we are trying hard to encourage and support.”

“I am delighted that through the efforts of Scottish Enterprise and Scottish Development International, we have been able to play a part in bringing this exciting project to the key stage it is at.”

University of Edinburgh is one of the top 10 Universities in Europe, one of the top 30 in the world (Times Higher World University Rankings)

University of Edinburgh

For quite some time, DNA, the stuff our genes are made of, has also been considered the building material of choice for nanoscale objects. A team led by Gunter von Kiedrowski at the Ruhr University in Bochum has now made a dodecahedron (a geometric shape with twelve surfaces) from DNA building blocks. As reported in the journal Angewandte Chemie, these objects are formed in a self-assembly process from 20 individual trisoligonucleotides, building blocks consisting of a “branching junction” and three short DNA strands.

A regular dodecahedron is a geometric shape made of 12 pentagons of equal size, three of which are connected at every vertex. This results in a structure with 30 edges and 20 vertices. In order to produce a hollow dodecahedral object from DNA, the researchers used 20 “three-legged” building blocks (three DNA strands connected together at one point). The centers of these building blocks represent the vertices of the dodecahedron. The three edges projecting from each vertex are formed when a single strand of DNA converts two neighboring bridging components into a double strand.

In order for this process to result in a dodecahedron and not some other random geometric object, all of the DNA strands must have a different sequence. Among these, there must, however, be pairs of complementary strands that can bind to each other.

By using a computer program, the researchers identified a set of 30 independent, 15-base-pair-long, double-stranded DNA sequences with similar physical properties. The double-stranded sequences were assigned to the individual edges of the dodecahedron and to specific vertices for termination. It was then determined which three single-stranded sequences needed to be attached to each three-legged junction for the predetermined structure to form.

The team synthesized the 20 computed trisoligonucleotides by means of a solid-phase synthesis. The three DNA strands were always attached by way of an aromatic six-membered carbon ring. When mixed in equal parts in a buffer solution, these building blocks do aggregate to form the expected product: regular dodecahedra. Atomic force microscopy images reveal them to be uniform particles with a diameter of about 20 nm. Under pressure, the dodecahedra are quite flexible, the can be deformed like “soft balls” without incurring any damage.

If the trisoligonucleotides are equipped with pendant “arms”, the dodecahedra can be outfitted with additional functional molecules. In this way, highly complex nanoconstructs, resembling little viruses in shape and size, should be accessible in the future. Potential applications range from medical diagnostics to nanoelectronics.

Günter von Kiedrowski
Ruhr-Universität Bochum
Germany
Angewandte Chemie International Edition

Synvista Therapeutics, Inc. (Amex: SYI) announces data from a study of diabetic mice with the Haptoglobin 2-2 genotype that show impairment in the clearance of the Haptoglobin (Hp)-Hemoglobin (Hb) complex may result in a modification of high-density lipoprotein (HDL) structure and defective reverse cholesterol transport. These findings, which were presented at the 57th Annual Scientific Sessions of the American College of Cardiology in Chicago, suggest the value of Haptoglobin testing in people with diabetes in order to ensure more successful treatment in the prevention of cardiovascular events (such as heart attack and stroke).

“These data from a validated animal model support our belief that Haptoglobin testing may help physicians tailor optimal therapy for patients with diabetes who may be at risk for cardiovascular events. The transport of cholesterol out of atherosclerotic plaque may be an important mechanism of stroke and heart attack prevention. Characterizing the functional impairment of HDL may help us understand how to intervene in Hp2-2 diabetic patients,” said Noah Berkowitz, M.D., Ph.D., President and Chief Executive Officer of Synvista Therapeutics, which is developing a diagnostic product to identify Haptoglobin types. “As with previous studies of diabetic patients exhibiting markedly elevated cardiovascular risk, we believe that these findings support the notion of testing for Haptoglobin and treating the appropriate diabetic patients (Hp2-2) with vitamin E.”

