Alzheimer’s drug memantine may help prevent SCD crises, especially in kids
Study: Cheaply available therapy might be repurposed for sickle cell
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Memantine, an oral medication that’s been used for decades to help treat Alzheimer’s disease, is generally tolerated well by people with sickle cell disease (SCD) and may help prevent painful disease crises, especially in children.
Those are the findings of a small, one-year study in Israel that tested the medication’s effects, particularly its safety, in adults and children with SCD.
Although more, larger-scale research needs to be done, the results imply that this Alzheimer’s treatment — which is no longer patent-protected and can therefore be produced relatively cheaply — might be able to be repurposed as a therapy for SCD patients, the scientists noted.
According to the researchers, “memantine has the potential to become a supportive and low-cost therapy in conjunction with [SCD prescription medication] hydroxycarbamide,” also known as hydroxyurea.
The study, “MeMAGEN: A Phase IIa/IIb open-label trial of memantine testing safety and tolerability in sickle cell patients,” was published in the journal HemaSphere. by a team from institutions in Israel and Switzerland.
An inherited disorder, SCD is caused by mutations in a gene needed to produce hemoglobin, the protein that red blood cells use to ferry oxygen in the bloodstream. The mutated hemoglobin tends to form clumps in red blood cells, deforming them into the sickle shape that gives the disease its name. Sickled blood cells are prone to getting stuck in blood vessels, which can block blood flow and lead to painful episodes known as vaso-occlusive crises (VOCs).
Alzheimer’s drug memantine no longer patent-protected
Memantine is an oral therapy that’s been used since the early 2000s to help manage symptoms of Alzheimer’s, a progessive neurological disorder. It’s sold under the brand name Namenda, but the medication is no longer patent-protected and generic versions are available at a fairly low cost.
Previous studies have suggested that memantine can aid in stabilizing red blood cells, helping to prevent the clumping of mutated hemoglobin that causes disease complications in SCD. These findings have led some scientists to speculate that this cheaply available therapy might be able to be repurposed as an SCD treatment.
“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,” Max Gassmann, PhD, senior author of the study at the University of Zurich in Switzerland, said in a university news story detailing the findings.
Having a cheap, easy-to-store option could be especially important in places such as Africa and India, where SCD is common and healthcare systems often lack resources.
An earlier pilot study (NCT02615847) tested memantine in four adults with SCD, with the results indicating that the therapy was generally tolerated well. Now, researchers conducted a Phase 2 trial called MeMAGEN (NCT03247218) that tested memantine in 17 SCD patients who ranged in age from 10 to 40.
All of the patients were also taking hydroxyurea, an approved SCD treatment. Gassmann therefore noted that the study results “should … be interpreted as complementary to hydroxyurea.”
Larger studies needed to determine therapy’s benefits in SCD
The trial’s main goal was to evaluate the safety of memantine in SCD patients, and its results were generally positive — some patients reported headaches or constipation, but these were temporary and no serious side effects were reported.
Because the study was small, the researchers generally weren’t able to conduct statistically meaningful analyses to evaluate the impact of the treatments on clinical outcomes.
The team noted some promising trends, however. Of particular note, among children in the study, rates of VOCs fell from a median of five per year prior to starting memantine to one per year while on the therapy. Children also tended to have fewer days spent in the hospital while on memantine, relative to rates before starting the treatment, the data showed.
“The number of participants in the MeMAGEN trial was relatively low, and a placebo group was not included in the study, enabling us to draw only partial conclusions on the clinical efficacy of memantine therapy. Nevertheless, compared to their [two]-year medical history prior to trial enrollment, we observed a significant decrease in the number of days spent in hospital for children on memantine,” the researchers wrote.
The scientists stressed that additional, larger studies will be needed to conclusively determine whether or not memantine can benefit SCD patients. But these early findings suggest that those larger studies are worth carrying out, the researchers said.
The number of participants in the MeMAGEN trial was relatively low. … Nevertheless, compared to their [two]-year medical history prior to trial enrollment, we observed a significant decrease in the number of days spent in hospital for children on memantine.
“Knowing that memantine is safe and well tolerated, reduces hospitalization days, and improves RBC [red blood cell] rehydration, we anticipate that this drug should be tested for clinical efficacy in a larger Phase [3], double-blinded, placebo-controlled clinical trial,” the team wrote.
In addition to its demonstrated safety and tolerability, the scientists stressed that memantine is an “off-patent, inexpensive, and easily stored drug with convenient once-daily administration.”
Its low cost and generally easy availability make the Alzheimer’s drug especially attractive as a potential repurposed therapy for SCD, the team concluded, adding that “it represents a particularly promising option for patients in low-income regions, where SCD remains highly prevalent and often insufficiently treated.”
