{"id":32606,"date":"2025-12-18T17:48:35","date_gmt":"2025-12-18T17:48:35","guid":{"rendered":"https:\/\/www.tun.com\/home\/?p=32606"},"modified":"2025-12-18T17:48:38","modified_gmt":"2025-12-18T17:48:38","slug":"experimental-drug-nu-9-blocks-early-alzheimers-damage-in-mice","status":"publish","type":"post","link":"https:\/\/www.tun.com\/home\/experimental-drug-nu-9-blocks-early-alzheimers-damage-in-mice\/","title":{"rendered":"Experimental Drug NU-9 Blocks Early Alzheimer\u2019s Damage in Mice"},"content":{"rendered":"\n<div class=\"wp-block-group\"><div class=\"wp-block-group__inner-container is-layout-constrained wp-block-group-is-layout-constrained\">\n<div class=\"wp-block-uagb-blockquote uagb-block-e7eb3fc3 uagb-blockquote__skin-border uagb-blockquote__stack-img-none\"><blockquote class=\"uagb-blockquote\"><div class=\"uagb-blockquote__content\">An experimental Northwestern drug, NU-9, stopped early brain inflammation and toxic protein buildup in an Alzheimer\u2019s mouse model. The work points to a future where people at risk might start treatment long before memory loss begins.<\/div><footer><div class=\"uagb-blockquote__author-wrap uagb-blockquote__author-at-left\"><\/div><\/footer><\/blockquote><\/div>\n\n\n\n<div class=\"wp-block-group is-content-justification-space-between is-nowrap is-layout-flex wp-container-core-group-is-layout-b0ffac9c wp-block-group-is-layout-flex\"><div style=\"font-size:16px\" class=\"has-text-align-left wp-block-post-author\"><div class=\"wp-block-post-author__content\"><p class=\"wp-block-post-author__name\">The University Network<\/p><\/div><\/div>\n\n\n<div class=\"wp-block-uagb-social-share uagb-social-share__outer-wrap uagb-social-share__layout-horizontal uagb-block-ee584a31\">\n<div class=\"wp-block-uagb-social-share-child uagb-ss-repeater uagb-ss__wrapper uagb-block-ec619ce7\"><span class=\"uagb-ss__link\" data-href=\"https:\/\/www.facebook.com\/sharer.php?u=\" tabindex=\"0\" role=\"button\" aria-label=\"facebook\"><span class=\"uagb-ss__source-wrap\"><span class=\"uagb-ss__source-icon\"><svg xmlns=\"https:\/\/www.w3.org\/2000\/svg\" viewBox=\"0 0 512 512\"><path d=\"M504 256C504 119 393 8 256 8S8 119 8 256c0 123.8 90.69 226.4 209.3 245V327.7h-63V256h63v-54.64c0-62.15 37-96.48 93.67-96.48 27.14 0 55.52 4.84 55.52 4.84v61h-31.28c-30.8 0-40.41 19.12-40.41 38.73V256h68.78l-11 71.69h-57.78V501C413.3 482.4 504 379.8 504 256z\"><\/path><\/svg><\/span><\/span><\/span><\/div>\n\n\n\n<div class=\"wp-block-uagb-social-share-child uagb-ss-repeater uagb-ss__wrapper uagb-block-32d99934\"><span class=\"uagb-ss__link\" data-href=\"https:\/\/twitter.com\/share?url=\" tabindex=\"0\" role=\"button\" aria-label=\"twitter\"><span class=\"uagb-ss__source-wrap\"><span class=\"uagb-ss__source-icon\"><svg xmlns=\"https:\/\/www.w3.org\/2000\/svg\" viewBox=\"0 0 512 512\"><path d=\"M389.2 48h70.6L305.6 224.2 487 464H345L233.7 318.6 106.5 464H35.8L200.7 275.5 26.8 48H172.4L272.9 180.9 389.2 48zM364.4 421.8h39.1L151.1 88h-42L364.4 421.8z\"><\/path><\/svg><\/span><\/span><\/span><\/div>\n\n\n\n<div class=\"wp-block-uagb-social-share-child uagb-ss-repeater uagb-ss__wrapper uagb-block-1d136f14\"><span class=\"uagb-ss__link\" data-href=\"https:\/\/www.linkedin.com\/shareArticle?url=\" tabindex=\"0\" role=\"button\" aria-label=\"linkedin\"><span class=\"uagb-ss__source-wrap\"><span class=\"uagb-ss__source-icon\"><svg xmlns=\"https:\/\/www.w3.org\/2000\/svg\" viewBox=\"0 0 448 512\"><path d=\"M416 32H31.9C14.3 32 0 46.5 0 64.3v383.4C0 465.5 14.3 480 31.9 480H416c17.6 0 32-14.5 32-32.3V64.3c0-17.8-14.4-32.3-32-32.3zM135.4 416H69V202.2h66.5V416zm-33.2-243c-21.3 0-38.5-17.3-38.5-38.5S80.9 96 102.2 96c21.2 0 38.5 17.3 38.5 38.5 0 21.3-17.2 38.5-38.5 38.5zm282.1 243h-66.4V312c0-24.8-.5-56.7-34.5-56.7-34.6 0-39.9 27-39.9 54.9V416h-66.4V202.2h63.7v29.2h.9c8.9-16.8 30.6-34.5 62.9-34.5 67.2 0 79.7 44.3 79.7 101.9V416z\"><\/path><\/svg><\/span><\/span><\/span><\/div>\n<\/div>\n<\/div>\n<\/div><\/div>\n\n\n\n<p class=\"wp-block-paragraph\">An experimental drug developed at Northwestern University has halted key early brain changes linked to Alzheimer\u2019s disease in mice, raising hopes for a future treatment that could start years before memory loss and confusion appear.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In a new study, Northwestern researchers used a small-molecule compound called NU-9 in a mouse model of Alzheimer\u2019s disease before the animals showed symptoms. The drug sharply reduced a newly identified, highly toxic form of amyloid beta oligomers \u2014 small clusters of protein fragments \u2014 and calmed early brain inflammation that scientists believe helps drive the disease.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The work, <a href=\"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70968\" target=\"_blank\" rel=\"noopener\" title=\"\">published<\/a> Dec. 18 in Alzheimer\u2019s &amp; Dementia: The Journal of the Alzheimer\u2019s Association, points to a strategy many in the field have long hoped for: intervening at the very beginning of the disease process, not after major damage has already occurred.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The timing of treatment is crucial, according to first author Daniel Kranz, who recently earned his doctorate from Northwestern\u2019s Interdisciplinary Biological Sciences program. He noted that, in Alzheimer\u2019s, harmful changes in the brain build up silently for years.