GMOs And Allergies: Tests May Help Answer Questions

The potential of genetically engineered foods to cause allergic reactions in humans is a big reason for opposition to such crops. Although protocols are in place to ask questions about the allergy-causing possibilities, there has been no test that offers definitive answers.

But all of that could change as a Michigan State University researcher has developed the first animal model to test whether genetically engineered foods could cause human allergic reactions. Venu Gangur, MSU assistant professor of food science and human nutrition, has received a $447,000 grant from the Environmental Protection Agency to validate the test.

Genetically engineered crops are created by inserting a protein from a different organism into the original crop’s genome. This is usually done to create a plant that is more resistant to insects or diseases.

The Food and Agriculture Organization within the World Health Organization has a structured approach to determining whether genetically engineered foods cause allergies, according to Gangur, who also is a faculty member in the National Food Safety and Toxicology Center. “But it has a major flaw. A critical question in that process asks, ‘Does the protein cause an allergic reaction in animals?’ The problem is that there has been no good animal model available to test this.”

Gangur and students in his lab have developed a mouse model – the first of its kind – to test the allergy-causing potential of genetically engineered foods. He’ll use the EPA grant to examine whether the model works on a variety of proteins. If successfully validated, the testing could be available commercially in about five years.

Perhaps the best known case of a genetically engineered crop potentially causing allergies was StarLink corn. Created by Aventis in 1996, StarLink contained the cry9C protein from a common soil bacterium, a strain of Bacillus thuringiensis. The cry9C protein protected the corn from several types of corn borers and black cutworms. StarLink was approved by the EPA for use in animal feed and nonfood products in 1998. But in 2000, fragments of cry9C DNA were detected in taco shells and other food products.

“Many people believed that StarLink was responsible for their asthma attacks and other allergic reactions,” Gangur said. “The Centers for Disease Control took samples and tried to figure out if StarLink was the cause, but the data were inconclusive. There was really no good method to determine if StarLink caused allergic reactions. This is why our model will be such a valuable tool. We’ll be able to determine the allergenic potential of genetically engineered crops before they’re released into the human or animal food chain.”

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Robert Tempelman, MSU professor of animal science and statistics and probability, is the project’s co-investigator.

Gale Strasburg, chairperson of the MSU Department of Food Science and Human Nutrition; and Jim Pestka and Maurice Bennink, MSU professors of food science and human nutrition, also are participating in the project.

The research of Gangur, Tempelman, Pestka and Bennink is supported by the Michigan Agricultural Experiment Station.

url: http://newsroom.msu.edu/site/indexer/2864/content.htm

Contact: Sue Nichols
American Society for Biochemistry and Molecular Biology

Vitamin A Analog Is A Potential Lung Cancer Preventative With Few Side Effects

The ideal substance to prevent cancer would block tumor growth without causing unpleasant or dangerous side effects. Researchers at Washington University School of Medicine in St. Louis now report that a compound related to vitamin A shows promise in preventing or slowing tumor growth in mice prone to lung cancer. The compound, called bexarotene, doesn’t cause the severe skin irritations that have limited the use of other vitamin A derivatives in cancer therapies.

“In the cancer prevention field, you look for drugs that can be given to healthy patients who have a higher risk of developing cancer,” says Ming You, M.D., Ph.D., director of the Chemoprevention Program at the Siteman Cancer Center. “These patients wouldn’t want to take a medication that makes them feel sick when they don’t have cancer. So the drugs should be very well-tolerated and not cause harmful side effects.”

In other studies, bexarotene showed some promise in cancer treatment. It extended survival in patients with non-small cell lung cancer, the most common type of lung cancer and one that has a five-year survival rate of less than 5 percent when diagnosed at the advanced stage.

In the current study, due to appear in an upcoming issue of Oncogene, Yian Wang, M.D., Ph.D., associate professor of surgery, You, professor of surgery, and colleagues demonstrate that lung-cancer-susceptible mice receiving non-toxic doses of bexarotene ended up with fewer and smaller benign and malignant tumors than mice that were not treated with bexarotene. The researchers saw a reduction of almost 50 percent in terms of total tumor burden in mice who were given bexarotene for 12 weeks after the animals had already developed benign tumors following injection of a lung carcinogen. Bexarotene also inhibited the progression of benign to malignant tumors by about 50 percent. The mice were engineered to have the genetic alterations seen in human lung cancers, so they readily develop lung cancer when given known lung carcinogens.

“Seeing this magnitude of response in such a strongly susceptible mouse suggests bexarotene is a potentially viable lung cancer prevention candidate,” You says.

Vitamin A analogs called retinoids have been studied for several years as potential chemotherapeutic agents because they help regulate cell division, growth, differentiation and proliferation. A new class of these vitamin A relatives has been created that includes bexarotene. These substances are called the rexinoids, so named because they are attracted to a molecule on cell surfaces called RXR.

