PRT100 Mechanism of Action
Principle: Probiotics (live biotherapeutic products) are live non-pathogenic microorganisms that benefit the health of the host when administered in adequate amounts. Probiotic bacteria have potent documented immune modulatory effects. In particular, the probiotic used in Prota’s therapy, PRT100, has been shown to have immunomodulatory effects in vitro and in vivo that support acquisition of oral tolerance, including induction of T regulatory cells (Treg) and Treg and Th1 cytokine responses, and enhancement of antigen-specific IgA responses. Through these actions of the probiotic, PRT100 redirects the peanut specific immune response away from allergy towards tolerance.
PRT100 REDIRECTS THE IMMUNE RESPONSE FROM ALLERGY towards TOLERANCE
Mechanism: In allergic individuals, an inappropriate T helper 2 (Th2) response has developed to the food allergen(s) leading to production of peanut-specific IgE antibodies and differentiation of mast cells. Upon re-exposure to peanut, peanut allergens bind to peanut specific IgE antibodies on the surface of the mast cells, and crosslinking of adjacent IgE antibodies results in activation of mast cells, triggering the release of mast cell mediators which in turn lead to the symptoms of an allergic reaction.
The immune modulating actions of the probiotic in PRT100 direct the immune system to respond differently to peanut allergen, supporting a tolerance-type response in place of an allergic response. Over time there is redirection of the peanut specific immune response away from allergy towards tolerance. Clinical studies have shown that children who responded to PRT100 treatment with long-term sustained unresponsiveness 4 years after treatment had negative peanut skin prick tests and blood levels of Ara h 2 sIgE, indicating long-term remission of peanut allergy.
Approach: Prota Therapeutics is developing an innovative novel treatment for peanut allergy, based on 2 decades of research by the company’s scientific founder, Prof Mimi Tang, which combines a probiotic together with peanut allergen OIT. To date, this therapy has resulted in the best response rates of sustained unresponsiveness reported for any food allergy therapy in development and is the only therapy in development that has been shown to induce long-term sustained unresponsiveness / long-term remission of allergy.
Administration of PRT100 has been shown to:
- reduce peanut skin prick test wheal size,
- reduce peanut specific IgE levels in the blood,
- increase peanut specific IgG4 levels in the blood, and
- enhance peanut-specific IgA responses,
suggesting redirection of the peanut-specific allergic response towards tolerance. Further investigation of the mode of action of PRT100 and effects on the intestinal microbiome are underway.