{"id":13976,"date":"2025-04-14T10:00:00","date_gmt":"2025-04-14T10:00:00","guid":{"rendered":"https:\/\/modernsciences.org\/staging\/4414\/?p=13976"},"modified":"2025-04-03T10:36:48","modified_gmt":"2025-04-03T10:36:48","slug":"early-onset-alzheimers-drug-trial-amyloid-therapy-cognitive-decline-april-2025","status":"publish","type":"post","link":"https:\/\/modernsciences.org\/staging\/4414\/early-onset-alzheimers-drug-trial-amyloid-therapy-cognitive-decline-april-2025\/","title":{"rendered":"Early-onset Alzheimer\u2019s: new drug shows promise in slowing the disease"},"content":{"rendered":"\n\n
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\n The drug also caused a notable decrease in amyloid plaque buildup, which is a hallmark of Alzheimer\u2019s disease.\n ART-ur\/ Shutterstock<\/a><\/span>\n <\/figcaption>\n <\/figure>\n\n Rahul Sidhu<\/a>, University of Sheffield<\/a><\/em><\/span>\n\n

Alzheimer\u2019s disease is usually associated with old age. But around 5%-10% of all Alzheimer\u2019s cases<\/a> occur in people under the age of 65. Early-onset Alzheimer\u2019s disease<\/a> progresses more rapidly and often strikes people in the prime of their lives. Treatment options remain limited.<\/p>\n\n

But new data from a recent clinical trial<\/a> suggests that a previously discontinued experimental drug, called gantenerumab, could help. The study found that gantenerumab reduced the buildup of amyloid plaques \u2013 one of the hallmarks of Alzheimer\u2019s disease \u2013 in the brain. This may help slow cognitive decline in people with early-onset Alzheimer\u2019s.<\/p>\n\n

Early-onset Alzheimer\u2019s is often linked to genetic mutations<\/a> in three specific genes. These mutations cause the brain to produce excessive amounts of amyloid beta, a protein that clumps together to form plaques. These plaques disrupt brain function, leading to memory loss.<\/p>\n\n

Early-onset Alzheimer\u2019s advances quickly \u2013 and the rapid decline is devastating. That\u2019s why researchers are racing to find treatments that can slow the disease.<\/p>\n\n\n\n

The recent clinical trial was a randomised, placebo-controlled study to evaluate gantenerumab\u2019s effects on people with early-onset Alzheimer\u2019s. Researchers monitored changes in the participants\u2019 cognitive abilities, and also used brain imaging and blood biomarkers (the presence of specific proteins in the blood which are linked to Alzheimer\u2019s), to track the disease\u2019s progress throughout the study.<\/p>\n\n

The trial included 73 participants with rare inherited genetic mutations known to cause early-onset Alzheimer\u2019s. These participants were either asymptomatic or had mild Alzheimer\u2019s symptoms at the start of the study. <\/p>\n\n

The results were intriguing. In a subgroup of 22 participants, who hadn\u2019t had any cognitive issues at the start of the study, taking the treatment for an average of eight years reduced the risk of developing symptoms from a nearly 100% likelihood, to 50%. Brain scans also showed a notable decrease in amyloid buildup.<\/p>\n\n

Immune defenders<\/h2>\n\n

Gantenerumab<\/a> is a monoclonal antibody \u2013 a lab-engineered protein designed to attach to amyloid beta in the brain. By binding to these plaques, it signals the immune system to clear them away. This may potentially slow Alzheimer\u2019s progression.<\/p>\n\n

The drug works by engaging microglial cells<\/a>. These are the brain\u2019s primary immune defenders. Microglia constantly monitor the brain for damage and remove harmful substances, including amyloid beta. However, in people with Alzheimer\u2019s disease, microglia often fail to clear plaques efficiently<\/a>. Gantenerumab enhances this natural defence mechanism by tagging amyloid plaques, making them easier for the microglia to recognise and break down.<\/p>\n\n

\n \"A\n
\n Microglia cells fail to clear plaques effectively in people with Alzheimer\u2019s.<\/span>\n ART-ur\/ Shutterstock<\/a><\/span>\n <\/figcaption>\n <\/figure>\n\n

Amyloid beta is thought to play a central role in Alzheimer\u2019s by triggering inflammation, interfering with cell communication and ultimately killing neurons. By removing these plaques, gantenerumab may help to protect brain function. However, it doesn\u2019t reverse existing damage \u2013 which is why early intervention is critical.<\/p>\n\n

An advantage of gantenerumab is that it can cross the blood-brain barrier<\/a> \u2013 the protective shield that blocks many drugs and harmful substances from reaching the brain. This allows it to act directly on amyloid plaques, making it more effective than some earlier treatments that struggled with drug delivery<\/a>.<\/p>\n\n

But as promising as these results are, gantenerumab isn\u2019t without risks. <\/p>\n\n

A major concern is amyloid-related imaging abnormalities<\/a>. These are swelling or small spots of bleeding in the brain that show up on MRI scans. This is a common side-effect of amyloid-targeting therapies. <\/p>\n\n

