ABSTRACT Administration of memantine, an antagonist of the N ‐methyl‐ d ‐aspartate receptor, prevents Ca 2+ overload and dehydration of red blood cells (RBCs) in patients with sickle cell disease (SCD). The objectives of the 1‐year dose‐escalation Phase IIa/IIb Memantine trial (MeMAGEN – NCT 03247218) with 17 SCD patients who were under stable hydroxycarbamide therapy were to test the drug's safety and tolerability. Daily memantine doses ranged from 5 to 15 mg for children/adolescents and from 5 to 20 mg for adults. Clinical and laboratory analysis showed that memantine was well tolerated. In children, a decrease in days spent in the hospital was observed. Safety was confirmed by laboratory tests, which were not, or were only minimally, altered during memantine therapy. In a subgroup of six patients whose RBCs presented with elevated K + leakage before treatment, memantine therapy at its lowest dosage reduced this K + loss and increased hemoglobin concentration. This study shows that memantine is safe and well tolerated by SCD patients, including children. Memantine has the potential to become a supportive and low‐cost therapy in conjunction with hydroxycarbamide.
Koren et al. (2026) studied this question.