San Francisco, CA, October 4, 2006 -- The results of an Immune Tolerance Network (ITN) study, published in the October 5, 2006 issue of the New England Journal of Medicine suggest that a six-week experimental allergy treatment can relieve hay fever symptoms for at least two years. The researchers believe that the six-injection immunotherapy regimen with a novel DNA-based drug known as 'AIC' could offer a significant improvement over traditional allergen immunotherapy, which can require several years of weekly or bi-weekly injections.
The placebo-controlled, double blinded study, begun in 2001, examined 25 ragweed allergic (hay fever) volunteers at Johns Hopkins Asthma & Allergy Center in Baltimore, MD. Participants receiving a short, six week regimen with AIC prior to the initial allergy season showed substantially lower nasal hay fever symptoms, used less allergy medication and had higher quality of life scores than those receiving a placebo. Symptomatic improvements in AIC-treated patients were found to be maintained during the next subsequent ragweed season, despite no further treatment of these individuals.
Standard immunotherapy is a long-established treatment with proven clinical benefits for a number of allergic conditions, including hay fever. Patients receive regular injections containing small amounts of the offending allergen – ragweed pollen, in the case of hay fever - eventually making them less sensitive to inhalation of the allergen. While proven effective and long-lasting, patients require several years of weekly or monthly injections and are often unable to complete the treatments. Standard immunotherapy also carries the risk of a serious allergic reaction to the injected allergen.
In the current study, no serious adverse reactions due to AIC were observed. Side effects of the treatment were generally mild and limited to temporary redness around the injection site.
Peter Creticos, MD, Johns Hopkins researcher and principal investigator of the trial believes that this study represents an important advance in allergy therapy.
"Effectively, we have shown that it may be possible to safely reduce the treatment time for ragweed allergy from several years down to six weeks," said Creticos. "And we're not just treating the symptoms, we're targeting the fundamental defects in the immune system that cause allergy."
AIC is a novel DNA-based drug developed by Dynavax Technologies Corporation of Berkeley, CA. Short for "Amb a 1 immunostimulatory sequence conjugate", AIC contains a short piece of DNA known as an "immunostimulatory sequence" that can modify immune system reactions. In AIC, this immunostimulatory DNA sequence is linked to a portion of the molecule that causes ragweed allergy (known as 'Amb a1').
Allergies are caused by an over-reaction of the immune system to an otherwise harmless substance, such as tree and plant pollens. In allergic individuals, antibodies known as IgE are responsible for mediating the allergic response. In the current study, the researchers found that, like standard immunotherapy, AIC blocks the seasonal rise in ragweed-specific IgE in allergic individuals. They also discovered an apparent reduction in IL-4, an immune system messenger that helps immune cells known as basophils migrate to nasal tissues where they cause inflammation. Together, the researchers believe these results hint that AIC is successfully reprogramming the immune system to tolerate the presence of allergen, without over-reacting.
"Re-establishing immune tolerance to allergens really is the ultimate goal in allergy research," said University of California, San Diego's David Broide, MD, co-author and senior ITN advisor. "Based upon these findings, we appear to be taking a large step towards this goal."
This study was conducted by the Immune Tolerance Network, and sponsored by the National Institute for Allergy and Infectious Diseases (NIAID), an institute of the National Institutes of Health.
Doctors Broide and Creticos are now embarking upon a follow-up ITN/NIAID-sponsored study to determine whether the benefits of AIC treatment extend to a specific type of asthma. The "AIRIA Study" will examine the efficacy of AIC in 140 individuals with fall seasonal asthma – asthma sufferers whose condition worsens in the fall due to an underlying ragweed allergy. The researchers are seeking volunteers to participate in the multicenter study, which is being conducted at clinical centers in Baltimore, MD, Cincinnati, OH, Columbus, OH and Hershey, PA. More information can be found at www.seasonal-asthma.org or by calling toll-free, 1-888-909-4949.
About the Immune Tolerance Network
Headquartered at the University of California, San Francisco, the Immune Tolerance Network is an international collaboration of researchers that conducts clinical research of new immune tolerance therapies – highly targeted treatments that prevent harmful immune responses, while leaving the protective immune response unhindered. Targeting autoimmune diseases, islet, kidney and liver transplantation and allergy and asthma, the ITN is supported by the National Institute for Allergy and Infectious Diseases and the National Institute for Diabetes and Digestive and Kidney Diseases, and partners with the Juvenile Diabetes Research Foundation for type 1 diabetes research. www.immunetolerance.org
Disclosure: Dr. Creticos was a paid consultant to Dynavax Technologies Corporation from 1999-2004 at the time this study was conducted.
Journal
New England Journal of Medicine