Rexinoids tend to be much less toxic than retinoids, and among them bexarotene has so far shown the most promise as a chemopreventive medicine. However, although it causes far fewer side effects, bexarotene does have the effect of increasing blood lipid levels in many patients. Patients taking bexarotene often need to take a drug to lower their cholesterol and triglyceride levels.

A new rexinoid called UAB30, just becoming available for laboratory studies, seems to have the potential to reduce even the high-lipid side effect.

“We will be testing this new compound, too, and if it turns out to be effective, these rexinoids will most likely become candidates for clinical trials in patients with precancerous nodules or bronchial dysplasia,” You says. “If the trials show reduction of cancers, I think these drugs may well become routinely used for lung cancer prevention.” Prevention is considered vital to decreasing the impact of lung cancer, which accounts for 32 percent of cancer deaths in men and 25 percent of cancer deaths in women. The majority of lung cancer patients are not diagnosed until their cancer has reached an advanced stage, and current treatment regimens do not substantially improve the outcome for most of these patients.

“Advanced or metastatic cancer is sort of a genius at adapting,” You says. “By that point, the cancer cells that have survived have overcome so many obstacles and gained so many abilities that they are difficult to kill. They have a very unstable genome that can change quickly to resist the treatments we use. It’s best if you attack cancer in its infancy or at the precancerous stage. The earlier the better.”

Wang Y, Zhang Z, Yao R, Jia D, Wang D, Lubet RA, You M. Prevention of lung cancer progression by bexarotene in mouse models. Oncogene 2006.

Funding from the National Institutes of Health supported this research.

Washington University School of Medicine’s full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Siteman Cancer Center is the only NCI-designated Comprehensive Cancer Center within a 200-mile radius of St. Louis. Siteman Cancer Center is composed of the combined cancer research and treatment programs of Barnes-Jewish Hospital and Washington University School of Medicine.

Gwen Ericson
ericsong@wustl.edu
Washington University School of Medicine
http://medinfo.wustl.edu

A Call To Action For People With Diabetes: Take Steps To Lower Your Risk For Heart Disease

People with diabetes must closely manage their blood glucose, blood pressure and cholesterol levels, or face a significantly increased risk of cardiovascular disease, say three leading health organizations. Research has shown that two out of three people with diabetes die from a heart attack or stroke, making cardiovascular disease the number one killer of people with diabetes. The American Diabetes Association (ADA), the American College of Cardiology (ACC) and the National Diabetes Education Program (NDEP) are collaborating during November — American Diabetes Month — to emphasize the critical link between diabetes and related cardiovascular complications.

In particular, tight control of blood glucose can significantly reduce the likelihood of a heart attack or stroke in people with diabetes, according to data from a study commissioned by the National Institutes of Health (NIH). The Epidemiology of Diabetes Interventions and Complications (EDIC) study was a follow-up to NIH’s Diabetes Control and Complications Trial (DCCT) on people with type 1 diabetes, conducted from 1983 to 1989. Results from the EDIC study showed that intensive control of blood glucose in patients with diabetes reduced the risk of heart attacks and stroke by more than 50 percent. Experts agree that this finding adds to a strong and growing body of evidence that everyone with diabetes — whether it is type 1 or type 2 diabetes — gains from blood glucose control.

Unfortunately, data from the Centers for Disease Control and Prevention (CDC) suggest that fewer than 50 percent of Americans with diabetes are reaching the level of glucose control recommended by the ADA, which is an A1C level of less than seven percent. This alarming trend contributes to the disproportionate number of people with diabetes who experience cardiovascular events, such as a heart attack or stroke.

“For most people with diabetes, keeping blood glucose under tight control isn’t easy — but the benefits of control are indisputable,” said John Buse, MD, PhD, President-Elect, Medicine & Science, of the American Diabetes Association. “Controlling blood glucose, along with blood pressure and cholesterol, can help save not only a person’s heart, eyesight and limbs, but a person’s life. It’s what we call the ABCs of diabetes.”

In addition to tight blood glucose control, people with diabetes need to manage other risk factors for cardiovascular disease, such as blood pressure and cholesterol levels. In fact, it is estimated that approximately 73 percent of adults with diabetes have high blood pressure and most have cholesterol levels that put them at increased risk for cardiovascular disease.

“It is clear that we all need to work harder to help people with diabetes manage their ABCs,” said Griffin P. Rodgers, M.D., M.A.C.P., Acting Director of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. “The truly amazing news from the EDIC study is that more than a decade after they left the DCCT and returned to the care of their own doctors, participants are still benefiting from the relatively brief period of intense blood glucose control they had during the study, and they continue to have significantly lower risks for cardiovascular disease, as well as retinopathy, nephropathy, and neuropathy.”

