A new, experimental treatment for celiac disease has finished the very early stages of testing, according to its manufacturer, ImmusanT. Unlike other treatments for celiac disease that are being developed, the product, called NexVax2, is an injectable drug designed to prevent the immune reactions that occur in people with celiac disease who consume gluten.
People who are genetically predisposed to have celiac disease react to the parts of the protein in wheat gluten called gliadins, which activate an immune response. The immune response includes the release of many inflammatory chemicals and the influx of certain kinds of white blood cells into the lining of the small intestine. All of this causes damage to the lining of the small intestine, leading to the symptoms and problems found in celiac disease.
The new drug was developed to try and prevent the activation of the immune system in people with celiac disease, by convincing the body not to react to the gliadin pieces in an abnormal way. It is designed to “trick” the body into recognizing these pieces of protein as normal and not dangerous. This is similar to the way allergies are treated with allergy shots. Although it is being called a vaccine, it actually requires many more injections than a vaccine and is also more like allergy shots in that respect – both require repeated injections.
With allergy shots, very small amounts of the substances that trigger a person’s allergies are injected under the skin one to two times a week, in slowly increasing amounts until enough is given to do what is called “induce tolerance.” The increasing amounts retrain the immune system to accepting the allergic substances as not threatening. This works for a number of allergic conditions.
Allergy shots have been in use for a long time. More recently, the same type of technique has been employed for people with food allergies by giving them minute amounts of the problem foods orally and slowly increasing the amounts until they become tolerant of the food. There is ongoing research with a number of foods known to cause allergic reactions in a significant number of people, including eggs and peanuts.
Applying this approach to celiac disease is more complicated. The pieces of gliadin need to get to the right cells. In this case, three gliadins known to cause reactions in people with celiac disease who are HLA-DQ2 positive (which is most people with CD) have been synthesized for use in the “vaccine.” They are injected repeatedly with the idea of creating tolerance to them.
There would be two steps to this process, which is again similar to the approach taken with allergy shots. In the first step, the vaccine is given frequently enough to lead to tolerance. The suggestion now is that might take two shots a week for eight weeks. After that, there would be booster shots to make sure tolerance continues. The exact specifics of this have yet to be studied because the current Phase 1b studies are simply looking at the safety of a number of dosages of the vaccine.
If this approach works, it would actually modify the disease. Theoretically, it could prevent any reaction from occurring. However, if it works as well as other similar treatments, it would only make a reaction less likely and make a person tolerant to some amount of the offending substances without being a complete cure.
The key is the delivery of the three pieces of gliadin. This process of developing the vaccine started when immunologist Bob Anderson first discovered the offending sequences of amino acids, and then went on to synthesize them. Eventually his discoveries and businesses he formed joined with others who saw the potential in the work, and the company ImmusanT was founded. Funding was obtained to develop and test ways to deliver the pieces of gliadin in such a way as to convince the body that they are not dangerous.
Two phase 2b trials are ending now and results are expected in the next few months. These trials were designed to test the safety of NexVax2 and check which doses can be used. If the results are positive, the company will work along with the FDA to plan the next step of investigation.
If the results are positive, new studies will be set up and participants recruited. If you have celiac disease and are interested in participating in a clinical trial, keep your eyes open for news of this or any other new study. Studies recruiting participants can usually be found on the NIH site ClinicalTrials.gov .