14 DAY TRIAL // Scientists at Sanford-Burnham have carried out a study that explains exactly how memantine, the drug used to treat Alzheimer's disease, works and why its side effects are rare.
Alzheimer's disease damages brain cells as well as their connections, called synapses, and causes memory loss and several other cognitive problems that interfere with patients' daily life.
Currently, the most effective treatment is provided by the drug memantine, that is FDA-approved to treat moderate-to-severe Alzheimer’s disease and that helps ease the symptoms.
Stuart A. Lipton, MD, PhD, Director of the Del E. Web Center for Neuroscience, Aging and Stem Cell Research at Sanford-Burnham Medical Research Institute, took part at the development of memantine (marketed in the United States as Namenda) and now at the study investigating how the drug works, without causing side effects.
The study that appeared yesterday (August 18) in The Journal of Neuroscience, established that memantine blocks the abnormal activity of glutamate, a chemical that transmits messages between nerve cells, thus improving the symptoms of the disease.
Dr Lipton said that “While memantine is partially effective in treating Alzheimer’s disease, one of its major advantages is how safe and well-tolerated it is clinically.”
The reason for which memantine does not have serious side effects is because it inhibits excessive glutamate signaling occurring away from the synapses without blocking the activity of glutamate at the synapses, allowing normal brain activity.
When creating a new drug, it is rather difficult to maximize its beneficial effects and minimize its harmful side effects, so Dr Lipton is quite proud of the development of memantine.
“We showed definitively for the first time that memantine, the drug our group developed for Alzheimer's disease, works in a unique way.
“It inhibits a protein that binds glutamate called the NMDA (N-methyl-D-aspartic) receptor, but predominantly blocks NMDA receptors that signal molecularly to cause neuronal injury and death, and it spares the synaptic receptors that mediate normal communication between nerve cells in the brain.”
This explains why memantine is so well tolerated by Alzheimer's patients and it could open the way to future therapies that target the NMDA receptor.
In the United States, 5.3 million Americans are living with Alzheimer's, and the disease is now the seventh-leading cause of death.
This study was supported by grants from the National Institute for Neurological Diseases and Stroke, the National Eye Institute and the Eunice Kennedy Shriver National Institute of Child Health & Human Development, as parts of the National Institutes of Health, and the American Heart Association.