In the study, researchers assessed clearance of Hb by Hp in diabetic mice that were also tested for Hp type. The study showed that in these mice, the combination of diabetes and the Hp2-2 genotype was associated with a two-to-three-fold increase in the half-life of the Hp-Hb complex compared to other Hp types. Further, a greater than 10-fold increase was found in the association of Hp-2-Hb and HDL in these mice. The study also demonstrated that vitamin E supplementation prevented the impairment of reverse cholesterol transport in diabetic mice with the Hp2-2 genotype.

About Haptoglobin 2-2

The Hp protein is polymorphic in humans, occurring with two alleles, 1 and 2, existing at the Hp genetic locus. Three phenotypes linked to the three genotypes, Hp 1-1, Hp 1-2 and Hp 2-2, can be identified using an ELISA assay. In multiple independent prospective longitudinal studies of more than 20,000 individuals, it has been established that the Haptoglobin genotype is an independent risk factor for cardiovascular disease, with a specific relationship to patients with diabetes mellitus. After accounting for conventional cardiovascular risk factors and diabetes characteristics in these studies, research has demonstrated that there is a 2-5 fold increased risk of cardiovascular disease in people with both diabetes and the Hp 2-2 genotype (approximately 40 percent of all diabetes patients).

About Synvista Therapeutics

Synvista Therapeutics is a biopharmaceutical company developing drugs to treat and prevent cardiovascular disease and nephropathy in people with diabetes. The Company believes it has identified several product candidates that represent novel approaches to some of the largest pharmaceutical markets. The Company’s portfolio includes orally bioavailable, organoselenium mimics of glutathione peroxidase. These compounds metabolize lipid peroxides and have the potential to limit myocardial damage subsequent to a myocardial infarction. The Company is developing a clinical diagnostic test, based on cardiovascular risk assessment, using Haptoglobin characterization, to identify patients at high risk for cardiovascular complications of diabetes.

Synvista Therapeutics also is developing alagebrium, a proposed breaker of AGEs for the treatment of diastolic heart failure. This disease represents a rapidly growing market of unmet medical need, particularly common among diabetic patients. Alagebrium has demonstrated relevant clinical activity in two Phase 2 clinical trials in heart failure, as well as in animal models of heart failure and nephropathy, among others. Alagebrium has been tested in approximately 1,000 patients in multiple Phase 1 and Phase 2 clinical trials, allowing Synvista Therapeutics to assemble a sizeable human safety database. For more information, please visit the Company’s website at http://www.synvista.com.

Any statements contained in this press release that relate to future plans, events or performance are forward-looking statements that involve risks and uncertainties including, but not limited to, the risks associated with the events described in this press release, future clinical development of Synvista Therapeutics’ product candidates, and other risks identified in Synvista Therapeutics’ filings with the Securities and Exchange Commission. Further information on risks faced by Synvista are detailed under the caption “Risk Factors” in Synvista Therapeutics’ Annual Report on Form 10-K for the year ended December 31, 2006. These filings are available on a website maintained by the Securities and Exchange Commission at http://www.sec.gov. The information contained in this press release is accurate as of the date indicated. Actual results, events or performance may differ materially. Synvista Therapeutics undertakes no obligation to publicly release the result of any revision to these forward-looking statements that may be made to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.

Synvista Therapeutics, Inc.
http://www.synvista.com

Artemisinins in Malaria Therapy, written by WRAIR researchers Dr. Qugui Li, Dr. Wilbur K. Milhous, and Dr. (COL) Peter J. Weina (Division of Experimental Therapeutics at the WRAIR, Silver Spring, MD) provides a fascinating overview of the historical use and recent developments in the treatment of one of the oldest and still one of the most prevalent scourges of mankind - malaria.

WRAIR, initially known as the Army Medical School, was founded in 1893 by then U.S. Army Surgeon General George Sternberg. In 1900 General Sternberg sent the newly appointed U.S. Army Yellow Fever Commission to Cuba headed by Major Walter Reed. Major Reed and his team became the first to confirm the theory that yellow fever was transmitted by a mosquito vector. Since this historic discovery, WRAIR’s many contributions to mankind in its 100 plus year history includes the discovery of the etiology and treatment of many of mankind’s leading killers.