Together, ADA, ACC and NDEP are urging patients to talk with their health care providers about managing the “ABCs of Diabetes.” For most people with diabetes the goals are:

— A1C (measures average blood glucose over the past 2 to 3 months): less than 7 percent. Check at least twice a year.

— Blood pressure: below 130/80. Check at every doctor’s visit.

— Cholesterol (LDL): below 100. Check at least once a year.

The groups offer the following advice to help manage blood glucose, blood pressure, and cholesterol: make wise food choices, engage in daily physical activity and take prescribed medications. People with diabetes should also avoid smoking and consult their health providers about taking aspirin.

ADA and ACC have developed a diabetes survival guide called “Choose to Live” to give people with diabetes information they need to help reduce diabetes-related complications such as heart disease and stroke. Contact the ADA at 1-800-DIABETES or visit http://www.diabetes.org for a free copy. NDEP promotes its Control Your Diabetes. For Life. campaign, which offers materials with ideas for sticking to a healthy eating plan, ways to stay active with regular physical activity, and other tips for feeling better and staying healthy. Contact NDEP at http://www.ndep.nih.gov or at 1-800-438-5383. Educational materials are available in English, Spanish and 15 Asian and Pacific Islander languages.

The American Diabetes Association is the nation’s leading voluntary health organization supporting diabetes research, information and advocacy. Founded in 1940, the Association has offices in every region of the country, providing services to hundreds of communities.

The American College of Cardiology, a 34,000-member nonprofit professional medical society and teaching institution, is the leading organization dedicated to advocating for quality cardiovascular care.

The National Diabetes Education Program, the leading federal government source of information about diabetes prevention and control, is sponsored by the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC) and 200 public and private partners.

American Diabetes Association
http://www.diabetes.org

Flu Vaccine Recommended For People With Asthma

With flu season just around the corner, the American Academy of Allergy, Asthma & Immunology (AAAAI) is recommending that people with asthma and other chronic health conditions receive a flu vaccination as soon as possible.

Each year, millions of people in the United States get influenza. According to the Centers for Disease Control and Prevention (CDC), approximately 36,000 people per year in the United States die from influenza, and over 200,000 people have to be admitted to the hospital as a result of the flu.

Influenza is typically spread from person to person through coughing and sneezing via respiratory droplets. If someone with the flu coughs on you, there is a high chance you will develop flu symptoms within four days after the initial exposure to that person. Common flu symptoms include:

— Fever
— Muscle aches and tenderness
— Headache
— Fatigue
— Dry cough
— Sore throat
— Runny nose

“Symptoms of influenza can be especially severe for patients with respiratory diseases, such as asthma,” said Richard A. Nicklas, MD, FAAAAI, Chair of the AAAAI’s Asthma Diagnosis and Treatment Interest Section. “In severe cases, influenza can cause pneumonia, may require hospitalization and sometimes can be fatal.

” Research has found that the flu vaccine decreases the risk of asthma exacerbations in patients by as much as 22% to 41%. In addition, it can also protect against acute asthma exacerbations in children. Vaccinating all children with asthma could prevent up to 78% of asthma hospitalizations and emergency room visits during influenza seasons.

The flu season usually ranges from November through March, and peaks in December, January and February. It takes approximately two weeks to develop immunity from the vaccine so it is important to get vaccinated each fall in October or November, before the flu season begins.

Contrary to popular belief, you cannot get the flu from the flu vaccine. If you feel sick with flu-like symptoms after being vaccinated, you may have caught another respiratory virus or already had the flu virus in your system when you received the vaccine.

Discuss any questions that you may have regarding influenza or the flu vaccine with your physician. For more information, visit the AAAAI Web site, http://www.aaaai.org, the Centers for Disease Control and Prevention (CDC) Web site, http://www.cdc.gov/nip/flu, or call the CDC Immunization Hot Line at (800) 232-2522.

The AAAAI’s How the Allergist/Immunologist Can Help: Consultation and Referral Guidelines Citing the Evidence provide information to assist patients and health care professionals in determining when a patient may need consultation or ongoing specialty care by the allergist/immunologist. Patients should see an allergist/immunologist if they:

— Need to confirm the diagnosis of asthma
— Need education on asthma and guidance in techniques for self-management.
— Need for daily asthma reliever medications
— Are not using medications as prescribed, and this is limiting their ability to control their asthma
— Have potentially fatal asthma, meaning a prior severe, life threatening episode that included intubation

To find an allergist/immunologist in your area, call the AAAAI Physician Referral and Information Line at (800) 822-2762 or visit the AAAAI Web site at http://www.aaaai.org/physref/.

