FAI Researchers Explore New Therapies
Three new FAI-sponsored projects could lead to exciting new treatments—immunotherapies that could change food allergy sufferers’ lives. An immunotherapy is a treatment that teaches your immune system to tolerate substances that trigger allergic reactions. Perhaps the best-known form of immunotherapy is the “allergy shot.” For years, this type of vaccination has been the key treatment for environmental allergies, such as hay fever, which is caused by pollens. But developing a safe and effective immunotherapy for food allergies has been a major challenge for researchers.
Allergies happen when the immune system becomes overactive and misdirected. As a result, it attacks harmless proteins such as those in foods, pollens, or animal dander. To tame this overactive response, immunotherapy gradually exposes your immune system to increasingly larger doses of the allergen. Eventually, your immune system learns to accept the allergen instead of attacking it. This process is known as immune tolerance. Fortunately, exposure to environmental allergens isn’t typically dangerous, and relatively small doses can effectively establish immune tolerance. But food allergens are different, since even trace amounts of problem foods can trigger anaphylaxis. In fact, when researchers tried to develop shots for food allergies, they had to discontinue their studies because the participants experienced severe reactions.
Now, armed with new technologies and information about how the immune system functions, researchers are working to develop effective immunotherapies that eliminate the threat of anaphylactic reactions to food. Many of the studies are focusing on peanut, largely because the allergy is common and often severe, and research tools such as mouse models and characterized proteins are readily available. However, the therapies being studied could be adapted to treat other food allergies as well.
Antigen-Specific Tolerance Therapy
At Chicago’s Northwestern University Feinberg School of Medicine, Dr. Paul Bryce, a food allergy expert, has joined forces with Dr. Stephen Miller, an immunobiologist. Dr. Miller and his colleagues have developed a therapy that “turns off” specific T cells, which play a role in multiple sclerosis and type 1 diabetes. This new approach, known as antigen-specific tolerance therapy, has been successful in mouse models of these diseases, and human trials are in the planning stage. Preliminary data shows that this therapy may have potential for asthma as well. Like food allergies, all three illnesses represent a misdirected immune response. Drs. Bryce and Miller believe that antigen-specific tolerance therapy may be a safe and effective option for food-allergic patients.
Dr. Bryce has developed a mouse model that mimics food allergies in humans. The researchers are using the new therapy to treat the mice, which develop severe egg or peanut allergy. One set of these mice will be sensitized to egg or peanut before they are given the treatment. If these mice do not go on to develop food allergies, it could mean that this therapy has potential as a vaccine that prevents the disease in people who are at high risk. Another group of mice will be given the therapy after they develop food allergies. If the treatment safely restores tolerance in these mice, it might become the basis for new immunotherapies that control symptoms in people who already have food allergies.
Allergen Gene Vaccination
At UCLA, Drs. Andrew Saxon and Zhang Ke are exploring another potential immunotherapy, known as allergen gene vaccination. As we have seen, in previous attempts to develop a food allergy vaccine, patients were given food allergen proteins, which caused severe reactions. A vaccine that employs food allergen genes, rather than proteins, could make a crucial difference.
The key to this therapy is to target good allergen genes to specific cells of the immune system known as APCs (allergen-presenting cells). Research has shown that when APCs are expressing food allergen genes, they may protect against food allergies. However, when the genes are injected into the body, they don’t always connect with the APCs. Drs. Saxon and Ke are developing a genetically engineered vaccine that would ensure that APCs attach themselves to peanut allergen genes. The goal of their FAI-funded study is to test the vaccine in a mouse model of peanut allergy, developed with FAI funding by Dr. Jean-Pierre Kinet (Beth Deaconess Medical Center/Harvard Medical School, Boston). The researchers hope to prove that allergen gene vaccination triggers a protective immune response and effectively treats peanut allergy in these mice. If successful, this study could lead to clinical trials and, ultimately, to a vaccine for peanut and other food allergens.
Helminth Therapy
Dr. Kinet recently received FAI funds for a fascinating new project. He is studying a new immunotherapy that contains the eggs, or ova, of a helminth—a parasitic worm called Trichuris suis (the pig whipworm). Although Trichuris suis ova (TSO) therapy may sound strange at first, it has already shown promise in treating other immune-related illnesses, including multiple sclerosis, as well as two serious digestive diseases, Crohn’s disease and ulcerative colitis. Dr. Kinet’s study would be the first to test TSO in food allergies.
The "hygiene hypothesis" is the basis for TSO therapy. According to this theory, advances in hygiene are responsible for the increase of allergies and autoimmune diseases in developed countries. Until the 20th century, people were routinely exposed to helminths and other parasites, bacteria, and viruses, which presumably occupied the immune system and reduced the chance that it would attack harmless proteins in the environment (allergy) or in one’s own body (autoimmune disease). Thus, therapies that reintroduce helminths may safely redirect the immune response, alleviating the symptoms of food allergies.
There are many different types of helminths. TSO was chosen because it does not cause disease in people, does not multiply in a person’s system, and cannot be transmitted to other people. A vial contains the correct dosage of the eggs, which are virtually microscopic. The patient mixes the contents of the vial with water or juice and drinks the solution.
In this pilot study, Dr. Kinet will determine definitively whether or not TSO is safe to administer to peanut-allergic patients. The treatment will be given to five children and five adults with peanut allergy. The study also will provide preliminary data to support TSO’s effectiveness. Once they demonstrate the safety of the treatment, Dr. Kinet and his colleagues will launch a clinical trial, which will test the effectiveness of TSO in an estimated 58 patients.
As these new studies demonstrate, FAI is sponsoring more innovative and sophisticated research than ever before. View the complete list of FAI-funded research projects.