More than half of the routine vaccines given to service members were co-developed by the military. Development of other licensed vaccines was supervised by investigators who began their careers at military research centers (e.g. yellow fever vaccine by former Army Surgeon General William Gorgas, mumps, measles, and varicella vaccines by Maurice Hilleman, and oral polio vaccine by Albert Sabin). Vaccines currently in advanced development stages include new adenovirus vaccines, and vaccines for malaria, dengue, and hepatitis E.

The history of using artemisinins for malarial like conditions dates back more than 2000 years to when it was a part of the herbal arsenal utilized in Traditional Chinese Medicine as a treatment for malarial like conditions. Artemisinins are derived from the sweet wormwood plant Artemisia annua which not only grows in China but also just down the road from WRAIR along the Potomac River. Revival of the use of artemisinins in the era of modern medicine began in China in the 1970’s with the first purified crystalline artemisinins produced in Shandon Province in 1972.

Although lead author Dr. Qigui Li received his MD and pharmacology degrees in China in the early 1980s, he did not become aware of artemisinins until the late 1980s, while a Post-doctoral Fellow at the Free University of Berlin, Germany. Dr. Li stated that “the Chinese had first published their findings in the Chinese Medical Journal in 1979, but when the WHO approached Chinese scientists for samples of the plant so they could conduct their own assays they were rebuffed. In retrospect, we can appreciate that this was just after the Nixon era, Mao Tse-tung was still in power, and the Chinese were very skeptical about sharing information for fear it would be utilized by the commercial pharmaceutical companies in the West for monetary gain.” Since joining the WRAIR team in 1991, Dr. Li has performed or supervised the majority of the pharmacodynamics and pharmacokinetics on all of the artemisinin derivatives.

In December of 2005, the World Health Organization stated, for the first time, artemisinins are the first line of therapy for most cases of malarial illnesses. Artemisinins are also being investigated as antiviral and anticancer agents.

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Dr. Dr. Qigui Li is currently the senior staff Pharmacologist and Section Chief of Pharmacokinetics/Pharmacodynamics in the Department of Pharmacology, Division of Experimental Therapeutics at the Walter Reed Army Institute of Research. He has received the WHO Research Fellowship Award, the NRC Research Associate Fellowship Award, and Best Investigator/PhD. Candidate from Schering Pharmaceuticals. Dr. Li received his Pharmacology/MD degree from Tongji Medical University, Wuhan, PR China in 1983 and his PhD in pharmacokinetics from the Free University of Berlin, West Berlin, FR Germany in 1989. Following the PhD in pharmacokinetics, Dr. Li completed a Postdoctoral Fellowship at the Free University of Berlin in 1991. He joined WRAIR in 1991.

Dr. Wilbur K. Milhous is currently a Professor of Global Health & Internal Medicine and serves as the Associate Dean for Research at the College of Public Health, University of South Florida (USF) in Tampa. He gained his 28 years of experience as a small molecule drug developer in numerous assignments at the WRAIR serving more recently as Chief Science Officer for Therapeutics and the Research Coordinator for the MIDRP. Under the mentorship of former WRAIR scientists Bob Desjardins and Craig Canfield, Dr. Milhous underwent his infectious disease chemotherapy training in a combined doctoral (University of North Carolina) and training with industry (GlaxoSmithKline) program prior to arriving at WRAIR in 1983. He was the first scientist to conduct in vitro testing of artemisinin extracts and has since been totally fascinated with the molecule resulting in numerous publications and patents. Dr. Milhous, along with former WRAIR colleague, Dennis Kyle, is currently teaching Critical Path Method as an academic discipline in the Global Health Infectious Diseases Research Program at USF Health.

