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Wed Oct 13, 2021, 10:12 AM

Repurposed Drug Reverses Signs of Alzheimer's in Mice, Human Cells

umetanide, a drug already approved to treat swelling associated with conditions such as heart failure, improved performance on cognitive tests and reduced the buildup of amyloid plaques in mice with an Alzheimer’s-like condition, researchers report. Furthermore, in cultured human neurons derived from stem cells, bumetanide reversed gene expression changes associated with Alzheimer’s, and the electronic health records of millions of patients point to a link between the drug and reduced odds of being diagnosed with the disease.

On the basis of these results, published this week (October 10) in Nature Aging, Gladstone Institutes neurobiologist and study coauthor Yadong Huang tells STAT that he and his team are now pursuing a clinical trial to test the drug in human patients with at least one copy of the APOE4 variant, a well-known risk factor for the disease.

Bumetanide blocks ion channels in the cell membrane, thereby altering salt balances and reducing water retention, but how this mechanism might affect neural function is not known. “The mechanism of the drug is well-known, but what the authors haven’t addressed is how that mechanism is related to what they think might happen if they were to give this drug to Alzheimer’s patients,” Johns Hopkins University neurologist Shilpa Kadam, who was not involved in the study, tells STAT.

https://www.the-scientist.com/news-opinion/repurposed-drug-reverses-signs-of-alzheimer-s-in-mice-human-cells-69305


Experimental and real-world evidence supporting the computational repurposing of bumetanide for APOE4-related Alzheimer’s disease

Abstract

The evident genetic, pathological and clinical heterogeneity of Alzheimer’s disease (AD) poses challenges for traditional drug development. We conducted a computational drug-repurposing screen for drugs to treat apolipoprotein E4 (APOE4)-related AD. We first established APOE genotype-dependent transcriptomic signatures of AD by analyzing publicly available human brain databases. We then queried these signatures against the Connectivity Map database, which contains transcriptomic perturbations of more than 1,300 drugs, to identify those that best reverse APOE genotype-specific AD signatures. Bumetanide was identified as a top drug for APOE4-related AD. Treatment of APOE4-knock-in mice without or with amyloid β (A? accumulation using bumetanide rescued electrophysiological, pathological or cognitive deficits. Single-nucleus RNA sequencing revealed transcriptomic reversal of AD signatures in specific cell types in these mice, a finding confirmed in APOE4 induced pluripotent stem cell (iPSC)-derived neurons. In humans, bumetanide exposure was associated with a significantly lower AD prevalence in individuals over the age of 65 years in two electronic health record databases, suggesting the effectiveness of bumetanide in preventing AD.

https://www.nature.com/articles/s43587-021-00122-7

14 replies, 2523 views

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Response to Klaralven (Original post)

Wed Oct 13, 2021, 10:17 AM

1. Hope they find it works. For now it's relatively cheap around $30 a month

without insurance.

We aren't mice and these studies and peer review takes time.

Fingers crossed.

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Response to mucifer (Reply #1)

Wed Oct 13, 2021, 10:21 AM

2. The review of databases of people already taking bumetanide for other reasons seems more significant

As we have access to more and more digital health records, we should be mining them for associations between existing drugs and the prevention of various off-target diseases.

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Response to Klaralven (Original post)

Wed Oct 13, 2021, 10:23 AM

3. and this is why it was so smart that they insisted on implementing emr's to the aca.

one of many really important things in that law that nobody knows about.
this has the potential to refine both best meds and best practices throughout medicine.
this is an eye on the whole system. this is 21st century medicine.

my other favorite is making hospitals open their records on prices, but also things like errors.
gonna make it a lot easier to catch the cheats.

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Response to mopinko (Reply #3)

Wed Oct 13, 2021, 11:44 AM

6. I'd also like to see the EMRs used to measure comparative efficacy of drugs

Especially to compare the efficacy of new, patented, expensive drugs versus generics.

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Response to Klaralven (Reply #6)

Wed Oct 13, 2021, 11:57 AM

8. i'm sure it will.

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Response to Klaralven (Original post)

Wed Oct 13, 2021, 10:23 AM

4. I think that is someone could read that OP cold with no trips or errors, it might be a good ...

... test for Alzheimers.

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Response to Klaralven (Original post)

Wed Oct 13, 2021, 11:06 AM

5. Better circulation reduces swelling, no surprise.

What took them so long to test this? How long has this med been ambient?

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Response to Klaralven (Original post)

Wed Oct 13, 2021, 11:47 AM

7. KnR

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Response to Klaralven (Original post)

Wed Oct 13, 2021, 11:59 AM

9. Bah, humbug...

These researchers are employed by educational institutions and big pharma! Surely there is a conspiracy there somewhere! I heard ivermectin cures Alzheimer's!

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Response to Klaralven (Original post)

Wed Oct 13, 2021, 12:17 PM

10. Tears of joy. It comes too late for my sister... she's just about 10 years older than me...

... and she doesn't remember me any more. She'll look at the person talking, but she doesn't speak or show emotion. What an insidious thing Alzheimer's disease is. Heartbreaking. Every time I forget a name or lose my keys or can't find where I parked, I wonder... "is it starting? Has it already started? Is it progressing?"

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Response to NurseJackie (Reply #10)

Wed Oct 13, 2021, 12:42 PM

11. Was you sister taking medications in the early stages?

My husband has been on Donepezil and Namenda for at least 8 years. The disease is progressing, but very slowly. He lives in the moment.

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Response to SleeplessinSoCal (Reply #11)

Wed Oct 13, 2021, 12:50 PM

12. Namenda... but it still progressed. Somewhat slower, but considering the side effects...

... her family and doctor discontinued it about 4-5 years ago. She understood why she was taking it and what was going to happen eventually. Although she was no longer making her own medical decisions, she agreed.


For others who may want to read-along: https://www.rxlist.com/namenda-side-effects-drug-center.htm

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Response to Klaralven (Original post)

Wed Oct 13, 2021, 04:37 PM

13. Great news!

I wish they would use this data base to look at a lot of other drugs, especially statins, and links to them causing problems in systems that are not part of the drug target. Physicians seem blind to unintended effects of medications. Maybe because so many of them have a "gift" relationship with pharmaceutical reps and companies.

I didn't know that the ACA helped to create this database, so thanks for that information.

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Response to Klaralven (Original post)

Wed Oct 13, 2021, 04:52 PM

14. Yeah right! Don't believe it people. They're just trying to get us all on this

Alzheimer's "vaccine", now with 6G signal.....

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