The AAAAI is the largest professional medical specialty organization in the United States representing allergists, asthma specialists, clinical immunologists, allied health professionals and others with a special interest in the research and treatment of allergic disease. Established in 1943, the AAAAI has more than 6,000 members in the United States, Canada and 60 other countries. The AAAAI serves as an advocate to the public by providing educational information through its Web site at http://www.aaaai.org.

American Academy of Allergy, Asthma & Immunology (AAAAI)
http://www.aaaai.org

Scientists Find Unusual Lung-cancer Tumor-suppressor Gene

Researchers have identified a new and unusual tumor suppressor gene that may be important in cancers of the lung and head and neck. The study shows that restoring the inactivated gene can slow the growth of tumor cells.

The gene, known as TCF21, is silenced in tumor cells through a chemical change known as DNA methylation, a process that is potentially reversible.

The findings might therefore lead to new strategies for the treatment and early detection of lung cancer, a disease that killed an estimated 163,510 Americans in 2005. The study could also lead to a better understanding of the molecular changes that occur in tumor cells during lung-cancer progression.

Tumor-suppressor genes are genes that normally prevent cells from growing out of control. The loss or silencing of one or more tumor-suppressor genes is believed to be an important part of cancer development.

The study, by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, was published online in the Jan. 13 early edition of the Proceedings of the National Academy of Sciences.

The newly discovered gene is unusual because it can alter normal epithelial cells, causing them to change to a more primitive state. Epithelial cells form the skin and line the body’s passageways and hollow organs. They are also the source of the most common forms of cancer.

The more primitive cell type, known as a mesenchymal cell, is more commonly found in embryos and is capable of migrating to other tissues. This suggests that the silencing of the TCF21 gene might help a tumor to spread to other areas of the body, a process known as metastasis.

The gene is also often silenced or lost in a variety of other cancers, including breast and ovarian cancer, melanoma and lymphoma.

“The fact that this gene is silenced in many cancer types strongly suggests that it plays an important role in cancer development,” says principal investigator Christoph Plass, a professor of molecular virology, immunology and medical genetics and a researcher in the OSU Human Cancer Genetics Program.

In addition, says first author Laura T. Smith, a postdoctoral fellow in Plass’ laboratory, “because this gene is silenced by DNA methylation, it might be possible to reactivate it using drugs that reverse the methylation process. This could provide a new strategy for treating these cancers.”

The gene is found on chromosome 6 in a region known as 6q23-24, an area that contains hundreds of genes. Other researchers have searched this region looking for mutations that might lead them to a silenced tumor-suppressor gene, but, Plass says, “that strategy has been unsuccessful.”

DNA methylation, which is a chemical change and not a mutation, is another way that genes are silenced. For this study, Plass and his colleagues systematically scanned the same chromosome region using a technology known as restriction landmark genome scanning, which identifies methylated genes.

The researchers examined the region in about 50 tumor samples from patients with head and neck squamous-cell carcinomas and with non-small-cell lung cancer, which is responsible for about 85 percent of lung cancer cases. From this, they identified TCF21 as a gene often silenced by methylation compared with normal airway cells.

“A picture is emerging that certain genes tend to be silenced mainly by DNA methylation, while others tend to be silenced by genetic mutations,” Plass says. “This gene seems to be silenced by DNA methylation.”

Through a series of experiments, Plass and his colleagues showed that an active TCF21 gene can, in fact, be silenced by DNA methylation, and that drugs that reverse methylation can reactive it.

The researchers also used a lung-cancer cell line to show that if the active version of the TCF21 gene is placed in tumor cells, the active gene will slow the cells’ growth rate.

Lastly, the researchers showed that mice injected with lung-tumor cells that had an active TCF21 gene developed tumors that were two to three times smaller than tumors that developed from cancer cells with a silent TCF21 gene.

Plass and his colleagues are now studying the possible role of TCF21 in metastasis.

Funding from the National Cancer Institute and the National Institute of Dental and Craniofacial Research supported this research.

Darrell E. Ward
Darrell.Ward@osumc.edu
Ohio State University
http://researchnews.osu.edu

Akesis Pharmaceuticals Manufactures Drug Product For Clinical Trials In Type 2 Diabetes

Akesis Pharmaceuticals, Inc. (OTC Bulletin Board: AKES.OB) today announced that it has completed manufacturing of several lots of its proprietary combination drug candidate AKP-101 through its manufacturing partner, Douglas Laboratories of Pittsburgh, PA, to support the initiation of new clinical trials in type 2 diabetes. Akesis is designing a double-blind placebo controlled trial to evaluate the effectiveness of AKP-101, in combination with metformin, in lowering and controlling blood glucose levels in type 2 diabetes patients.

Akesis holds numerous issued patents and patent applications relating to the use of chromium, vanadium and other components with metformin, sulfonylureas, and other classes of diabetic agents. In an open-label study, Akesis demonstrated significant reductions in glycated hemoglobin (HbA1c) levels in subjects with type 2 diabetes when administering one of its products in combination with metformin and sulfonylureas.