Dr. (COL) Peter J. Weina is currently Chief, Pharmacology, , and Medical/Laboratory Director, Leishmaniasis Diagnostics Laboratory with the Division of Experimental Therapeutics at the Walter Reed Army Institute of Research, Silver Spring, MD. He is also Chair, Integrated Product Team for the Development of Intravenous Artesunate, Military Infectious Diseases Research Program and Medical Research and Material Command, Fort Detrick, MD. He received a PhD (Zoology & Pathology) from the University of Wisconsin-Madison in 1988 and completed his MD degree from the Uniformed Services University of Health Sciences in 1996. He completed a residency in Internal Medicine in 1999 and a Fellowship in Infectious Disease in 2002. Dr. Weina is currently a Fellow with the American College of Physicians and has been awarded one of America’s Top Physicians - Infectious Diseases (2004-2005).

When faced with cancer, the immune system dispatches cells, called T cells, to kill the tumor. But these killer cells often fail to completely eliminate the tumor because they’re deactivated by a distinct population of T cells known as regulatory T cells. Past attempts to get rid of these regulatory T cells have largely failed, in part because they share many features with the killer T cells, making it difficult to eliminate one population without also eliminating the other.

In the new study, the researchers focused on a cell-surface protein called OX40 that had previously been shown (in culture dishes) to turn off the regulatory T cells, but turn on the killer T cells. When this protein was activated in mice, the new study shows, the animals eliminated existing tumors and were protected against developing new ones.

The potential drawback of this approach is that selective inhibition of regulatory T cells could provoke naturally self-reactive T cells to attack the body’s own tissues (autoimmunity). The mice in the study, however, showed no signs of autoimmune disease, suggesting that OX40 may be a promising target for anti-cancer therapy.

Source: Hema Bashyam
Journal of Experimental Medicine

The discovery of the ubiquitous nature and influence of the human immune system on health and disease has led to the emergence of a number of powerful drugs that are bringing relief to patients afflicted with heretofore intractable conditions. These drugs include Enbrel, Remicade, and Humira for the treatment of inflammatory autoimmune diseases, Herceptin for oncology, and Avonex and Betaseron for multiple sclerosis. Each of these drugs had more than US $1 billion in sales in 2007. The ability of these and other drugs based on immune medicine to reap significant success in both human and commercial terms is fueling an accelerating level of interest in immune factor drugs for a growing list of ailments.

Therapeutic drug candidates based on immune factors currently in development include a diverse range of cytokines, immune cascade elements, and regulatory factors. These potential future drugs are targeting a spectrum of chronic and/or progressive indications that individually and as a group represent an enormous level of patient morbidity, mortality and diminished quality-of-life. In addition to a growing list of autoimmune and oncology indications, targeted therapeutic applications for pipeline immune factor drug candidates include infectious diseases, hereditary conditions, and metabolic diseases. More than three dozen pharmaceutical and biotechnology companies are now active in this sector.

The value of Immune factor drugs worldwide exceeded US $18 billion in 2007. Based on our projections of approved and likely-to-be-commercialized drugs, we expect the value of drugs in this sector to double by 2011.

These findings are contained in a new and comprehensive report: Immune Factor Drugs: Targets, Receptors and Therapeutics. The report analyzes fourteen approved and development-stage therapeutic immune factor drug segments representing sixty individual drugs and pipeline candidates, and examines their probably commercial impact on a dozen important chronic diseases.

About Greystone

Greystone Associates is a medical and healthcare technology consulting firm providing services in strategic planning, venture development, product commercialization, and technology and market assessment.

Greystone Associates

A team of Washington State University scientists has devised a method that could lead to the development of vaccines against some of the most troubling infectious diseases we face diseases that have so far been difficult or impossible to vaccinate against.

The new method allows researchers to rapidly screen large numbers of pathogen proteins, called antigens, for their ability to prompt an immune response in a host. Proteins with that ability are good candidates for use in vaccines. The method will be especially valuable in the quest for vaccines against persistent diseases such as malaria, sleeping sickness and syphilis.

