Posted on 10/14/2021 12:35:51 PM PDT by Red Badger
Researchers on the hunt for a pre-approved medicine that can be repurposed to treat Alzheimer’s disease have found promising signs of effectiveness in a 50-year-old generic drug commonly used as a diuretic. Through a variety of animal studies and real-world investigations, the new study indicates exposure to the common drug could significantly reduce a person’s risk of developing Alzheimer’s.
Researchers on the hunt for a pre-approved medicine that can be repurposed to treat Alzheimer’s disease have found exposure to a common diuretic drug could significantly reduce a person’s risk of developing Alzheimer’s.
The research began several years ago with the study of brain tissue samples from deceased Alzheimer’s patients. A novel computational approach was devised to identify gene expression profiles unique to the disease and the researchers quickly focused on specific variants associated with a gene called APOE, previously known to confer heightened risk of Alzheimer’s.
The work then shifted to analyzing a database of over 1,300 FDA-approved medicines. The goal was to home in on any drug that could switch those genes back to a healthy profile.
"This unbiased approach allowed us to find which drugs might be able to flip the altered gene expression associated with APOE4-related Alzheimer's disease back to the normal state," explains lead author Alice Taubes. "It gave us important clues in solving the puzzle of which drugs could be effective against APOE4-related Alzheimer's disease."
Emerging as the top candidate was a drug called bumetanide. It has been used for several decades, primarily as a diuretic.
The researchers then conducted a series of experiments testing the drug’s effect on multiple animal models of Alzheimer’s disease. The results were promising, with the drug reducing cognitive or memory deficits as well as cutting the volume of toxic amyloid proteins and restoring normal electrical brain activity.
"In traditional drug development, in addition to animal and cell studies, we would typically need to do in-depth safety testing before launching clinical trials in humans," notes Marina Sirota, co-senior author of the study. "But with an existing FDA-approved drug, we can leverage the real-world human data to test, in silico, what the drug might be able to achieve."
So the researchers looked to real-world data to get an idea of the drug’s effectiveness at preventing Alzheimer’s disease in humans. Electronic health records from more than five million people were analyzed and whittled down to two age and demographically matched groups of around 3,000 people each – one group exposed to bumetanide and the other exposed to a different kind of diuretic.
Even though both groups shared similar genetic risks of developing Alzheimer’s disease, the people exposed to bumetanide were 35 to 75 percent less likely to be diagnosed with the disease. Yadong Huang, senior author on the study, says although the animal studies with bumetanide focused on a specific APOE4 genetic predisposition to Alzheimer’s, the real-world investigations were more general, indicating bumetanide could be broadly effective.
"Since the two electronic health record databases do not separate patients according to their APOE versions, these real-world data suggest that bumetanide might work more broadly against Alzheimer's disease, beyond the patients who carry two copies of APOE4," says Huang.
These findings are not the first time bumetanide has been proposed to treat neurological disorders. The mechanism by which the drug treats water retention in cells also influences neuron activity.
For several years bumetanide was considered a promising therapeutic for autism spectrum disorder. Animal studies and initial human trials showed the drug could potentially reduce behavioral abnormalities linked to the condition. However, those hopes recently started to dissipate after a pair of large Phase 3 trials were discontinued following interim analyses suggesting it was no better than placebo.
Jeffrey Cummings, a neuroscientist from the University of Nevada Las Vegas, who did not work on this new study, is unconvinced these findings mean bumetanide will directly work as an effective Alzheimer’s treatment. He says it is more likely these findings will help point researchers in new directions to develop drugs based on how bumetanide could be improving the condition.
“This drug’s relationship to Alzheimer’s disease is not quite proven and its side effect profile is undesirable in older people,” says Cummings in an interview with StatNews. “I would see this much more as pointing us toward a repertoire of pathways that have not been adequately investigated.”
Because bumetanide is already approved by the FDA with an established safety profile the researchers are swiftly moving to begin a large-scale clinical trial testing its efficacy. The initial trial will concentrate on patients with specific APOE4 genetic risk factors.
Jean Yuan, the drug development program director in the National Institute on Aging’s (NIA) Division of Neuroscience, says the study’s findings are strong enough to prompt a clinical trial testing bumetanide in people with certain genetic risk factors for Alzheimer’s. However, she points out it is probable the future of Alzheimer’s treatments will be highly personalized, as it is becoming increasingly likely the disease is much more heterogenous that previously thought.
“We know that Alzheimer’s disease will likely require specific types of treatments, perhaps multiple therapies, including some that may target an individual’s unique genetic and disease characteristics — much like cancer treatments that are available today,” says Yuan.
The new research was published in the journal Nature Aging.
Source: NIH/Gladstone Institutes
Zhang L, Huang CC, Dai Y, Luo Q, Ji Y, Wang K, et al. (January 2020). “Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios”. Translational Psychiatry. 10 (1): 9.
Wonder if Alzheimer’s disease share some sort of connection with autism? The past few years people have been experimenting with diuretics for autism and now for Alzheimer’s.
So that is what Biden is taking.
“We know that Alzheimer’s disease will likely require specific types of treatments, perhaps multiple therapies, including some that may target an individual’s unique genetic and disease characteristics — much like cancer treatments that are available today,” says Yuan.
Alzheimer's was discovered in 1907, and to date there is no prevention, treatment or cure for it.
Any meaningful break throughs appears to be many more decades way. - Tom
There may be numerous causes for this disease and that would call for numerous treatments as well.................
About 4 years ago, I was diagnosed with CHF, and my cardio doc put me on Lasix as my diuretic.
Lasix got its name for lasting six hours. That meant that you were peeing for 6 hours at least off and on.
My RN wife got my Cardio doc to write an RX for Bumex 2mg.
Bumex makes you pee like a race horse for about 3 hours and 1 more before it therapeutic action is gone.
I’m down to one half of a 1 mg Bumex tablet/day 6 days a week.(One day of rest for my kidney’s and bladder)
BP wise, my BP is now normal, and I have lost the 5-6 pounds of weight I had gained. My shortness of breath is basically gone.
Now, Bumex may help my aging memory.
There may be numerous causes for this disease and that would call for numerous treatments as well.
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True that. Amyloid is simply the resulting collection of dead nerve cells. I’d like to see more research done into apoptosis due to glyceraldehyde.
Every day in my own personal battle with the medical community I am in awe of the research scientists and have mostly disdain for the Drs who dont have a clue.
I have a scientific blood test developed for a reason that has been giving the red flag to every DR..and EVERY Dr has had no clue how to deal with it
I credit that test and scientists for saving my life because it gave me the strength to battle when everyone was clueless.
Oh...and btw, those basic function blood tests that look oh so normal...don’t mean everything is fine in your body...and I am going to throw it in the face of every clueless Dr in my next visit...in a nice way...of course
I don’t know what purpuric halos look like with cherry angiomas but they can be a sign of that disorder
talking about amyloidosis
Bumex is just a high priced Lasix. I don’t know about preventing Alzheimer’s, but it will sure put you in a diaper quick.
bumetanide? Hmmm..
Like checking the oil in your car is fine but the brakes are bad...................
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