“This achievement represents an important step toward our goal of bringing to market improved therapies for individuals with type 2 diabetes,” said Akesis president and CEO Jay Lichter, Ph.D. “Our manufactured drug product was made under cGMP guidelines and is suitable for our upcoming trial.”

About Akesis:

Akesis is a pharmaceutical company with a portfolio of innovative prospective treatments for diabetes and other related metabolic disorders. The company possesses issued U.S. patents for both prescription and over-the- counter treatments, which uniquely combine anti-diabetic trace minerals with certain classes of diabetes oral agents. Akesis’ products have demonstrated utility in lowering and controlling blood glucose levels in patients with type 2 diabetes. Blood sugar control via oral drugs represents a multi billion- dollar industry in the United States.

Note regarding forward-looking statements:

This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Akesis Pharmaceuticals disclaims any intent or obligation to update these forward- looking statements, and claims the protection of the Safe Harbor for forward- looking statements contained in the Act. Examples of such statements include, but are not limited to, any plans to initiate clinical trials or to otherwise seek to confirm the utility of the company’s products, and the suitability of these products for clinical trials. Such statements are based on management’s current expectations, but actual results may differ materially due to various factors. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to the inability to raise additional capital, an amount of which is required to support completion of new clinical trials, difficulties or delays in development, testing, regulatory approval, production and marketing of the company’s drug candidates, unexpected adverse side effects or inadequate therapeutic efficacy of the company’s drug candidates that could slow or prevent clinical development, and product approval or market acceptance (including the risk that current and past results of clinical trials are not necessarily indicative of future results of clinical trials). For additional information about risks and uncertainties Akesis faces, see documents Akesis files with the Securities and Exchange Commission, including the report on Form 10-K for the fiscal year ended December 31, 2005, and all our quarterly and other periodic SEC filings. Akesis has not yet submitted any formulations to the Food and Drug Administration for review. The FDA has not made any determinations with regard to Akesis’ proposed formulations. Akesis does not, at this time, manufacture or offer products for sale.

Akesis Pharmaceuticals, Inc.
http://www.trubion.com/

New England Journal OF MEDICINE Reports Positive Results From Dynavax’ Ragweed Allergy Therapy Trial

The NEW ENGLAND JOURNAL OF MEDICINE (Vol. 355, October 5, 2006, No.14), today reported that a new approach to allergy therapy not only reduced the acute allergic responses of individuals with ragweed allergies but also sustained that effect for over 12 months. The novel treatment, called “AIC” in the paper, is a TLR9 agonist linked to ragweed allergen, developed by Dynavax Technologies Corporation (Nasdaq: DVAX).

Dr. Peter Creticos, principal investigator and lead author of the paper, entitled, “Immunotherapy with a Ragweed-Toll-like Receptor 9 Agonist Vaccine for Allergic Rhinitis,” said that the pilot study “appears to offer a means of achieving long-term clinical efficacy in ragweed allergic rhinitis as the clinical effects suggest the induction of long-lasting disease modification. Furthermore, the demonstrated therapeutic properties and safety pave the way for a therapeutic intervention that is qualitatively superior to standard immunotherapy.” Dr. Creticos is Associate Professor of Medicine and Clinical Director of the Division of Clinical Immunology of The Johns Hopkins University School of Medicine. He serves as Medical Director of the Johns Hopkins Asthma and Allergy Center in Baltimore, Maryland.

In the paper, Dr. Creticos pointed to statistically significant efficacy results including peak Nasal Symptom Complex Score (NSCS) reductions in AIC-treated patients of 55% (p=0.03) in 2001 which persisted through the 2002 ragweed season (53% reduction in NSCS, p=0.02) with no additional therapy. Additionally, the AIC-treated group used no relief medication at all during the second season, while placebo patients used antihistamines for 8 days (average) and decongestants for 4 days (average) of the two-week peak season. The intervention also generated clinically significant quality of life improvements for patients. Dr. Creticos added that the intervention was safely tolerated as no treatment-associated serious adverse reactions were reported, nor did any lab tests show abnormalities in the patients tested.

With funding from the National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network, and the study drug provided by Dynavax, Dr. Creticos conducted a blinded, randomized, placebo-controlled, clinical trial in 25 ragweed allergic patients beginning in May 2001 and concluding in October, 2002. Patients were treated with either the drug or placebo, using a 6-injection regimen, prior to the first ragweed season, and were followed for two years. Dynavax supplied the study drug, now known as TOLAMBA(TM), and contributed to trial design, but did not participate in data accrual, analysis, or funding of the trial. TOLAMBA, consisting of a TLR9 agonist linked to a specific ragweed allergen, is currently being evaluated in late-stage clinical trials for the treatment of allergic rhinitis.

