{"id":17080,"date":"2022-01-11T12:08:53","date_gmt":"2022-01-11T12:08:53","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/blog\/alzheimers-disease-and-neurodegeneration-a-brighter-outlook\/"},"modified":"2022-01-11T12:08:53","modified_gmt":"2022-01-11T12:08:53","slug":"alzheimers-disease-and-neurodegeneration-a-brighter-outlook","status":"publish","type":"blog","link":"https:\/\/www.sygnaturediscovery.com\/fr\/blog\/alzheimers-disease-and-neurodegeneration-a-brighter-outlook\/","title":{"rendered":"Alzheimer\u2019s disease and neurodegeneration: A brighter outlook?"},"content":{"rendered":"

Alzheimer\u2019s disease (AD) is a devastating disease for the patient, their family and friends, and also their community and wider society. The \u03b2-amyloid (A\u03b2) hypothesis of AD proposes that this protein is deposited in the brain up to 20 years before symptoms become apparent. These deposits show as plaques or clumps in the brain and are a neuropathological hallmark of AD.<\/strong><\/span><\/p>\n

\"Alzheimer's<\/p>\n

\u00a0<\/p>\n

\u03b2-amyloid is thought to trigger a cascade of events in the brain, including a mass of twisted proteins inside nerve cells (neurofibrillary tangles) that occur because of an increase in the activity levels of a protein called tau (i.e. hyperphosphorylation).<\/span><\/p>\n

This leads to the loss of nerve cells in the brain and neuroinflammation. It\u2019s thought that neurofibrillary tangles and tau hyperphosphorylation lead to cognitive decline and other symptoms of AD.<\/span><\/p>\n

The A\u03b2 hypothesis has driven a major effort by the pharmaceutical industry to develop drugs that reduce \u03b2-amyloid levels in the brain to prevent the downstream events and alleviate the symptoms of AD.<\/span><\/p>\n

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\"Illustration<\/h3>\n

The first drug approval in two decades<\/strong><\/h2>\n

Up until 2021 the only medicines available for AD patients were donepezil, galantamine, rivastigmine and memantine. All these drugs treat the symptoms of AD, but do not alter the progress of the disease.<\/span><\/p>\n

After a nearly two-decade wait, a new drug has been approved for AD by the FDA \u2013 based on the A\u03b2 hypothesis.<\/span><\/p>\n

Biogen\u2019s aducanumab (Aduhelm) is a monoclonal antibody drug that clearly reduces\/removes A\u03b2 in the brains of AD patients with mild\/moderate symptoms in two PIII trials.<\/span><\/p>\n

What\u2019s less certain is whether aducanumab provides convincing evidence of clinical benefit \u2013 that is, cognitive improvement.<\/span><\/p>\n

The controversy that has erupted around the approval of aducanumab has been covered extensively by expert scientific and non-scientific literature.<\/span><\/p>\n

Outside the specific details of the two PIII trials with aducanumab, the broader question that has arisen is why previous drugs that also reduce brain A\u03b2 levels in AD have not been approved by the FDA; it\u2019s worth noting that the European Medicines Agency has recently decided not to approve aducanumab.<\/span><\/p>\n

\u00a0<\/p>\n

\"\"<\/p>\n

Is aducanumab different? <\/strong><\/h2>\n

Aducanumab is the not the first or only monoclonal antibody drug targeting A\u03b2 to have been assessed in the clinic or in development.<\/span><\/p>\n

Previous drugs have failed in pivotal PIII trials, including bapineuzumab, solanezumab, crenezumab and gantenerumab, despite evidence of reduced A\u03b2 levels. Other monoclonal antibodies drugs are still in development, including donanemab, locanemab and BAN-2401.<\/span><\/p>\n

There are multiple inter-related scientific and non-scientific reasons why some monoclonal antibody drugs have stalled in development while others are still progressing.<\/span><\/p>\n

These include inadequate doses tested, levels of target engagement, levels of A\u03b2 lowering, effects on phosphorylated-tau, impacts on broad biomarkers of neurodegeneration, differential pharmacokinetics and brain penetration, benefit-risk considerations, routes and frequencies of administration\/compliance, futility analysis of clinical trials, and strategic reasons.<\/span><\/p>\n

One area of biology that\u2019s of growing interest is the selectivity of monoclonal antibodies for different species of A\u03b2.<\/span><\/p>\n

