The new research shows that a gene known as GATA-3 can block the development of regulatory T-cells in the immune system by locking another gene. This gene, FOXP3, is key to regulatory T cells and when it is blocked new regulatory T cells stop being produced.

The scientists, from Imperial College London, the Swiss Institute of Allergy and Asthma Research in Davos, Switzerland, and other international institutions, hope that if they can develop therapies to stop FOXP3 being blocked, they can ensure that regulatory T cells are free to work normally.

Regulatory T cells are believed to be vital for averting allergic reactions in healthy individuals because they keep the other cells in check, suppressing pro-allergic cells known as Th2 cells and stopping the immune system from needlessly attacking the body.

In people with allergies, some types of cells in the immune system, particularly the Th2 cells, wrongly identify a particular allergen, such as pollen, as being dangerous. Whenever the person encounters this allergen again, these cells promote the production of antibodies to attack it, causing an allergic reaction.

Dr Carsten Schmidt-Weber, the principal investigator on the research from the National Heart and Lung Institute at Imperial College London, said: “This finding will help us to understand how healthy individuals are able to tolerate allergens and what we need to do to re-induce tolerance in the immune systems of patients with allergies. We hope that we will soon be able to help not only patients suffering from single allergies, but also those with multiple ones – the atopic patients.”

The researchers reached their conclusions by analysing the genes related to regulatory T-cells and analysing how they interacted. They confirmed their findings by using mouse models to show that mice which were genetically engineered to express the GATA-3 gene in all T cells showed dramatic defects in the production of regulatory T-cells.

Dr Schmidt-Weber and his colleague Professor Stephen Durham, also from the National Heart and Lung Institute at Imperial College, hope the new findings will eventually lead to new, more effective treatments for hayfever and other allergies, to be used in combination with existing immunotherapies. They hope such treatments could help prevent hay fever and allergic asthma from reaching epidemic proportions.

This research was funded by the Swiss National Science Foundation, the Ehmann Foundation Chur, the Saurer Foundation Zurich and Swiss Life Zurich.

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“Over the past few years, the utilization of contrast-enhanced MRI has markedly increased; it’s increased by 65% at our institution over the previous five years,” said Dr. Dillman.. This is due, at least in part, to a variety of new applications, such as magnetic resonance angiography (MRA) and abdominopelvic MR imaging,” he said. “Consequently, the number of intravenously administered gadolinium-containing contrast material doses over the same time period has significantly increased. Based on the extensive use these intravascular contrast agents, we felt that it was once again time to study their safety profile,” he said.

The study included 78,353 gadolinium-containing contrast injections over a five year period. Acute allergic-like reactions occurred following 54 injections. According to the study, 48 reactions involved adults and six occurred in pediatric patients. The study showed that 74% of these reactions were mild, 19% were moderate, and 7% were severe.

“Despite recent concerns that have emerged about the gadolinium-based contrast agents and the development of nephrogenic systemic fibrosis in patients who have severe chronic kidney disease, our study supports the long-held belief that gadolinium based contrast agents can be used safely in both pediatric and adult patients with normal or with only mildly impaired renal function,” said Dr. Richard Cohan, co-author of the study. “The risk of allergic-like reactions is exceedingly low (0.07% of administrations in our study), and no fatal reaction occurred at our institution in more than 78,000 intravenous administrations. Patients should feel reassured, based on our results, that the intravenous gadolinium-contrast agents included in our study are quite safe when administered to patients with ample renal function,” he said.

The full results of this study appear in the December issue of the American Journal of Roentgenology, published by the American Roentgen Ray Society.

American Roentgen Ray Society

http://www.arrs.org

“If you have a food allergy, eating even the smallest amount of that food may trigger a serious reaction,” says James Li, M.D., Ph.D., Mayo Clinic allergy specialist, in the December issue of Mayo Clinic Women’s HealthSource. “With food intolerance, you may be able to eat small amounts of problem foods without a reaction.”