DYNAVAX Clinical Trials Update

In the paper, Dr. Creticos recommends additional large-scale studies, which are now underway at Dynavax. Since the reported study’s initiation in 2001, Dynavax has generated a substantial amount of data in 14 clinical trials in the U.S., France, and Canada. More than 7,000 TOLAMBA injections have been administered to over 1,100 patients. In these trials, TOLAMBA was shown to be safe and well tolerated, to provide measurable improvements in allergy symptoms, and to reduce medication use.

TOLAMBA consists of 1018 ISS, a TLR9 agonist, linked to the purified major allergen of ragweed, called Amb a 1. The linking of ISS to Amb a 1 ensures that both ISS and ragweed allergen are presented simultaneously to the same immune cells, producing a highly specific and potent effect suppressing the Th2 cells responsible for inflammation associated with ragweed allergy. Moreover, this treatment reprograms the immune response away from the Th2 response and toward a Th1 memory response so that, upon subsequent natural exposure to the ragweed allergen, long-term protection is achieved.

Other Clinical Results; Trial Background

A Dynavax-funded, 30-center, placebo-controlled study in 738 ragweed allergic subjects, aged 18 to 55 years, is expected to produce interim data at one-year in the first quarter of 2007. The study known as “DARTT” (Dynavax Allergic Rhinitis TOLAMBA Trial) randomized subjects into three arms: the same dosing regimen that was used in the completed Phase 2/3 trial; a higher total dose regimen; and placebo. Subjects received six doses over six weeks prior to the start of the 2006 ragweed season. Ragweed symptoms were followed over the 2006 ragweed season and will also be followed through the 2007 season. The primary endpoint is reduction in total nasal symptom scores (TNSS) during the second (2007) peak ragweed season. Dynavax anticipates that data from the DARTT interim analysis, if positive, combined with the safety and efficacy data from the recently completed two-year Phase 2/3 trial, and from an ongoing trial in ragweed allergic children, could provide sufficient patient data for determining the potential timeline to registration for the intervention.

Additionally, Dynavax is evaluating TOLAMBA in a three-year, 19-center, pediatric trial with over 300 patients, ages six to 15 years. The primary endpoint of the study is reduction in TNSS during the 2006 peak ragweed season; a key secondary endpoint is the prevention of progression to asthma. The study was initiated in early 2005. Primary endpoint data for the study is expected in early 2007.

In January 2006, Dynavax announced that results from a two-year Phase 2/3 clinical trial of TOLAMBA showed that patients treated with TOLAMBA experienced a statistically significant 28.5% reduction in total nasal symptom scores (TNSS) compared to placebo-treated patients in the second year of the trial (p=0.024). Results also showed significant clinical benefit relative to secondary endpoints, including composite hay fever symptoms and ocular effects, and a significant reduction in antihistamine use (p=0.01). These results were achieved after a single short course of therapy prior to the first ragweed season (2004), and demonstrated that a booster dose prior to the second season (2005) was not required to achieve clinical benefit. The safety profile of TOLAMBA was favorable; systemic side effects were indistinguishable from placebo and local injection site tenderness was minor and transient.

TOLAMBA represents the foundation of a comprehensive allergy franchise for Dynavax, and has the potential to be a novel entrant in the multibillion- dollar global allergy market. In the U.S. alone, approximately 40 million people suffer from allergic rhinitis. Ragweed is the single most common seasonal allergen, affecting up to 75% of those with allergic rhinitis, or 30 million Americans. Current therapeutic options are mainly limited to symptomatic therapies and conventional allergy immunotherapy, which generally requires 60-90 shots over three to five years and represents a significant treatment burden for allergy sufferers. Dynavax believes that TOLAMBA has the potential to become the first of several new and important disease-modifying therapeutic options for patients and physicians.

About Dynavax

Dynavax Technologies Corporation discovers, develops, and intends to commercialize innovative TLR9 agonist-based products to treat and prevent allergies, infectious diseases, cancer, and chronic inflammatory diseases using versatile, proprietary approaches that alter immune system responses in highly specific ways. Our clinical development programs are based on immunostimulatory sequences, or ISS, which are short DNA sequences that enhance the ability of the immune system to fight disease and control chronic inflammation. Dynavax’s pipeline includes: TOLAMBA, a ragweed allergy therapeutic, for which a major safety and efficacy trial (DARTT) is currently underway, and that is in a supportive clinical trial in ragweed allergic children; HEPLISAV(TM), a hepatitis B vaccine in Phase 3; and a therapy for non-Hodgkin’s lymphoma in Phase 2. Its preclinical asthma and COPD programs are partnered with AstraZeneca. Funding for the company’s other preclinical programs in cancer, hepatitis B and hepatitis C therapies, and for an influenza vaccine have been provided by Symphony Dynamo and NIH, and represent future partnering opportunities. Preliminary data from the study published today in the NEJM were previously reported at the AAAAI 2003 annual meeting. For more information, please visit http://www.dynavax.com.

