{"id":2332,"date":"2026-10-05T12:00:25","date_gmt":"2026-10-05T12:00:25","guid":{"rendered":"https:\/\/askneurology.com\/index.php\/2026\/10\/05\/trial-testing-cholesterol-lowering-med-as-potential-alzheimers-intervention\/"},"modified":"2026-10-05T12:00:25","modified_gmt":"2026-10-05T12:00:25","slug":"trial-testing-cholesterol-lowering-med-as-potential-alzheimers-intervention","status":"publish","type":"post","link":"https:\/\/askneurology.com\/index.php\/2026\/10\/05\/trial-testing-cholesterol-lowering-med-as-potential-alzheimers-intervention\/","title":{"rendered":"Trial testing cholesterol-lowering med as potential Alzheimer\u2019s intervention"},"content":{"rendered":"

\"The<\/a><\/p>\n

NewAmsterdam Pharma<\/a> has dosed the first participant in a large mid-stage clinical trial assessing the safety and effectiveness of its cholesterol-lowering treatment candidate obicetrapib<\/a> as a potential aid for people with preclinical Alzheimer\u2019s disease<\/a>.<\/p>\n

The biopharmaceutical company is developing the oral med for individuals at risk of cardiovascular disease who have high levels of low-density lipoprotein, or LDL, the so-called bad cholesterol. Obicetrapib is designed for individuals for whom existing therapies are not well tolerated or effective enough.<\/p>\n

In this new U.S. trial, New Amsterdam is aiming to evaluate whether the therapy could also potentially benefit adults with \u201cbiomarker evidence suggestive of preclinical Alzheimer\u2019s disease who do not have noticeable memory or functional symptoms,\u201d according to a company press release<\/a>. The developer says it\u2019s testing obicetrapib as a possible intervention treatment.<\/p>\n

\u201cThe commencement of this trial is an important step in our effort to understand whether obicetrapib may affect biological changes associated with [Alzheimer\u2019s] before noticeable symptoms develop,\u201d said Michael Davidson, MD, NewAmsterdam\u2019s CEO. Davidson noted that the development of Alzheimer\u2019s \u201ctypically begins years before clinical symptom onset, creating an opportunity for intervention.\u201d<\/p>\n

The Phase 2b SPINOZA study (NCT07794670)<\/a> is enrolling an estimated 400 people ages 55 to 85 at a single site in Nashville, Tennessee<\/a>. Eligible participants will have no evident symptoms but biomarker evidence consistent with early Alzheimer\u2019s.<\/p>\n

\n Recommended Reading<\/span>\n
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\n \"An\n <\/div>\n
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\n Oct. 6, 2023<\/span>
\n\t\t News<\/a><\/span>
\n\t\t by Marisa Horak, MS<\/a><\/span>\n <\/div>\n

<\/a><\/p>\n

Genetic activity analyses show possible therapeutic targets<\/h3>\n

\n <\/p><\/div>\n<\/div>\n<\/div>\n

Alzheimer\u2019s is the most common form of dementia, a group of conditions characterized<\/a> by a decline in memory, thinking, and other cognitive abilities that can affect everyday activities. The disease is marked by the buildup of toxic clumps<\/a> of two proteins, beta-amyloid and tau, which can damage nerve cells. These changes can begin years before symptoms become apparent.<\/p>\n

It\u2019s thought that lipid metabolism \u2014 how the body and brain process cholesterol and other fats \u2014 may also be involved in Alzheimer\u2019s. Certain variants in the APOE<\/em> gene, particularly APOE4<\/em>, increase the risk of developing the disease. This gene provides instructions to produce a protein involved in transporting cholesterol and other fats.<\/p>\n

Obicetrapib aims to lower levels of LDL cholesterol<\/h3>\n

Obicetrapib is a low-dose cholesteryl ester transfer protein (CETP) inhibitor designed to alter cholesterol metabolism. CETP helps move cholesterol between different types of lipoproteins in the bloodstream. By blocking CETP, obicetrapib lowers the levels of LDL cholesterol.<\/p>\n

An earlier Phase 2a trial (NCT05161715)<\/a> sponsored by New Amsterdam explored its effects on brain lipid metabolism in 13 people with early Alzheimer\u2019s carrying at least one copy of the ApoE4<\/em> variant. In that open-label study \u2014 meaning both researchers and participants know the medication being given \u2014 participants received 10 mg of obicetrapib daily for 24 weeks, or about six months.<\/p>\n