“It’s very slick,” said immunologist Wendy Brown, who led the research effort. “Now we have a high-throughput way of finding antigens from any pathogen, as long as you have the genome sequence. To me this was a huge breakthrough, because I’ve been spending my whole career trying to figure out ways to do this.”

The research team included scientists at WSU and at the Rocky Mountain Laboratories of the National Institutes of Health.

A vaccine works by showing the body’s immune system a pathogen or part of a pathogen (usually a protein) so that it can develop cellular memory and antibodies that will recognize and attack the pathogen in the future. A key step in the development of a vaccine is identifying which protein(s) to use. Until now, screening pathogen proteins to find those few that might be good candidates has been laborious, time-consuming, and in the case of persistent diseases, not very successful. Brown said prior methods required about three months to produce and purify a single protein to test. With her new method she is able to screen dozens of proteins within a few weeks.

Brown’s group worked with Anaplasma, a bacterium that causes severe anemia in cattle. Anaplasma is the most common tick-borne pathogen of cattle worldwide and costs an estimated $100 million per year in lost animals and lowered productivity in the United States alone.

The new method starts with the pathogen’s DNA. Previous work by WSU scientists had determined the whole genome sequence of Anaplasma. By comparing that sequence with the genome sequences of better-known microbes, Brown’s team was able to pinpoint genes that code for proteins that stick out of the pathogen’s cell membrane. Brown reasoned that since those proteins are exposed on the surface of the cell, they should be visible to antibodies and immune system cells, and therefore could be a good way to target the pathogen.

Once the genes were isolated, Brown’s team made the proteins they coded for by using chemical ‘machinery’ derived from E. coli bacteria. They then purified each protein to get rid of any E. coli proteins that were present. They did that by using a chemical that would specifically bind to the Anaplasma proteins. Brown attached the chemical to tiny synthetic beads and then poured the protein mixture over the beads. Anaplasma proteins stuck to the beads, while E. coli proteins did not and were discarded. This purification step represented a big advance over other methods, which have been plagued by contamination with irrelevant proteins.

Each purified test protein was then presented to T cells from cows that had previously been exposed to Anaplasma outer membrane proteins. T cells are the immune system’s “memory cells.” In the body, when they recognize an antigen they have seen before, they trigger antibody production by other immune system cells. In Brown’s test, if the T cells recognized a protein, they started dividing and making interferon.

Using the new procedure, Brown’s team found T cells responded to about 20 proteins, including many that had never before been shown to stimulate a T cell response. The researchers are now testing whether any of these might form the basis for an effective vaccine against Anaplasma.

Brown said the new technique also will be a boon to researchers working on vaccines against pathogens that are highly contagious or especially deadly, such as the Ebola virus and the bacterium that causes anthrax. She is using it to screen proteins from Coxiella, a bacterium that causes Q fever and is considered a possible bioterrorism threat.

“If you have the genome, you don’t have to touch the organism. You can just start expressing all these proteins and test them,” Brown said.

Washington State University
PO Box 1040
Pullman, WA 99164-1040
United States
http://www.wsu.edu

Hugh Davis

Why are there not enough Quality Assurance Specialists for the on the market and why is it important to train the new specialists out of other professions with the right educational background?

In fact, the market is currently expanding faster than the production of new qualified professionals which inevitably creates a demand. Most people are under the impression that the barriers to enter this industry are extremely difficult to overcome, but the truth is that everybody working in this industry had to start somewhere and as the industry grows positions need to be filled. Now the question is: how will this be accomplished? One way of filling the vacuum is to take specialists from other professions and turn them into professionals for this industry. This has several added benefits of its own. For instance bringing specialists from other professions or industries actually diversifies the workforce and brings new perspectives to the biopharmaceutical industry. This in turn is a source of innovation where multiple disciplines are being united and new perspectives are made more apparent.