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u201cAlzheimer\u2019s disease begins decades before its symptoms appear, with early events like toxic amyloid beta oligomers accumulating inside neurons and glial cells becoming reactive long before memory loss is apparent,\u201d Kranz said in a news release. \u201cBy the time symptoms emerge, the underlying pathology is already advanced. This is likely a major reason many clinical trials have failed. They start far too late. In our study, we administered NU-9 before symptom onset, modeling this early, pre-symptomatic window.\u201d<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Targeting toxic proteins and inflammation<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Alzheimer\u2019s disease is marked by abnormal clumps and tangles of proteins in the brain, along with chronic inflammation and the gradual loss of neurons and their connections. For decades, researchers have focused on amyloid plaques \u2014 large deposits of amyloid beta protein \u2014 but attention has increasingly shifted to smaller, more mobile clusters called oligomers, which may be more damaging to brain cells.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">In the new study, the Northwestern team discovered that not all amyloid beta oligomers are equally harmful. They identified a previously unknown subtype that appears to be especially toxic and to show up very early in the disease process.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u201cWe identified a distinct amyloid beta oligomer subtype that appears inside neurons and on nearby reactive astrocytes very early in the disease,\u201d Kranz added. \u201cIt potentially acts as an instigator of early Alzheimer\u2019s pathology.\u201d<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Astrocytes are star-shaped support cells that help protect neurons and regulate inflammation. When they become \u201creactive,\u201d they can switch from protective to harmful, releasing inflammatory molecules and contributing to the breakdown of synapses, the communication points between neurons.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The newly identified oligomer subtype, detected by an antibody known as ACU193, first appeared inside stressed neurons in the mouse model. The researchers then saw it move to the surfaces of nearby astrocytes, where it seemed to trigger a wave of inflammation across the brain.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">NU-9, given as a daily oral dose for 60 days to pre-symptomatic mice, dramatically reduced this oligomer subtype. It also significantly lowered reactive astrogliosis \u2014 the inflammatory response of astrocytes \u2014 across multiple brain regions, suggesting a broad anti-inflammatory effect.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u201cThese results are stunning,\u201d added corresponding author William Klein, a professor of neurobiology at Northwestern\u2019s Weinberg College of Arts and Sciences and an expert on Alzheimer\u2019s disease. \u201cNU-9 had an outstanding effect on reactive astrogliosis, which is the essence of neuroinflammation and linked to the early stage of the disease.\u201d<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The drug also reduced an abnormal form of TDP-43, another protein associated with neurodegenerative diseases and cognitive problems, further supporting its potential to protect the brain from early damage.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">A drug with roots in ALS research<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">NU-9 was invented by Northwestern chemist Richard Silverman, best known for discovering pregabalin (Lyrica), a widely used drug for nerve pain, fibromyalgia and epilepsy. About 15 years ago, Silverman set out to design a small molecule that could prevent toxic protein aggregates from building up in neurodegenerative diseases.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">By 2021, NU-9 had shown promise in animal models of amyotrophic lateral sclerosis (ALS), clearing toxic forms of the proteins SOD1 and TDP-43 and restoring the health of upper motor neurons. In 2024, the U.S. Food and Drug Administration cleared NU-9 to begin human clinical trials for ALS.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Earlier this year, Silverman, Klein and Kranz <a href=\"https:\/\/www.pnas.org\/doi\/10.1073\/pnas.2402117122\" target=\"_blank\" rel=\"noopener\" title=\"\">reported<\/a> that NU-9 could also clear toxic amyloid beta oligomers in lab-grown hippocampal neurons, cells from a brain region critical for learning and memory. The new mouse study extends that work into a living brain and focuses on the earliest stages of Alzheimer\u2019s-like disease.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Klein noted that the drug appears to tap into cells\u2019 natural ability to dispose of harmful proteins.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u201cIn both ALS and Alzheimer\u2019s disease, cells suffer from toxic protein buildup,\u201d he added. \u201cCells have a mechanism to get rid of these proteins, but it gets damaged in degenerative diseases like ALS and Alzheimer\u2019s. NU-9 is rescuing the pathway that saves the cell.\u201d<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">A preventive approach, not just treatment<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">The Northwestern team envisions NU-9 not only as a treatment but potentially as a preventive therapy for people who show early biological signs of Alzheimer\u2019s but have not yet developed symptoms.