The ARMED Project

Microvillous Inclusion Disease (MVID) is a very rare and serious genetic intestinal disorder affecting infants and young children. The degeneration of their small intestine results in patients' inability to absorb nutrients from their diet, making them dependent on parenteral nutrition throughout their lives.

Recently, we identified a cellular defect in MVID that is responsible for small bowel degeneration and, importantly, could be treated with the antioxidant N-acetylcysteine (NAC) in a mouse model of MVID. NAC is an inexpensive, safe and EMA/FDA-approved drug, primarily indicated for the treatment of paracetamol intoxication. Although the reuse of NAC for the treatment of MVID seems appropriate, a clinical study in MVID patients is not trivial. The long-term effects of NAC in the gut are unknown. Furthermore, NAC is contraindicated for children under 2 years of age.

In the proposed study, we aim to optimize NAC treatment and identify alternative antioxidant drugs for children of all ages using human cell lines, organoids and animal models of MVID. In addition, we intend to evaluate the most effective drug formulation, dose and route of administration suitable for MVID patients.

The results obtained from this study will pave the way for a first-in-man clinical trial, with the long-awaited prospect of improving nutrient absorption and reducing the need forintravenous feeding, thereby increasing the life expectancy and quality of life of MVID patients.

The project was funded by: