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Popular Alzheimer’s drug shows promise in clinical trials for treating patients with sickle cell disease

Popular Alzheimer’s drug shows promise in clinical trials for treating patients with sickle cell disease

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A popular drug commonly used to treat Alzheimer’s disease has shown promise in laboratory and clinical trials for treating patients with sickle cell disease (SCD). Researchers have found that the molecule memantine stabilizes the development, longevity and function of red blood cells and is well-tolerated by SCD patients. The findings will be presented today at the American Physiological Society’s Physiological and Pathophysiological Consequences of Sickle Cell Disease conference in Washington, D.C.

SCD affects millions globally and an estimated 100,000 people in the U.S. There is currently only one drug approved by the U.S. Food and Drug Administration (hydroxycarbamide) for the treatment of SCD. Hydroxycarbamide-;a so-called “small molecule” therapy for SCD-;was approved for medical use in 1967, but no other drugs have been introduced despite growth in disease prevalence and an increase in patient lifespan.

SCD is marked by problems with the development and function of red blood cells, which lead to pain and other complications that can involve almost every organ system in the body.

A team of Swiss researchers affiliated with the Red Cell Research Group discovered that ion channels in red blood cells of people with SCD were 10 times more likely to take up excessive calcium. “Calcium overload in turn has multiple deleterious consequences, including loss of water and facilitation of ‘sickling,’ oxidative stress and increased adhesiveness of such red cells to each other and blood vessel walls,” explained the study’s lead researcher, Anna Bogdanova, PhD. The behavior of the red blood cells is related to the health complications that SCD patients face, such as pain, blood clots and organ problems.

In searching for an alternative treatment for SCD, the research team explored NMDA blockers as a potential target for drug therapy. NMDA is a type of amino acid that is found in high abundance in red blood cells of patients with SCD. Antagonists, such as memantine, have been used in other disease models to block NMDA receptors in the brain. “Memantine has been used for decades for treatment of Alzheimer’s disease and dementia worldwide. It has proven to be safe, is off-patent and produced as generic by multiple companies,” Bogdanova said. “Experiments in which we exposed blood of sickle cell disease patients to memantine revealed less oxidative damage and sickle cell transformation.” As a next step, hematologists at the University Hospital Zurich initiated a pilot clinical trial. Within this phase II trial, six adults with SCD were treated with memantine for 12 months.

“We have proven safety and tolerability of memantine by sickle cell disease patients,” Bogdanova said. “The trial participants reported substantial improvements in quality-of-life scores and expressed that they had a ‘good year.’ This was supported by the observations shown by the clinical and research laboratory red cell parameters monitored during the MemSID study.

“Taken together, the findings reveal reduction in hemolytic activity, stabilization of red cell membrane and increased longevity of red cells, and suppression of ineffective red blood cell production (erythropoiesis). We are inspired by this promising outcome and are initiating a follow-up phase II trial defining optimal dose of memantine to support stabilization of red cells in 40 to 50 adult and adolescent patients with sickle cell disease this December. If successful, this trial will allow us to use this small and inexpensive molecule to improve quality of life of patients with sickle cell disease worldwide,” Bogdanova said.​

Source:

http://www.the-aps.org/mm/hp/Audiences/Public-Press/2017/70.html

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