A double-blind, placebo-controlled, crossover study of magnesium supplementation in patients with XMEN syndrome: preliminary results

Introduction X-linked immunodeficiency magnesium defect, Epstein-Barr virus (EBV) infection and neoplasia (XMEN) syndrome is a primary immunodeficiency caused by the loss of expression of the magnesium transporter 1 (MAGT1). This syndrome is associated with CD4 lymphopenia, chronic EBV infection in most patients, and EBV related lympho proliferative disorders. The loss of MAGT1 leads to impaired T cell activation and decreased expression of the activator receptor, NKG2D on natural killer (NK) cells and CD8 T cells, leading to decreased EBV-specific cytolytic function of these cells. Results of previous studies suggest that magnesium supplementation may be a viable therapeutic option for patients with XMEN. Methods Patients ≥6 years of age with XMEN syndrome and persistent EBV viral load of ≥5,000 copies/mL by whole blood PCR are randomized to receive escalating doses of either placebo or oral magnesium L-threonate for 12 weeks. This is followed by crossover treatment for an additional 12 weeks. For patients who experience a 0.5-log decrease in the number of EBV-infected B cells by FISH with oral magnesium as compared to placebo, the study is complete. Patients who do not meet this outcome then undergo a 2-week washout period and proceed to Part II, an open-label, non-randomized evaluation of intravenous magnesium sulfate (MgSO4) followed by oral magnesium L-threonate. Results here we report the preliminary results for the first patient enrolled in the clinical trial, including changes in the number of EBV infected B cells and NKG2D expression with magnesium treatment.