Can an Already Approved Drug [bumetanide] Treat Alzheimer’s Disease?

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BrianR
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Can an Already Approved Drug [bumetanide] Treat Alzheimer’s Disease?

Postby BrianR » Mon Oct 11, 2021 12:07 pm

Assuming they can establish a meaningful RCT, it will be interesting to see clinical results in humans.

Article: https://gladstone.org/news/can-already-approved-drug-treat-alzheimers-disease
Researchers at Gladstone Institutes teamed up with scientists from UC San Francisco (UCSF) and Icahn School of Medicine at Mount Sinai and discovered that bumetanide—used for more than 30 years to treat the retention of fluids associated with conditions like hypertension and heart failure—reverses signs of Alzheimer’s disease in mice, as well as in human brain cells. Moreover, when they analyzed electronic health records from two independent institutions, the team discovered that people over 65 who took bumetanide were less likely to develop Alzheimer’s disease than those who didn’t.
...
bumetanide, a diuretic that reduces extra fluid in the body caused by heart failure, liver disease, and kidney disease. Bumetanide is known to work by changing how cells absorb sodium and chloride—both important not only for maintaining appropriate levels of water throughout the body, but also for electrical signaling of neurons in the brain.
...
Based on all these findings, Huang and his colleagues are now planning to work with multiple medical centers to directly move bumetanide toward human clinical trials for treating Alzheimer’s disease, starting with APOE4 carriers.

Based on this paywalled paper:
https://www.nature.com/articles/s43587-021-00122-7
Experimental and real-world evidence supporting the computational repurposing of bumetanide for APOE4-related Alzheimer’s disease
Alice Taubes, Phil Nova, […]Yadong Huang
Nature Aging volume 1, pages 932–947 (2021)
DOI: 10.1038/s43587-021-00122-7

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 (Aβ) 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.

Amykwill
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Re: Can an Already Approved Drug [bumetanide] Treat Alzheimer’s Disease?

Postby Amykwill » Fri Oct 22, 2021 8:12 pm

Is this something that can be used or is it only experimental?
Looks promising

NF52
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Re: Can an Already Approved Drug [bumetanide] Treat Alzheimer’s Disease?

Postby NF52 » Sat Oct 23, 2021 12:45 pm

BrianR wrote: Assuming they can establish a meaningful RCT, it will be interesting to see clinical results...
Amykwill wrote:Is this something that can be used or is it only experimental? Looks promising
Hi "Amy"! Good question! Right now this is in the very early stages of research. The "RCT" BrianR refers to, stands for "randomized controlled trial", which is required before a drug can be approved for a new purpose.

The National Institute on Aging (a division of the NIH) funds most of this research:
Drug Candidates and an excerpt from that website:
One way NIH works to find effective ways to treat dementia is by considering drugs that FDA has already deemed safe for people with other conditions. ....The Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study...is an NIA collaboration with researchers at Harvard Medical School, Rutgers University, and Johns Hopkins University School of Medicine to repurpose FDA-approved drugs for dementia.
The research team recently reported that they discovered a network of about 20 biological pathways linked to abnormal brain metabolism in people with Alzheimer’s and related dementias... the team selected 15 drugs as the best candidates for further analysis... If a drug appears to reduce the risk or severity of Alzheimer’s or a related dementia, researchers could conduct lab tests to determine how the drug works against dementia, and the drugs could eventually be tested with people in clinical trials.
Here's another recent forum discussion on the Bumetanide study:
Bumetanide for APOE4 Carriers

As an aside--I noticed in your first post that you are interested in studies. Here's an online study that you might want to try out APT webstudy
(Hint: be sure to watch the tutorial videos in the FAQ section to see how these "card games" work!) I've done this every three months for a year now, and have to say it's a fun challenge and rewarding to see my cognition as a 69-year old ApoE 4/4 woman is still fine.

Don't despair, Amy--you only have 50% of your mom's genes. I inherited an ApoE 4 from each parent, but didn't get my mom's hypothyroidism, osteoporosis, high blood pressure, or anemia. I didn't get my dad's Type2 diabetes or early coronary artery disease (or baldness, thank goodness!) The science is moving incredibly fast on both lifestyle strategies for prevention and therapies for prevention and intervention. Enjoy having those adult children and look at this news as a way of meeting new friends in a new school (the ApoE 4 school of life-long learning!)
4/4 and still an optimist!

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Re: Can an Already Approved Drug [bumetanide] Treat Alzheimer’s Disease?

Postby Amykwill » Sat Oct 23, 2021 12:54 pm

Thanks so much BrianR! I love your optimism and want to get to that point myself. I will definitely check out that study. I really appreciate your feedback and personal story :)

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Re: Can an Already Approved Drug [bumetanide] Treat Alzheimer’s Disease?

Postby NF52 » Sat Oct 23, 2021 1:07 pm

Amykwill wrote:Thanks so much BrianR! I love your optimism and want to get to that point myself. I will definitely check out that study. I really appreciate your feedback and personal story :)
Hi Amy,
Thanks for your kind words!
Brian is a great, smart guy--but I think he's a good bit younger than this grandmother of two! I used the quotation mark in the upper right to be sure he saw your question and my reply. We have a free forum software that makes all of us learn new skills! ;)
NF52
4/4 and still an optimist!

BrianR
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Re: Can an Already Approved Drug [bumetanide] Treat Alzheimer’s Disease?

Postby BrianR » Fri Nov 12, 2021 4:58 pm

NF52 wrote:Brian is a great, smart guy--but I think he's a good bit younger than this grandmother of two!

NF52, your assessment is very generous :) As for the age thing, well my younger brother is a grandfather of three. But at least I still have a few months before I need to sign up for Medicare ...

(And I also love your optimism and consistently outstanding answers.)


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