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Memantine, a long-approved and cost-effective drug used to treat Alzheimer’s disease, could also benefit patients with sickle cell anemia in the future. Initial clinical data from an international research group led by the University of Zurich (UZH) indicate that the active ingredient is well tolerated, reduces symptoms and improves quality of life in people suffering from this genetic disease.
Sickle cell anemia is the world’s most common genetic disorder. It causes the red blood pigment hemoglobin to crystallize, which results in rigid, malformed red blood cells with a sickle shape. This impairs the cells’ mobility and causes severe complications, including circulatory disorders, organ failure, a significantly shortened life expectancy and reduced quality of life – especially in children and adolescents.
The disease, which is hereditary, can be treated with hydroxyurea. When taken regularly, this drug can improve quality of life; however, it is not well tolerated by all patients. A bone marrow transplant is another possibility, but there is a lack of suitable donors and other treatments, such as gene therapies or therapeutic antibodies, come with extremely high costs. Now, an international team led by Max Gassmann, professor emeritus of veterinary physiology at the University of Zurich, is pursuing an alternative and significantly more cost-effective approach. More specifically, they are investigating the potential application of the Alzheimer’s drug memantine in the treatment of sickle cell anemia, a use outside its approved indication. Memantine has been used to treat Alzheimer’s disease for about 20 years, meaning it is no longer patentable.
The potential of an inexpensive active ingredient
In previous preclinical studies, researchers demonstrated that memantine has a stabilizing effect on red blood cells. They then investigated the drug’s safety and tolerability in a phase II study. “In the best case, memantine would be available for the treatment of sickle cell anemia, as a well-tolerated, easy-to-store, and very cost-effective drug that is no longer patent-protected,” says Max Gassmann. This would be particularly significant for countries with a high disease burden and limited resources, for example Africa or certain places in India.
Fewer and shorter hospitalizations
A total of 17 study participants received age-appropriate doses of memantine for 12 months. The research team took several key findings from the study: the treatment was well tolerated, and more than 25 laboratory parameters confirmed the drug’s safety over a period of two to three years. At the same time, a clear clinical benefit was demonstrated: both the number and duration of hospitalizations decreased significantly. Children in particular experienced fewer painful flare-ups. No serious side effects or discontinuations of the study due to the therapy itself were observed.
Follow-up study planned
All patients involved in the study continued their existing hydroxyurea therapy, as discontinuing it would have been unethical. “The observed effects should therefore be interpreted as complementary to hydroxyurea,” Gassmann explains. The research team is now planning a follow-up study that will, for the first time, include patients who have not received hydroxyurea treatment, in order to allow a systematic analysis of combination therapies. This approach aims to evaluate the clinical efficacy of memantine in a comprehensive and evidence-based way.
References
Ariel Koren, Carina Levin, Leonid Livshits, Fabio Valeri, Sari Peretz, Sivan Raz, Anna Yu. Bogdanova, Max Gassmann. MeMAGEN: a phase IIa/IIb open-label trial of memantine testing safety and tolerability in sickle cell patients. HemaSphere. 11 January 2025. DOI: 10.1002/hem3.70278
Contact
Prof. emeritus Prof. h.c. Dr. Max Gassmann
Institute of Veterinary Physiology
University of Zurich
+41 44 635 88 03
E-mail: maxg@access.uzh.ch
Prof. emeritus Prof. h.c. Dr. Max Gassmann
Institute of Veterinary Physiology
University of Zurich
+41 44 635 88 03
E-mail: maxg@access.uzh.ch
Ariel Koren, Carina Levin, Leonid Livshits, Fabio Valeri, Sari Peretz, Sivan Raz, Anna Yu. Bogdanova, Max Gassmann. MeMAGEN: a phase IIa/IIb open-label trial of memantine testing safety and tolerability in sickle cell patients. HemaSphere. 11 January 2025. DOI: 10.1002/hem3.70278
https://www.news.uzh.ch/en/articles/media/2026/Sickle-Cell-Anemia.html
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