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<\/a><\/p>\n\u201cInfectious agents have been implicated in the development and progression of Alzheimer\u2019s disease before, but the evidence of causation hasn\u2019t been convincing,\u201d said Stephen Dominy, M.D., Cortexyme co-founder, chief scientific officer, and lead author on the paper. \u201cNow, for the first time, we have solid evidence connecting the intracellular, Gram-negative pathogen, Pg, and Alzheimer\u2019s pathogenesis while also demonstrating the potential for a class of small molecule therapies to change the trajectory of disease.\u201d<\/p>\n
The Science Advances publication details how researchers identified Pg, the keystone pathogen in chronic periodontal disease, in the brains of patients with AD. In mouse models, oral Pg infection led to brain colonization and increased production of amyloid beta (A\u03b2), a component of the amyloid plaques commonly associated with Alzheimer\u2019s.<\/p>\n
In addition to Pg itself, the study team also detected the organism\u2019s toxic proteases, or gingipains, in the neurons of patients with AD. The team correlated the gingipain levels with pathology related to two markers: tau, a protein needed for normal neuronal function, and ubiquitin, a small protein tag that marks damaged proteins for degradation and is found in tau tangles and A\u03b2 plaques. The gingipains were found to be neurotoxic in vivo and in vitro, exerting detrimental effects on tau.<\/p>\n
Seeking to block Pg-driven neurotoxicity, Cortexyme set out to design a series of small molecule therapies targeting Pg gingipains. In preclinical experiments detailed in the paper, the researchers demonstrated that inhibition by COR388, the most promising compound in the series and the subject of Cortexyme\u2019s ongoing clinical development program, reduced the bacterial load of an established Pg brain infection, blocked A\u03b242 production, reduced neuroinflammation, and protected neurons in the hippocampus, the part of the brain that mediates memory and frequently atrophies early in the development of AD.<\/p>\n
\u201cDespite significant funding and the best efforts of academic, industry, and advocacy communities, clinical progress against Alzheimer\u2019s has been frustratingly slow,\u201d said Casey Lynch, Cortexyme\u2019s co-founder, chief executive officer, and an author on the Science Advances paper. \u201cThe Science Advances publication sheds light on an unexpected driver of Alzheimer\u2019s pathology \u2013 the bacterium commonly associated with chronic gum disease \u2013 and details the promising therapeutic approach Cortexyme is taking to address it with COR388.\u201d<\/p>\n
In October 2018, Cortexyme announced encouraging results from its Phase 1b clinical trial of COR388 at the 11th Clinical Trials in Alzheimer\u2019s Disease Conference. Investigators reported the compound was safe and well tolerated in healthy older volunteers and Alzheimer\u2019s patients when given at a range of doses for up to 28 days. COR388 was detectable in the cerebral spinal fluid (CSF) along with fragmented DNA from the bacterium that COR388 targets. Additionally, while the study was not powered for significance, COR388 showed positive trends across several cognitive tests in patients suffering from AD. Cortexyme plans to initiate a large Phase 2\/3 clinical trial of COR388 in mild to moderate AD in 2019.<\/p>\n
Read the Science Advances paper in full here:<\/p>\n
http:\/\/advances.sciencemag.org\/content\/5\/1\/eaau3333<\/p>\n
About Cortexyme<\/p>\n
Cortexyme is a privately held, clinical-stage pharmaceutical company developing therapeutics to alter the course of Alzheimer\u2019s and other degenerative disorders. Cortexyme is targeting a specific, infectious pathogen tied to neurodegeneration and chronic inflammation in humans and animal models. The company\u2019s lead compound, COR388, is entering Phase 2\/3 development; additional proprietary small molecules are moving forward in preclinical development. Cortexyme\u2019s investors include Sequoia Capital, Vulcan Capital, Verily Life Sciences, EPIQ Capital Group, RSL Investments, Lamond Family, Pfizer, Takeda Ventures, Breakout Ventures, Dolby Family Ventures, and Breakout Labs among others. For more information on Cortexyme, visit www.cortexyme.com.<\/p>\n","protected":false},"excerpt":{"rendered":"
South San Francisco CA…Cortexyme, Inc., the privately held, clinical-stage pharmaceutical company developing therapeutics to alter the course of Alzheimer\u2019s disease (AD) and other degenerative disorders, has announced publication of a foundational paper supporting its approach in Science Advances, a top-ranked multidisciplinary journal published by the American Association for the Advancement of Science (AAAS). In the […]<\/p>\n","protected":false},"author":1,"featured_media":73517,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_cbd_carousel_blocks":"[]","jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-73515","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","last_archivepost"],"jetpack_featured_media_url":"https:\/\/new.thepinetree.net\/wp-content\/uploads\/2019\/01\/F1.large_.jpg","jetpack_sharing_enabled":true,"jetpack-related-posts":[],"_links":{"self":[{"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/posts\/73515","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=73515"}],"version-history":[{"count":0,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/posts\/73515\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=\/wp\/v2\/media\/73517"}],"wp:attachment":[{"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=73515"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=73515"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/new.thepinetree.net\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=73515"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}