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 ? (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
= new reply since forum marked as read
Alzheimer's "vaccine", now with 6G signal..... 