With an allergy, the immune system mistakenly identifies a food as harmful, triggering immunoglobulin E (IgE) antibodies to fight the substance. Signs and symptoms usually develop within minutes and may include tingling in the mouth, hives, swelling of the lips, face, tongue and throat, wheezing or breathing difficulties, dizziness, abdominal pain, diarrhea, nausea or vomiting. In severe cases, the airway can constrict.

Food intolerance, where a symptom is triggered by a food or substance, is much more common than food allergy. Only about 2 percent of adults and 6 percent of children have a food allergy. Food intolerance doesn’t involve the immune system but can cause some of the same gastrointestinal symptoms as food allergy. For example, lactose intolerance, where people don’t have the digestive enzymes to fully digest sugar in milk products, can cause bloating, cramping or diarrhea.

“It’s wise to consult a physician if you have concerns or questions about your reaction to certain foods,” says Dr. Li. Allergies can be diagnosed with skin and blood tests. Diagnosing food intolerance is a bigger challenge, requiring a thorough health history. Foods can trigger symptoms for a number of medical conditions, such as irritable bowel syndrome, acid reflux and migraine.

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This Phase 3 clinical trial is a 14-day randomized, double-blind comparison of two concentrations of epinastine (0.1% and 0.15%) at two different spray volumes to placebo in approximately 750 subjects who have a documented history of seasonal allergic rhinitis (SAR) to mountain cedar pollen. This 5-arm trial will be conducted at nine clinical sites during the mountain cedar pollen season, which typically begins in December in south Texas.

The primary efficacy endpoint of this trial is the average change from baseline over the 14-day treatment period for the reflective Total Nasal Symptom Score (TNSS), defined as the sum of scores for runny nose, itchy nose and sneezing. Several secondary endpoints will also be evaluated, including change in nasal and ocular symptoms, as well as quality of life parameters and safety endpoints.

“We are pleased to initiate our Phase 3 program of epinastine nasal spray and look forward to reporting top-line results in the second quarter of 2008,” stated Christy L. Shaffer, Ph.D., President and CEO of Inspire. “We believe that epinastine has the potential to offer patients an alternative to intranasal steroids for the treatment of allergic rhinitis.”

The Phase 3 program is expected to consist of three pivotal Phase 3 clinical trials, including two SAR trials and one long-term safety trial in patients with perennial allergic rhinitis (PAR). In August 2007, Inspire initiated a required 6-month intranasal toxicology study of epinastine in a single animal species and expects to have results by mid-year 2008. The results from the 6-month study are necessary to begin the long-term safety trial, which will collect one-year safety data required for a potential New Drug Application.

In 2006, Inspire acquired certain exclusive rights from Boehringer Ingelheim International GmbH to develop and market epinastine nasal spray in the United States and Canada for the treatment of rhinitis.

About Inspire

Inspire is a biopharmaceutical company dedicated to discovering, developing and commercializing prescription pharmaceutical products in disease areas with significant commercial potential and unmet medical needs. Inspire employs a U.S. sales force for the promotion of AzaSite™ (azithromycin ophthalmic solution) 1% for bacterial conjunctivitis, Elestat® (epinastine HCl ophthalmic solution) 0.05% for allergic conjunctivitis and Restasis® (cyclosporine ophthalmic emulsion) 0.05% for dry eye. Inspire is focused on the therapeutic areas of ophthalmology and respiratory/allergy, and is developing products for dry eye, cystic fibrosis, allergic rhinitis and glaucoma. Elestat and Restasis are registered trademarks owned by Allergan, Inc. AzaSite is a trademark owned by InSite Vision Incorporated. For more information, visit http://www.inspirepharm.com.