Of course, the need for training is obvious for specialists that are re-aligning their careers as well as for individuals that are entering the industry as new graduates. Most of the skills and knowledge required in positions such as Clinical Research Associates (CRA’s), Clinical Data Managers (CDM’s), Quality Assurance Specialists (QA) and Marketing Managers are not covered in university courses. Even where an individual has been through a specially designed training program for the position through an academic institution, the training may not involve a practical component in which case the individual still lacks certain skills. This should re-emphasize the importance of practical training programs for the biopharmaceutical industry.

he educational system does not appear to produce enough graduates to meet the demand for entry level positions like CRA, Data Manager Specialists, Quality Assurance Specialists and Marketing and Management specialists. Skill shortages also affect the ability of regulatory agencies to keep abreast of scientific advances and to efficiently review the increasing number of new products. The diverse range of skills required along with the dramatic pace of change is not reflected in current university courses. The shortage of specialists could be felt in other areas too. For example, bioinformatics requires a background in genetics, statistics, and software development, but most graduates lack such multi-disciplinary training. Also, there are not many undergraduate degree programs in QA in biotech; specialization options are normally offered within more traditional programs.

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Hugh Davis is a Senior Instructor , Kriger BioPharmaceutical Training Program http://www.kriger.com/training/ , info@kriger.com

Ardea Biosciences, Inc. (Nasdaq: RDEA) announced that data will be presented on its second generation non-nucleoside reverse transcriptase inhibitors (NNRTIs), at the 21st International Conference on Antiviral Research (ICAR). Additionally, data on two of the Company’s mitogen-activated ERK kinase (MEK) inhibitors, RDEA119 and RDEA436, will be presented at the American Association for Cancer Research (AACR) annual meeting.

The presentation details are as follows:

– 21st ICAR in Montreal, Quebec, Canada

Date/Time: Monday, April 14, 2008 at 4:00 p.m. Eastern Time
Title: A Novel NNRTI Class with Potent Anti-HIV Activity against
NNRTI-Resistant Viruses

Location: Poster Session 1 (Poster #80)

- AACR Annual Meeting in San Diego, California

Date/Time: Tuesday, April 15, 2008 at 1:00 p.m. Pacific Time
Title: RDEA119, a Potent and Highly Specific MEK Inhibitor is
Efficacious in Mouse Tumor Xenograft Studies
Location: Poster Session 32 (Poster #4878), Exhibit Hall B-F

Date/Time: Tuesday, April 15, 2008 at 1:00 p.m. Pacific Time
Title: RDEA436, a Novel MEK Inhibitor with Favorable
Pharmacokinetic Properties
Location: Poster Session 32 (Poster #4895), Exhibit Hall B-F

Studies published in the Jan. 10 edition of the New England Journal of Medicine (NEJM) are providing clues into the treatment and diagnosis of LAM, or lymphangioleiomyomatosis, a progressive and deadly lung disease that affects women in their childbearing years. There currently are no treatments for LAM and scientists estimate as many as 250,000 women may be going misdiagnosed or undiagnosed.

Researchers from Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine reported on a study testing the drug sirolimus in patients with LAM or tuberous sclerosis complex (TSC) with angiomyolipomas, benign kidney tumors common to both diseases. Approved to help transplant patients fight organ rejection, sirolimus treatment resulted in a 50 percent reduction in tumor growth; a significant improvement in lung function was observed in LAM patients. In addition, a letter published in the same issue of NEJM reports on preliminary data to support the use of a serum marker test to confirm a diagnosis of LAM. The disease has traditionally required a lung biopsy or CT scan for confirmation of diagnosis, contributing to diagnosis complications.

“These studies represent significant advances for LAM patients,” said Leslie Sullivan-Stacey, J.D., President and CEO of The LAM Foundation, a supporter of both studies. “The LAM Foundation has been the driving force behind major breakthroughs in LAM research over just the last decade, and we now have scientific evidence to support further study of treatments and diagnostic tools. The sirolimus study already is serving as the basis for other studies in TSC and LAM, including the first-ever LAM treatment trial, now enrolling patients.”

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