This press release contains forward-looking statements that are subject to a number of risks and uncertainties, including statements about our clinical development plans and timelines, business plans, future operating results, intellectual property position and potential sources of funds. Actual results may differ materially from those set forth in this presentation due to the risks and uncertainties inherent in our business, including difficulties or delays in development, achieving the objectives of our collaborative and licensing agreements and obtaining regulatory approval for our products; the scope and validity of patent protection for our products; competition from other companies; our ability to obtain additional financing to support our operations; and other risks detailed in the “Risk Factors” section of our Annual Report on Form 10-K and Quarterly Report on Form 10-Q. We undertake no obligation to revise or update information herein to reflect events or circumstances in the future, even if new information becomes available.

Dynavax Technologies Corporation
http://www.dynavax.com

Palliative Radiation Actually A Cure For Some Lung Cancer Patients

About one in a hundred patients with apparently incurable non-small cell lung cancer (NSCLC) survive five or more years after being given relatively small doses of radiation therapy (RT) meant to ease symptoms, according to a new study. Published in the March 1, 2006 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the study says a new subset of patients with NSCLC appears to have disease that is curable with minimal therapy, and may explain occasional cures attributed to unconventional therapies or faith healing.

NSCLC is by far the most common type of lung cancer. With an overall five year survival of only 40 percent, it is also one of the deadliest. If caught early, five year survival can reach 60 percent. Five year survival in farther advanced disease is approximately 15 percent.

Patients who are diagnosed with disease that is too advanced for curative treatment remain eligible for palliative therapies intended to provide symptom relief, including comparatively low doses of localized RT. Physicians have long made clinical observations that some patients receiving palliative RT long outlive their estimated survival and a few report even cures. Given that therapeutic doses of RT are much higher, it is not surprising that these reports require evidence-based confirmation.

Michael Mac Manus, M.D., a radiation oncologist at the Peter MacCallum Cancer Centre in Melbourne, Australia, and colleagues clinically followed 2337 confirmed and apparently incurable NSCLC patients who had received palliative dose RT.

Approximately 1.1 percent of the 2337 survived five or more years, including 18 who achieved an apparent cure. Although five year survivors were more likely to have higher functional scores at diagnosis and less likely to have metastatic disease compared to patients who lived less than five years, there were no other conventional prognostic factors to predict survival with palliative-dosed RT.

“Our data,” conclude the researchers “show that close to 1 percent of patients with NSCLC have prolonged survival with doses of palliative RT that would not normally be considered sufficient for long term disease control.” Future studies should focus on identifying patient characteristics because “prospective identification of such patients could potentially profoundly influence treatment.”

Article: “Unexpected Long-Term Survival after Low-Dose Palliative Radiotherapy for Nonsmall Cell Lung Cancer,” Michael P. Mac Manus, Jane P. Matthews, Morikatsu Wada, Andrew Wirth, Valentina Worotniuk, CANCER; Published Online: January 23, 2006 (DOI: 10.1002/cncr.21704 ); Print Issue Date: March 1, 2006.

John Wiley & Sons, Inc.
http://www.interscience.wiley.com

Sugar-Control In Type II Diabetes May Be Improved With Herbal Medicine Silymarin

Diabetes is a growing health problem. Giving antioxidants is recognised as one way of helping people with diabetes to control their blood sugar levels.

The herbal medicine extracted from seeds of the Milk Thistle, Silybum marianum (silymarin) is known to have antioxidant properties and research published this week in Phytotherapy Research shows that this extract can help people significantly lower the amount of sugar bound to haemoglobin in blood, as well as reducing fasting blood sugar levels.

Silymarin contains a number of active constituents called flavolignans which are also used to help protect the liver from poisoning.

“We don’t know the exact mechanism of action for this effect, but this work shows that silymarin could play an important role in treating type II diabetes,” says lead author Fallah Huseini, who works at the Institute of Medicinal Plants, which is based in Tehran, Iran.

The data came from a randomized double-blind clinical trial involving 51 people who had had type II diabetes for at least 2 years. One group of 25 patients received 200 mg of silymarin three times a day for 4 months, while the remaining 26 received a placebo treatment. All of the patients continued to use conventional oral hypoglycaemic treatment during the trial. Patients were examined at monthly intervals.

Compared with the beginning of the trial, the treatment group had a significant reduction in fasting blood glucose levels (p
“The results are very encouraging, and we now need to do further large multi-centre studies,” says Huseini.

