Memantine for Sickle Cell Disease

Memantine, commonly used to treat symptoms of Alzheimer’s disease, has also shown potential in a small clinical trial in patients and in preclinical studies to treat sickle cell disease.

Treatment options for sickle cell patients are limited. In fact, until Endari was approved by the U.S. Food and Drug Administration in July 2017,  hydroxyurea was the only sickle cell therapy. (Endari, the first new disease treatment in nearly 20 years, is designed to reduce complications associated with sickle cell disease in patients age 5 and older.)

How Memantine works

Sickle cell disease results from a mutation in the gene that produces hemoglobin, the iron-rich compound that allows red blood cells to transport oxygen throughout the body. The defect causes hemoglobin to crystalize and red blood cells to assume a sickle shape and become “sticky” so that they adhere to vessel walls and block blood flow.

Calcium ions, along with other metals in blood, play a vital role in many functions. In sickle cell patients, red blood cells were shown to be 10 times more likely to take up calcium than cells of healthy individuals. Excess calcium in blood cells can cause the cells to dehydrate, and can further aggravate and worsen their sickle shape, stickiness, and levels of oxidative or metabolic stress.

NMDA receptors are glutamate (an excitatory neurotransmitter) receptors on the surface of nerve and heart cells that were recently also found on blood cells. When this receptor is activated, calcium ions can enter the cell. In sickle cell patients, the NMDA receptors on red blood cells are over-active, leading to too much calcium intake. Memantine inhibits, or blocks, the receptor, preventing calcium ions from entering the cell. Studies have shown that memantine rehydrates red blood cells in patients with sickle cell disease, helping to prevent them from assuming a sickle shape.

Memantine in clinical trials

A pilot Phase 2 clinical trial (NCT02615847) of memantine took place in Switzerland between 2015 and 2017. Six adult sickle cell disease patients received 20 mg a day for 12 months. Researchers studied its effectiveness and safety, and patients’ ability to tolerate it.

Study results showed that memantine was safe in these people, and that patients reported a significantly improved quality of life. The therapy led to fewer red blood cells rupturing, allowing the cells to live longer, and decreased the production of abnormally shaped cells.

A larger Phase 2 trial (NCT03247218), called MeMAGEN, is now underway at a single site in Israel, involving up to 40 sickle cell patients. They are being divided into two groups: ages 10 to 17 and adults ages 18 and older. Participants will be given memantine tablets at doses of 5 mg, 10 mg, or 20 mg daily for a year, then followed for another three months.

The trial’s primary objective is to assess how many adverse events the treatment generates, and their severity. A secondary goal is to determine if memantine benefits patients by treating the disease, as measured by number of hospital visits, needed transfusions, lost work days, and quality of life during the trial period. This study is expected to conclude in December 2020.


Last updated: Jan. 13, 2019


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