There are soluble A\u03b2 species (monomers and oligomers of different length) and insoluble species (fibrils and plaques), with current evidence suggesting that soluble oligomers are key to neurodegeneration and disease progression in AD.<\/span><\/p>\n

Is this part of the reason why drugs like bapineuzumab, which targets all species of A\u03b2, and solanezumab, which targets monomers, have not progressed?<\/span><\/p>\n

If so, then the development of monoclonal antibodies BAN-2401 and PMN201 that show higher selectivity for soluble oligomers than plaques compared to aducanumab, bapineuzumab or gantenerumab are of key interest.<\/span><\/p>\n

Likewise, the small molecule drug ALZ-801 prevents the formation of A\u03b2 oligomers from monomers with no affinity for plaques, and there are other efforts aimed at more specifically targeting soluble A\u03b2 oligomers.<\/span><\/p>\n

These are exciting times for Alzheimer\u2019s disease drug discovery.<\/span><\/p>\n

\u00a0<\/p>\n

\u00a0<\/p>\n

\"The<\/p>\n

\u00a0<\/p>\n

Leaps forward for Alzheimer\u2019s disease drug discovery<\/strong><\/h2>\n

Despite the failures and controversies, the science of AD and neurodegenerative disorders (NDDs) more broadly has come a long way<\/a>.<\/span><\/p>\n

We now understand more about neurodegenerative disease mechanisms at the molecular and cellular level.<\/span><\/p>\n

NDDs as a group are considered proteinopathies, with aberrant production or processing of proteins such as A\u03b2, \u03b1-synuclein, tau, TDP-43, FET, PrP, Htt variously driving brain pathology and ultimately symptoms in AD, Parkinson\u2019s disease, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear pals, Huntington\u2019s disease and other NDDs.<\/span><\/p>\n

All these proteinopathies lead to protein aggregation and accumulation in the brain, and as with A\u03b2 in AD, there are therapeutic approaches targeting removal\/reduction of these aberrant proteins in different NDDs.<\/span><\/p>\n

However, these different proteinopathies also have similar detrimental effects on cellular mechanisms and processes. These include engendering energy deficiency, impairment of detoxification mechanisms leading to cell and DNA damage, overwhelming protein homeostasis mechanisms, inflammation in the brain, overactivity of cells, and cell death.<\/span><\/p>\n

Today, there are multiple R&D efforts focused on correcting these common cellular dysfunctions from a disease-agnostic perspective \u2013 bringing hope that novel therapeutics might be effective across multiple NDDs despite differing protein aetiologies.<\/span><\/p>\n

\u00a0<\/p>\n

Visit our Neuroscience page to find out more about how we can help your project<\/strong><\/a><\/h3>\n","protected":false},"excerpt":{"rendered":"","protected":false},"featured_media":17081,"template":"","category":[29],"class_list":["post-17080","blog","type-blog","status-publish","has-post-thumbnail","hentry","category-non-categorise"],"acf":[],"yoast_head":"\nAlzheimer\u2019s disease and neurodegeneration: A brighter outlook? - Sygnature<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.sygnaturediscovery.com\/fr\/blog\/alzheimers-disease-and-neurodegeneration-a-brighter-outlook\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Alzheimer\u2019s disease and neurodegeneration: A brighter outlook? - Sygnature\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.sygnaturediscovery.com\/fr\/blog\/alzheimers-disease-and-neurodegeneration-a-brighter-outlook\/\" \/>\n<meta property=\"og:site_name\" content=\"Sygnature\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2026\/02\/sygnature-hit-to-lead-team-collaboration-scaled.webp\" \/>\n\t<meta property=\"og:image:width\" content=\"2560\" \/>\n\t<meta property=\"og:image:height\" content=\"1707\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/webp\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Estimation du temps de lecture\" \/>\n\t<meta name=\"twitter:data1\" content=\"4 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/blog\\\/alzheimers-disease-and-neurodegeneration-a-brighter-outlook\\\/\",\"url\":\"https:\\\/\\\/www.sygnaturediscovery.com\\\/fr\\\/blog\\\/alzheimers-disease-and-neurodegeneration-a-brighter-outlook\\\/\",\"name\":\"Alzheimer\u2019s disease and neurodegeneration: A brighter outlook? 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