Forward-Looking Statements

The forward-looking statements in this news release relating to management’s expectations and beliefs are based on preliminary information and management assumptions. Specifically, no assurances can be made with respect to: the initiation, timing, structure or outcome of Inspire’s Phase 3 clinical program to evaluate epinastine nasal spray for the treatment of allergic rhinitis, including without limitation, the number of Phase 3 clinical trials generally, the number of Phase 3 seasonal allergic rhinitis clinical trials, the number of Phase 3 perennial allergic rhinitis clinical trials, the primary or secondary endpoints relating to any such trials, the ability of the product candidate to offer patients an alternative to intranasal steroids, the types of trials, the indications, if any, for which approval may be sought or received, the timing and scope of any mountain cedar pollen season, the timing of the initiation and expected results of a Phase 3 clinical trial during any mountain cedar pollen season, the timing or results of an intranasal toxicology study, and the timing and success of one-year safety results.

Such forward-looking statements are subject to a wide range of risks and uncertainties that could cause results to differ in material respects, including those relating to product development, revenue, expense and earnings expectations, the seasonality of Elestat, intellectual property rights, adverse litigation developments, adverse developments in the U.S. Securities and Exchange Commission (SEC) investigation, competitive products, results and timing of clinical trials, success of marketing efforts, the need for additional research and testing, delays in manufacturing, funding, and the timing and content of decisions made by regulatory authorities, including the U.S. Food and Drug Administration.

Further information regarding factors that could affect Inspire’s results is included in Inspire’s filings with the SEC. Inspire undertakes no obligation to publicly release the results of any revisions to these forward-looking statements that may be made to reflect events or circumstances after the date hereof.

‘We are particularly disappointed that the Government does not see fit to act upon the recommendations for specialist allergy centres to be set up in each region. This will make it more difficult for people with asthma to identify what their triggers are and so reduce their ability to effectively manage their condition. Currently only 30% of people with asthma tell us that they have been offered allergy testing to help them to identify what triggers their asthma, which is wholly unacceptable.

‘This is not the first time that Parliament has asked the Government to improve allergy services and it’s essential NHS services are improved as only then will people with allergic conditions get the treatment they desperately need.’

The nonprescription Zyrtec products also are approved for the relief of itching due to hives in people 6 years of age and older, including adults.

“The approval of Zyrtec for nonprescription use offers an additional treatment option for children and adults,” said Andrea Leonard-Segal, M.D., director, Division of Nonprescription Clinical Evaluation in the FDA’s Center for Drug Evaluation and Research. “As for all nonprescription drugs, consumers and caregivers should read and carefully follow all directions on the labeling.”

The tablets and chewable tablets are approved for adults and children 6 years of age and older:

- for the treatment of the symptoms of hay fever and other respiratory allergies, and
- to relieve the itching due to hives.

The syrup is approved for:

- adults and children 2 years of age and older for the treatment of the symptoms of hay fever and other respiratory allergies, and
- adults and children 6 years of age and older to relieve the itching due to hives.

The company will market two distinct Zyrtec products for each dosage form. One will provide directions for treating the symptoms of hay fever and other respiratory allergies. The other will contain directions for use to relieve the itching due to hives.

Zyrtec may cause drowsiness in some people at recommended doses. Other common side effects include fatigue and dry mouth.

On November 9, 2007, the FDA announced that it had approved Zyrtec-D, a product which contains cetirizine HCl and pseudoephedrine HCl, for nonprescription use. Sales of the Zyrtec-D are subject to restrictions in the Combat Methamphetamine Epidemic Act. This law places restrictions on the sale of products containing pseudoephedrine, such as limiting the amount that an individual can purchase, and imposing record keeping requirements on the retail establishments that sell the product and that it be located with the pharmacist. Nonprescription Zyrtec-D was approved for the relief of symptoms due to hay fever or other upper respiratory allergies such as runny nose, sneezing, itchy, watery eyes, itching of the nose or throat, and nasal congestion. Zyrtec-D is also approved for reducing swelling of nasal passages, for relief of sinus congestion and pressure, and for restoring freer breathing through the nose due to hay fever and other upper respiratory allergies. Zyrtec-D is not approved for the relief of itching due to hives.

Zyrtec is marketed and distributed by McNeil Consumer Healthcare, based in Fort Washington, Pa.