In this latest trial, 53% of participants experienced these amyloid-related imaging abnormalities, including small brain bleeds in 27% of participants, brain swelling in 30% of participants and iron deposits from bleeding in 6%. While no participants had major brain haemorrhages or died from the treatment, these side-effects remain a serious concern \u2013 requiring regular monitoring through brain scans.<\/p>\n\n

Another limitation is the modest cognitive benefit observed in the trial. While gantenerumab reduced amyloid plaques, the extent to which this translates into meaningful improvements in memory and thinking skills remains unclear. <\/p>\n\n

Gantenerumab is also expensive to manufacture, which could make widespread access difficult if it gains regulatory approval. As this is an experimental drug, we do not currently know how much it would cost. But other similar anti-amyloid therapies, such as donanemab, currently cost around \u00a325,000 per patient per year<\/a>.<\/p>\n\n

The study also had a small sample size and only focused on a rare genetic form of early-onset Alzheimer\u2019s. More research is needed to see how these results may apply to the wider dementia community.<\/p>\n\n

The future of treatment<\/h2>\n\n

Although the trial was terminated early after the study\u2019s sponsor pulled out, these findings contribute to the ongoing debate over the causes of Alzheimer\u2019s disease.<\/p>\n\n

According to the amyloid hypothesis, the buildup of amyloid plaques in the brain is the main cause of Alzheimer\u2019s disease. Clearing these plaques will slow the disease\u2019s progression. The success of the Alzheimer\u2019s drugs lecanemab<\/a>, donanemab<\/a> and now gantenerumab, lend themselves to this theory.<\/p>\n\n

This study also underscores the importance of early diagnosis. Amyloid-targeting therapies appear to work best in the early stages of Alzheimer\u2019s, before significant brain damage occurs<\/a>. Advances in biomarker testing \u2013 including blood tests<\/a> and brain scans \u2013 could help identify at-risk people sooner. This would improve the effectiveness of drugs such as gantenerumab.<\/p>\n\n

Although gantenerumab is not a cure and was discontinued<\/a> by its manufacturer in 2022 because it failed to demonstrate efficacy in slowing the progression of Alzheimer\u2019s disease, this new data could perhaps lead to gantenerumab being manufactured again. It also represents another step forward in the fight against Alzheimer\u2019s. <\/p>\n\n

Alzheimer\u2019s research is advancing faster than ever before. Whether a success or a setback, each new study adds to our understanding of the disease and brings us closer to more effective treatments. For now, the gantenerumab trial offers a hopeful sign that scientists are making progress in slowing the course of this devastating condition.\"The<\/p>\n\n

Rahul Sidhu<\/a>, PhD Candidate, Neuroscience, University of Sheffield<\/a><\/em><\/span><\/p>\n\n

This article is republished from The Conversation<\/a> under a Creative Commons license. Read the original article<\/a>.<\/p>\n<\/div>\n\n","protected":false},"excerpt":{"rendered":"The drug also caused a notable decrease in amyloid plaque buildup, which is a hallmark of Alzheimer\u2019s disease.…\n","protected":false},"author":1135,"featured_media":13978,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"nf_dc_page":"","fifu_image_url":"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/d\/d0\/The_Glowing_Emptiness_of_an_Alzheimer%27s_Disease_Patient.jpg","fifu_image_alt":"","footnotes":""},"categories":[12],"tags":[7218,7223,7229,7231,7225,7230,7228,7227,7224,7221,7216,7226,7222,7234,7220,7233,7217,7232,7235,7219],"class_list":{"0":"post-13976","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health-and-body","8":"tag-alzheimers-biomarkers","9":"tag-alzheimers-clinical-trials","10":"tag-alzheimers-disease-research","11":"tag-alzheimers-drug-development","12":"tag-alzheimers-early-diagnosis","13":"tag-amyloid-hypothesis","14":"tag-amyloid-plaques-and-alzheimers","15":"tag-amyloid-related-imaging-abnormalities","16":"tag-amyloid-targeting-therapies","17":"tag-blood-brain-barrier-and-drug-delivery","18":"tag-brain-imaging-in-alzheimers","19":"tag-cognitive-decline-prevention","20":"tag-dementia-treatment-advancements","21":"tag-early-onset-alzheimers","22":"tag-experimental-alzheimers-treatments","23":"tag-gantenerumab-trial","24":"tag-genetic-mutations-and-alzheimers","25":"tag-microglia-and-brain-immunity","26":"tag-monoclonal-antibody-treatment","27":"tag-neuroinflammation-in-alzheimers","28":"cs-entry","29":"cs-video-wrap"},"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/posts\/13976","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/users\/1135"}],"replies":[{"embeddable":true,"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/comments?post=13976"}],"version-history":[{"count":1,"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/posts\/13976\/revisions"}],"predecessor-version":[{"id":13977,"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/posts\/13976\/revisions\/13977"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/media\/13978"}],"wp:attachment":[{"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/media?parent=13976"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/categories?post=13976"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/modernsciences.org\/staging\/4414\/wp-json\/wp\/v2\/tags?post=13976"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}