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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2021-10-26T00:00:00-04:00" class="date-display-single">October 26, 2021</span></p><div class='syndicate'><h1>Common drug may have potential for treating Alzheimer’s disease </h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<ul>
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<li>An FDA-approved drug used for high blood pressure and swelling, called bumetanide, alleviated symptoms of Alzheimer’s disease in mice.</li>
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<li>Electronic health records revealed a lower prevalence of Alzheimer’s disease among people who’d taken the drug.</li>
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<li>The finding suggests that bumetanide warrants further investigation as a possible treatment for Alzheimer’s disease.</li>
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</ul></div><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<picture title="Woman pharmacist taking prescription drugs from shelf">
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2021/20211026-ad.jpg?itok=2pxO0u-7&timestamp=1635190632 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2021/20211026-ad.jpg?itok=x7_vSxtt&timestamp=1635190632 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2021/20211026-ad.jpg?itok=NrZhnxeR&timestamp=1635190632 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2021/20211026-ad.jpg?itok=y8Xsq-se&timestamp=1635190632 1x" media="screen and (min-width: 0)" />
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2021/20211026-ad.jpg?itok=h8DBF6XD&timestamp=1635190632" alt="Woman pharmacist taking prescription drugs from shelf" title="Woman pharmacist taking prescription drugs from shelf" />
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</picture><span class="caption">Researchers have been screening FDA-approved drugs for novel uses. </span><span class="credit">Aleksandar Karanov / Shutterstock</span></div>
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</div><p>Alzheimer’s disease (AD), the leading cause of dementia, has no effective therapies. People with AD differ in their genetic makeup, pathology, and clinical symptoms. This makes traditional drug development for AD difficult. Developing approaches for distinct subpopulations of patients might be a more productive approach.</p>
|
||
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||
<p>The greatest genetic risk factor for late-onset AD occurs in a gene called <em>APOE</em>. Having one copy of a particular form of this gene, called <em>APOE4, </em>increases AD risk by three- to four-fold. Having two copies increases the risk as much as 14-fold.</p>
|
||
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||
<p>A team of researchers led by Drs. Marina Sirota from the University of California, San Francisco, and Yadong Huang from the Gladstone Institutes sought to find a drug that could help patients with AD carrying <em>APOE4</em>. NIH’s National Institute on Aging (NIA) primarily supported the work. Results appeared in <em>Nature Aging</em> on October 11, 2021.</p>
|
||
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||
<p>The team began by comparing gene expression between brain samples from patients with AD and non-AD controls. They identified a set of changes that were unique to people with <em>APOE4. </em>Next, the team looked for existing drugs that might reverse these expression changes. To do so, they consulted a database with information on how more than 1,300 existing drugs affect gene expression.</p>
|
||
|
||
<p>The FDA-approved drug bumetanide stood out as the best candidate for further investigation. Bumetanide is used to treat high blood pressure and swelling caused by heart, liver, or kidney disease. It has also been investigated for brain disorders such as seizures, autism, depression, and schizophrenia. This suggests that it might have effects on the central nervous system that could impact AD.</p>
|
||
|
||
<p>The researchers tested the effects of bumetanide on mouse models of AD with <em>APOE4</em>. These mice have abnormal electrical activity in neurons of the hippocampus, the brain region associated with memory formation. They also have impaired spatial learning. Bumetanide treatment restored normal neuronal activity and reduced spatial learning problems.</p>
|
||
|
||
<p>Beta-amyloid plaques in the brain are one of the hallmarks of AD. In mice with plaques, bumetanide treatment significantly reduced the number of plaques.</p>
|
||
|
||
<p>The researchers confirmed that bumetanide reversed AD-associated gene expression changes in the mice. Bumetanide had a similar effect on gene expression in cultured <em>APOE4</em> human neurons.</p>
|
||
|
||
<p>Finally, the researchers used electronic health records to compare AD prevalence and orders for bumetanide among people over the age of 65. They found a 35-75% lower prevalence of AD in people who were exposed to bumetanide compared with those who weren’t. </p>
|
||
|
||
<p>The results suggest that bumetanide warrants further investigation as an AD treatment. Controlled clinical trials will be needed to confirm the drug’s efficacy in humans.</p>
|
||
|
||
<p>“Our study highlights the power of combining computational drug repurposing with precision medicine,” Huang says. “This may be a really efficient way to find better drugs for Alzheimer’s and other complex age-related diseases.”</p></div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/study-reveals-how-apoe4-gene-may-increase-risk-dementia" target="_top">Study Reveals How APOE4 Gene May Increase Risk for Dementia</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/alzheimers-gene-contributes-blood-brain-barrier-breakdown" target="_top">Alzheimer’s Gene Contributes to Blood-Brain Barrier Breakdown</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/gene-variation-may-protect-against-alzheimers-disease" target="_top">Gene Variation May Protect Against Alzheimer’s Disease</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/clues-alzheimers-disease" target="_top">Clues to Alzheimer’s Disease</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/early-epigenetic-effects-alzheimers-disease" target="_top">Early Epigenetic Effects in Alzheimer’s Disease</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/connecting-small-molecules-genes-disease" target="_top">Connecting Small Molecules, Genes and Disease</a></li><li><a href="https://www.alzheimers.gov" target="_top">Alzheimers.gov</a></li><li><a href="https://medlineplus.gov/druginfo/meds/a684051.html" target="_top">Bumetanide</a></li><li><a href="https://www.nih.gov/about-nih/what-we-do/nih-turning-discovery-into-health/promise-precision-medicine" target="_top">The Promise of Precision Medicine</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="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</a>. Taubes et al, <em>Nature Aging</em>, volume 1, pages 932–947 (2021).</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Institute on Aging (NIA), National Center for Advancing Translational Sciences (NCATS), and National Institute of Environmental Health Sciences (NIEHS).</p>
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