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Huseini, H.F: The Efficacy of Silybum marianum (L.) Gaertn. (Silymarin) in the Treatment of Type II Diabetes: A Randomized, Double-blind, Placebo-controlled, Clinical Trial

Phytotherapy Research is an international journal for the publication of original medicinal plant research, focussing on pharmacology, toxicology and the clinical applications of herbs and natural products in medicine. Papers concerned with the effects of common food ingredients and standardised plant extracts, including commercial products, and mechanistic studies on isolated natural products are particularly welcome. Papers and communications range from case studies to full clinical trials, including studies of herb-drug interactions and other aspects of the safety of herbal medicines. Phytotherapy Research can be accessed online at: http://www.interscience.wiley.com/journal/ptr

John Wiley & Sons Ltd., with its headquarters in Chichester, England, is the largest subsidiary of John Wiley & Sons, Inc. Founded in 1807, John Wiley & Sons, Inc., provides must-have content and services to customers worldwide. Its core businesses include scientific, technical, and medical journals, encyclopaedias, books, and online products and services; professional and consumer books and subscription services; and educational materials for undergraduate and graduate students and lifelong learners. Wiley has publishing, marketing, and distribution centres in the United States, Canada, Europe, Asia, and Australia. The company is listed on the New York Stock Exchange under the symbols JWa and JWb. Wiley’s Internet site can be accessed at http://www.wileyeurope.com/

Contact: Polly Young
John Wiley & Sons, Inc.

Ragweed Allergy Vaccine Effective For At Least One Year

A new vaccine trial has been shown to protect people from ragweed pollen allergy for at least one year, according to an article in the New England Journal of Medicine. This experimental treatment requires just six injections, once a week. Current treatments require taking several medications each day throughout the ragweed season.
Allergic reactions to plant pollens are commonly known as Hay Fever

Trial researchers said further studies have to be carried out on a larger group of volunteers.

Study author, Dr. Peter Socrates Creticos, Johns Hopkins Asthma and Allergy Center, Baltimore, USA, and team, expanded on studies that had been carried out at the University of California, San Diego, which discovered that a bacterium DNA sequence shuts down Th2 (T-helper) cell activity – an inflammatory immune system response. Th2 is commonly found to be a major factor in human allergic responses.

To create a new vaccine the team attached the DNA sequence that halts Th2 response to a portion of the ragweed pollen. Th2 cells often overreact to ragweed pollen – the new vaccine stops the Th2 from overreacting.

The Th2 cells of people who are allergic to ragweed make the body produce igE, which causes the watery eyes and sneezing. The vaccine stops the Th2 cells from sending signals which make the body produce IgE when exposed to ragweed.

The problem with current allergy medications is that they are not well targeted. Current medications have side effects because they undermine the body’s immune system. This new vaccine is finely targeted – there are fewer side effects, say the researchers.

Twenty-five volunteers, aged 23-60, took part in this pilot trial,. All of them suffered from ragweed allergy. 14 were given six injections with the new vaccine, one each week consecutively. The other 11 were given a placebo injection, once a week for six weeks. Both groups started treatment before the ragweed season began.

Allergy symptoms during the ragweed season were 60% lower for the 14 who received the new vaccine, compared to the placebo group. Allergy relief continued during the next season, a year later (no additional treatment had been given).

Ragweed Allergy – Some Facts

The ragweed pollen season runs from August to November. Most areas in the USA see a peak in ragweed pollen levels in mid-September. Pollen counts tend to peak between 5am to 10am.

If you suffer from ragweed pollen allergy

— Try to stay indoors between 5am to 10am – unless there has been some heavy rain
— Try to keep the windows of your home and car closed
— Avoid using fans
— If your allergy is severe, remember that people can bring the pollen into the home on their clothing
— Pets can bring the pollen in
— Avoid drying your clothes by hanging them outside

Symptoms

— eye irritation
— inflamed, itchy nose and throat
— puffy eyes
— runny nose
— sneezing
— stuffy nose
If your allergy is more severe, symptoms may also include the following:
— asthma attacks
— chronic sinusitis
— headaches
— impaired sleep

Immunotherapy with a Ragweed-Toll-Like Receptor 9 Agonist Vaccine for Allergic Rhinitis
Peter S. Creticos, M.D., John T. Schroeder, Ph.D., Robert G. Hamilton, Ph.D., Susan L. Balcer-Whaley, M.P.H., Arouna P. Khattignavong, M.D., Robert Lindblad, M.D., Henry Li, M.D., Ph.D., Robert Coffman, Ph.D., Vicki Seyfert, Ph.D., Joseph J. Eiden, M.D., Ph.D., David Broide, M.B., Ch.B., and the Immune Tolerance Network Group
NEJM Volume 355:1445-1455 – October 5, 2006 – Number 14
Click here to see abstract online

Written by: Christian Nordqvist
Editor: Medical News Today