Currently, the primary treatment for celiac disease (CD) is a strict and lifelong gluten-free diet, which can saddle patients with heavy financial and social burdens. On top of this, many patients continue to get exposed to gluten accidentally, preventing their intestines from healing properly. Other forms of treatment, such as Alvine Pharmaceutical’s ALV003, are being investigated as possible supplements to the gluten-free diet to help protect patients against exposure to small amounts of gluten. Another group of researchers recently published an article detailing their examination of another possible treatment to accompany the gluten-free diet.
The researchers, led by first-authors Dr. John Croese and Dr. Paul Giacomin, were looking into how hookworm infection affects CD patients’ response to gluten. Dr. Croese was involved in a previous study of hookworms in CD patients from 2011. In that double-blinded, placebo-controlled study, 10 CD patients with a hookworm infection were given a five day gluten challenge of 16 grams of gluten per day. The results showed little difference in the patients histology compared to the control group. However, Croese and his colleagues did conclude that hookworm infection was safe to use for future experiments, and also that the hookworm infection helped suppress the expression of certain proteins associated with CD.
In this most recent article, published by the Journal of Allergy and Clinical Immunology in September 2014, Croese and Giacomin tried a different strategy than just a normal gluten challenge in CD patients. The article, titled “Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease,” relied on CD patients infected with hookworm, undergoing a gluten micro-challenge for several weeks before a normal gluten challenge. The primary endpoint of the experiment was villous height: crypt depth ratio (Vh:Cd).
The researchers found that after several weeks of the gluten challenge (25 milligram of gluten daily, plus 1 gram of gluten twice weekly), Vh:Cd remained virtually unchanged. In previous experiments by other researchers, Vh:Cd declined up to 20% after a 50 milligram gluten challenge, so the lack of any change was quite significant. When the researchers saw the improved gluten tolerance of the patients, they decided to try another gluten challenge of three grams of gluten a day, following another micro-challenge, and found that the presence of tissue transglutaminase antibodies actually decreased, as opposed to increasing in previous studies.
The authors point out that this study has several weaknesses: it was small in size, had exclusions that probably improved the results, and was not double-blind/placebo-controlled like the previous study by Dr. Croese. However, the improvement in gluten tolerance was readily apparent in the results, and the authors suggest future, more rigorous studies be performed to confirm their results and measure the efficacy of the hookworm/microchallenge treatment. They also point out that this treatment is not an alternative to the gluten-free diet, but potentially a supplement to help protect CD patients against accidental gluten exposure.