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">That idea mirrors how doctors already manage other chronic diseases, such as heart disease, by treating risk factors before a heart attack or stroke occurs.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u201cMost people are used to monitoring their cholesterol levels,\u201d Silverman said in the news release. \u201cIf you have high cholesterol, it doesn\u2019t mean that you will have a heart attack soon. But it\u2019s time to take drugs to lower your cholesterol levels to prevent that heart attack from happening down the road. NU-9 could play a similar role. If someone has a biomarker signaling Alzheimer\u2019s disease, then they could start taking NU-9 before symptoms appear.\u201d<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Researchers and companies are racing to develop simple blood tests that can detect early signs of Alzheimer\u2019s, such as abnormal amyloid or tau proteins, long before cognitive decline. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Those diagnostics could pair naturally with a drug like NU-9, according to Klein.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u201cThere are a couple early diagnostic blood tests for Alzheimer\u2019s disease in development,\u201d added Klein. \u201cThe promise of better early diagnostics \u2014 combined with a drug that could stop the disease in its tracks \u2014 is the goal.\u201d<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">What comes next<\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">For now, NU-9\u2019s Alzheimer\u2019s results are limited to animal models. Many drugs that look promising in mice ultimately fail in human trials, especially in complex brain diseases. The researchers emphasize that more work is needed to understand exactly how NU-9 works, how early it must be given and whether its benefits last over time.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The team is already testing NU-9 in additional Alzheimer\u2019s models, including one that more closely mimics late-onset disease, the most common form in humans. They plan to follow animals for longer periods to see whether treated mice eventually develop symptoms and to measure how early intervention affects memory and neuron health over time.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">At the same time, NU-9 (also known as AKV9) is moving forward in ALS clinical trials through Akava Therapeutics, the startup Silverman founded to commercialize the compound. Klein is a cofounder of Acumen Pharmaceuticals, which has developed a monoclonal antibody that targets the same toxic amyloid beta oligomer subtype identified in the study.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The new findings do not guarantee that NU-9 will work in people with or at risk for Alzheimer\u2019s. But by revealing a hidden culprit in the earliest stages of the disease and showing that it can be targeted in living brains, the work offers a glimpse of a future where Alzheimer\u2019s might be delayed or even prevented, rather than simply endured.<\/p>\n\n\n\n<div style=\"height:17px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Source: <\/strong><a href=\"https:\/\/news.northwestern.edu\/stories\/2025\/12\/nu-9-halts-alzheimers-disease-in-animal-model-before-symptoms-begin\" target=\"_blank\" rel=\"noopener\" title=\"\">Northwestern University<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>An experimental Northwestern drug, NU-9, stopped early brain inflammation and toxic protein buildup in an Alzheimer\u2019s mouse model. The work points to a future where people at risk might start treatment long before memory loss begins.<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"single-no-separators","format":"standard","meta":{"_acf_changed":false,"_uag_custom_page_level_css":"","_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[25],"tags":[45],"class_list":["post-32606","post","type-post","status-publish","format-standard","hentry","category-science","tag-northwestern-university"],"acf":[],"aioseo_notices":[],"uagb_featured_image_src":{"full":false,"thumbnail":false,"medium":false,"medium_large":false,"large":false,"1536x1536":false,"2048x2048":false},"uagb_author_info":{"display_name":"The University Network","author_link":"https:\/\/www.tun.com\/home\/author\/funky_junkie\/"},"uagb_comment_info":0,"uagb_excerpt":"An experimental Northwestern drug, NU-9, stopped early brain inflammation and toxic protein buildup in an Alzheimer\u2019s mouse model. The work points to a future where people at risk might start treatment long before memory loss begins.","_links":{"self":[{"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/posts\/32606","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/comments?post=32606"}],"version-history":[{"count":10,"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/posts\/32606\/revisions"}],"predecessor-version":[{"id":32658,"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/posts\/32606\/revisions\/32658"}],"wp:attachment":[{"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/media?parent=32606"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/categories?post=32606"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.tun.com\/home\/wp-json\/wp\/v2\/tags?post=32606"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}