ARMED: Antioxidant treatment as a novel therapeutic option for microvillus inclusion disease

Microvillus inclusion disease (MVID) is a very rare and severe genetic bowel disorder that affects infants and young children. Degeneration of their small intestine causes the patients’ inability to absorb nutrients from the diet and makes them life-long dependent on intravenous feeding. Unfortunately, most patients also die from the severe complications that accompany long-term intravenous feeding. Recently, we have identified a cellular defect in MVID that is accountable for the degeneration of the small intestine and, importantly, could be treated with the antioxidant N-acetylcysteine (NAC) in a mouse model of MVID. NAC is an inexpensive, safe, EMA/FDA-approved drug primarily indicated for the treatment of paracetamol intoxication. Although repurposing of NAC for the treatment of MVID seems fitting, a clinical study in MVID patients is not trivial. NAC is contraindicated for children under the age of 2 and therefore may not represent the best choice for the treatment of MVID in infants. In the proposed study, we aim to identify other antioxidant drugs that can be used in children of all ages by using human cell lines, organoids and animal models of MVID. Moreover, we intend to evaluate the drug formulation, dose and route of administration that are most efficient and suitable in MVID patients. The results obtained from this study will pave the way for a first-in-human clinical trial with the long-awaited prospect of improving nutrient absorption and decrease the need for intravenous feeding, ultimately increasing life expectancy and quality of life for MVID patients.