The results<\/a> showed reductions in levels of 24- and 27-hydroxycholesterol in the cerebrospinal fluid, the liquid that surrounds the brain and spinal cord. This suggested improved cholesterol metabolism in the brain.<\/p>\n

Participants also experienced an 8% increase in blood beta-amyloid 42\/40 ratio, suggesting less beta-amyloid clumping in the brain. Lower levels of the beta-amyloid 42\/40 ratio have been associated with an increased risk of Alzheimer\u2019s.<\/p>\n

\n Recommended Reading<\/span>\n
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\n \"An\n <\/div>\n
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\n May 3, 2022<\/span>
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\n\t\t by Steve Bryson, PhD<\/a><\/span>\n <\/div>\n

<\/a><\/p>\n

\u2018Good\u2019 Cholesterol in Brain May Aid Cognition, Help Prevent Alzheimer\u2019s<\/h3>\n

\n <\/p><\/div>\n<\/div>\n<\/div>\n

\u2018Growing body of evidence\u2019 links Alzheimer\u2019s and metabolism<\/h3>\n

More recent evidence came from a prespecified analysis of Alzheimer\u2019s biomarkers from a late-stage trial dubbed BROADWAY (NCT05142722)<\/a>. That Phase 3 study, which involved more than 2,500 participants, was originally designed to evaluate obicetrapib for cardiovascular disease rather than Alzheimer\u2019s. The analysis covered 1,535 participants, of whom 367 were APOE4 <\/em>carriers.<\/p>\n

After one year, people treated with obicetrapib had significantly lower increases in blood p-tau217, an early biomarker of Alzheimer\u2019s, compared with those given a placebo. The difference was also significant among APOE4<\/em> carriers. Favorable trends were seen in additional biomarkers, including blood levels of p-tau181 and beta-amyloid 42\/40 ratio.<\/p>\n

\u201cThe findings from our BROADWAY Alzheimer\u2019s disease biomarker analysis, together with the growing body of evidence linking lipid metabolism to Alzheimer\u2019s disease pathology, provide a strong scientific rationale for further evaluating the effect of obicetrapib on biomarkers associated with disease progression and neurodegeneration,\u201d Davidson said.<\/p>\n

Additionally, the findings helped shape SPINOZA\u2019s design. The study is enrolling participants with biomarker evidence consistent with early Alzheimer\u2019s\u00a0who carry two copies of the\u00a0APOE4<\/em>\u00a0variant, two copies of the\u00a0APOE3\u00a0<\/em>variant<\/span>, or one copy of each variant.<\/p>\n

The trial\u2019s participants will be randomly assigned to receive either 10 mg of obicetrapib or a placebo once daily for one year, with treatment groups balanced according to APOE <\/em>genotype, according to New Amsterdam.<\/p>\n

The study\u2019s main goal is to measure changes in blood levels of p-tau217. Secondary outcomes include changes in other Alzheimer\u2019s biomarkers, such as the beta-amyloid 42\/40 ratio, as well as changes in cognitive performance using the Preclinical Alzheimer\u2019s Cognitive Composite 5 (PACC5).<\/p>\n

<\/p>\n

The post Trial testing cholesterol-lowering med as potential Alzheimer\u2019s intervention<\/a> appeared first on Alzheimer’s News Today<\/a>.<\/p>","protected":false},"excerpt":{"rendered":"

NewAmsterdam Pharma has dosed the first participant in a large mid-stage clinical trial assessing the safety and effectiveness of its […]<\/p>\n","protected":false},"author":2,"featured_media":2333,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[25],"tags":[],"class_list":["post-2332","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-alzheimer"],"_links":{"self":[{"href":"https:\/\/askneurology.com\/index.php\/wp-json\/wp\/v2\/posts\/2332","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/askneurology.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/askneurology.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/askneurology.com\/index.php\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/askneurology.com\/index.php\/wp-json\/wp\/v2\/comments?post=2332"}],"version-history":[{"count":0,"href":"https:\/\/askneurology.com\/index.php\/wp-json\/wp\/v2\/posts\/2332\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/askneurology.com\/index.php\/wp-json\/wp\/v2\/media\/2333"}],"wp:attachment":[{"href":"https:\/\/askneurology.com\/index.php\/wp-json\/wp\/v2\/media?parent=2332"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/askneurology.com\/index.php\/wp-json\/wp\/v2\/categories?post=2332"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/askneurology.com\/index.php\/wp-json\/wp\/v2\/tags?post=2332"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}