The molecular processes that lead to Alzheimer's begin years before symptoms appear. Researchers have now found that an FDA-approved drug, memantine, currently used only for alleviating the symptoms of moderate-to-severe Alzheimer’s disease, might be used to prevent or slow the progression of the disease if used before those symptoms appear. The research also offers, based on extensive experimentation, a hypothesis as to why this might work.
The findings are published currently online in the journal Alzheimer’s & Dementia.
Prevent it from starting in the first place
“Based on what we’ve learned so far, it is my opinion that we will never be able to cure Alzheimer’s disease by treating patients once they become symptomatic,” said George Bloom, a UVA professor and chair of the Department of Biology, who oversaw the study in his lab. “The best hope for conquering this disease is to first recognize patients who are at risk, and begin treating them prophylactically with new drugs and perhaps lifestyle adjustments that would reduce the rate at which the silent phase of the disease progresses.“Ideally, we would prevent it from starting in the first place.”
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Brain Neurons Attempt to Divide
As Alzheimer’s disease begins, there is a lengthy period of time, perhaps a decade or longer, when brain neurons affected by the disease attempt to divide, possibly as a way to compensate for the death of neurons. This is unusual in that most neurons develop prenatally and then never divide again. But in Alzheimer’s the cells make the attempt, and then die.
George Bloom’s lab specializes in understanding the biochemical changes that lead to Alzheimer’s disease. (Photo by Dan Addison, University Communications)
Memantine blocks cell cycle reentry
Erin Kodis, a former Ph.D. student in Bloom’s lab and now a scientific editor at AlphaBioCom, hypothesized that excess calcium entering neurons through calcium channels on their surface drive those neurons back into the cell cycle. This occurs before a chain of events that ultimately produce the plaques found in the Alzheimer’s brain. Several experiments by Kodis ultimately proved her theory correct.The building blocks of the plaques are a protein called amyloid beta oligomers. Kodis found that when neurons are exposed to toxic amyloid oligomers, the channel, called the NMDA receptor, opens, thus allowing the calcium flow that drives neurons back into the cell cycle.
Memantine blocks cell cycle reentry by closing the NMDA receptor, Kodis found.
Giving Memantine Long Before Symptoms
“The experiments suggest that memantine might have potent disease-modifying properties if it could be administered to patients long before they have become symptomatic and diagnosed with Alzheimer’s disease,” Bloom said. “Perhaps this could prevent the disease or slow its progression long enough that the average age of symptom onset could be significantly later, if it happens at all.”Side Effects are Modest
Side effects of the drug appear to be infrequent and modest.Bloom said potential patients would need to be screened for Alzheimer’s biomarkers years before symptoms appear. Selected patients then would need to be treated with memantine, possibly for life, in hopes of stopping the disease from ever developing, or further developing.
Not to Raise False Hopes
“I don’t want to raise false hopes,” Bloom said, but “if this idea of using memantine as a prophylactic pans out, it will be because we now understand that calcium is one of the agents that gets the disease started, and we may be able to stop or slow the process if done very early.”Bloom currently is working with colleagues at the UVA School of Medicine to design a clinical trial to investigate the feasibility of using memantine as an early intervention.
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My mother was diagnosed with Altzimers a year ago. Here symptoms were quite alarming hallucinations, anxiety. Now on Mementine all the symptoms have reduced although not a cure it's a big help.
ReplyDeleteReally? Sounds to me like early days on this front but touting it here sure must make the drug companies accountants jump for joy! Now they can sell a very expensive drug to lots more people!! Sorry Im just pretty cynical about drug companies and even the research. Who paid for these studies? The idea of dosing people just in case they might get Alzheimers in the future seems pretty radical.
ReplyDelete"Now they can sell a very expensive drug to lots more people!!"
DeleteHey Hannah, no need to go all conspiracy theorist. Memantadine is dirt cheap: been off patent protection for ages. I've been using Amantadine (similar drug also off-patent) for years to treat what was diagnosed as "Mild Cognative Impairment - likely Alzheimers" for some years. In my case the cause us almost certainly metabolic: it's a kind of diabetes. Type 2 effects muscle tissue; type 3 appears to affect most nerve tissue (& your brain is all nerve tissue). Works a charm, BTW. At least, in combination with dietary mods & a couple of simple supplements. I've rolled back raging peripheral neuropathy and substantial dementia too: got my brain back! So, if your problem is metabolic in origin, there's stuff can be done.
My father was diagnosed with “dementia, probably Alzheimer’s type” in 2008 at age 82. His neurologist placed him on Aricept and Namenda at that time and he remained on it until his death in 2016. In those 8 years he had check ups every 6 months. And though he underwent 3 general anesthesias and the death of my mother, he only lost 3 points- down to 23. He always had trouble with short term memory but had excellent long term memory. He never forgot who his immediate family was as well as his oldest grandchildren. He could always carry on an intelligent conversation and kept his sense of humor. He even started singing which he never did before. I attribute the use of Aricept and Namenda to preserving these parts of his memory and personality, even at his advanced age.
ReplyDeleteHe most likely did not have Alzheimer's, rather, a different form of dementia because his lack of symptoms are not typical for Alzheimer's. Aricept and Namenda do not stop or slow the progression of the disease, they slow the symptoms.
DeleteWhen Phil moved in with me in 1994 there were already signs but I just though they were problems lots of people have, like loosing stuff, forgetting where he put stuff, writing down his reminders; but now I look back and see these were early signs. Maybe a pill taken early would have delayed or even stopped it. Who would have known then.
ReplyDeleteMy mom was diagnosed with vascular dementia and Alzheimer's in 2005. She was immediately put on Aricept and Namenda. Her dementia has finally within the last 6 months really reared its head. About a year ago I asked the doctor if my mom really had dementia as it had never really progressed. She and the nurse both insisted that these two drugs can be very effective in slowing or postponing the emergence of further symptoms. I am going through testing to determine what my own memory problems are. If I'm diagnosed with dementia I plan to start taking these asap. My brother is trying to control his dementia with diet, has never taken these drugs. At the age of 74, my brothers dementia has progressed more this last year than mom's did in 10
ReplyDelete