Antibody Therapy Inspired by Patient Case Reduced Tau Tangles in a Preclinical Model of Alzheimer’s Disease

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<span>Medical Education</span> </a> </li> </ul> </li> <li> <ul class="cmp-global-header-main-nav-expanded-children-wrapper"> <li class="cmp-global-header-main-nav-expanded-childHeader"> For trainees </li> <li class="cmp-global-header-main-nav-expanded-subChildren"> <a href="/en/education-and-training/graduate-medical-education/for-trainees/prospective" target="_self"> <span>Prospective trainees</span> </a> </li> <li class="cmp-global-header-main-nav-expanded-subChildren"> <a href="/en/education-and-training/graduate-medical-education/for-trainees/incoming" target="_self"> <span>Incoming trainees</span> </a> </li> <li class="cmp-global-header-main-nav-expanded-subChildren"> <a href="/en/education-and-training/graduate-medical-education/for-trainees/current" target="_self"> <span>Current trainees</span> </a> </li> </ul> </li> </ul> </div> </li> <li> <a class="cmp-global-header-main-nav-item no-children mainNavigation-inactive internal" 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</a> <meta itemprop="position" content="2"/> </li> <li class="cmp-breadcrumb__item cmp-breadcrumb__item--active" aria-current="page" data-cmp-data-layer="{"breadcrumb-cb010836d2-item-774c3f843f":{"@type":"aem-mgb/components/breadcrumb/item","repo:modifyDate":"2023-10-04T19:26:09Z","dc:title":"Antibody Therapy Reduced Tau Tangles in a Preclinical Model of Alzheimer’s Disease","xdm:linkURL":"/en/about/newsroom/press-releases/antibody-therapy-reduced-tau-tangles-in-preclinical-model-of-alzheimers-disease"}}" itemprop="itemListElement" itemscope itemtype="http://schema.org/ListItem"> <span itemprop="name">Antibody Therapy Reduced Tau Tangles in a Preclinical Model of Alzheimer’s Disease</span> <meta itemprop="position" content="3"/> </li> </ol> </nav> </div> <div class="alert cmp-alert cmp-alert-page aem-GridColumn aem-GridColumn--default--12"> <div class="cmp-alert-main-container"> <div class="cmp-alert-container hidden" role="alert" tabindex="-1"> <div class="cmp-alert-content"> <div 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responsivegrid aem-GridColumn aem-GridColumn--default--12"> <div id="container-bb4423fc29" class="cmp-container"> <div class="aem-Grid aem-Grid--12 aem-Grid--default--12 "> </div> </div> </div> <div class="article-hero aem-GridColumn aem-GridColumn--default--12"><div> <div class="cmp-article-hero"> <h1 class="cmp-article-hero-title"> Antibody Therapy Inspired by Patient Case Reduced Tau Tangles in a Preclinical Model of Alzheimer’s Disease </h1> <div class="cmp-article-hero-info-wrapper"> <div class="cmp-article-hero-time-wrapper"> <div class="cmp-article-hero-date"><time datetime="2023-10-04">Oct 4, 2023</time> </div> </div> </div> <div class="cmp-article-hero-row"> <div class="cmp-article-hero-tags" role="region" aria-label="related topic tags"> <ul class="cmp-article-hero-tags-item-wrapper"> <li class="cmp-article-hero-tags-item"><a href="https://www.massgeneralbrigham.org/en/about/newsroom.topic=Patient%20Care">Patient Care</a></li> <li class="cmp-article-hero-tags-item"><a href="https://www.massgeneralbrigham.org/en/about/newsroom.topic=Brain%20&%20Nervous%20System%20Conditions">Brain & Nervous System Conditions</a></li> <li class="cmp-article-hero-tags-item"><a href="https://www.massgeneralbrigham.org/en/about/newsroom.topic=Ophthalmology">Ophthalmology</a></li> <li class="cmp-article-hero-tags-item"><a href="https://www.massgeneralbrigham.org/en/about/newsroom.topic=Research">Research</a></li> </ul> </div> <div class="cmp-article-hero-social-links" role="region" aria-label="share this article"> <ul class="cmp-article-hero-social-links-wrapper"> <li> <a href="#" class="cmp-article-hero-facebook"><span class="sr-only">share on facebook</span> <div class="cmp-article-hero-facebook-icon"></div> </a> </li> <li> <a href="#" class="cmp-article-hero-linkedin"><span class="sr-only">share on linkedIn</span> <div class="cmp-article-hero-linkedin-icon"></div> </a> </li> <li> <a href="#" class="cmp-article-hero-x-twitter"><span class="sr-only">share on X, formerly known as Twitter</span> <div class="cmp-article-hero-x-twitter-icon"></div> </a> </li> <li> <a href="#" class="cmp-article-hero-mail"><span class="sr-only">share by email</span> <div class="cmp-article-hero-mail-icon"></div> </a> </li> <li> <button class="cmp-article-hero-print"><span class="sr-only">print article</span> <div class="cmp-article-hero-print-icon"></div> </button> </li> </ul> </div> </div> </div> </div> </div> <div class="container responsivegrid cmp-container-1440-gutters aem-GridColumn aem-GridColumn--default--12"> <div id="container-7aee61f598" class="cmp-container"> <div class="aem-Grid aem-Grid--12 aem-Grid--default--12 "> <div class="text aem-GridColumn aem-GridColumn--default--12"> <div data-cmp-data-layer="{"text-e7c58c7e09":{"@type":"aem-mgb/components/text","repo:modifyDate":"2024-05-29T17:55:54Z","xdm:text":"<p>A team led by researchers from&nbsp;<a href=\"/content/mgb-global/global/en.html\">Mass General Brigham</a>&nbsp;reports promising results for a monoclonal antibody that takes aim at a new target for Alzheimer’s disease. Inspired by their&nbsp;<a href=\"https://www.massgeneral.org/news/press-release/alzheimer-denying-brain-offer-clues-treatment-prevention-dementia\" target=\"_blank\">previous identification of a genetic variant</a>&nbsp;in the APOE gene that provides extreme resistance against Alzheimer’s disease, the team, which includes investigators from&nbsp;<a href=\"https://www.masseyeandear.org/\" target=\"_blank\">Mass Eye and Ear</a>&nbsp;and&nbsp;<a href=\"https://www.massgeneral.org/\" target=\"_blank\">Massachusetts General Hospital</a>, developed a therapy that mimics the behavior of this genetic variant in a preclinical model, reducing abnormal tau proteins associated with Alzheimer’s disease and offering a path to treatment that does not target amyloid beta plaque buildups.</p>\r\n<p>This work&nbsp;<a href=\"https://www.masseyeandear.org/news/press-releases/2019/11/researchers-identify-genetic-mutation-tied-to-alzheimers-disease-protection\" target=\"_blank\">builds on previous research</a>&nbsp;led by this team that identified a genetic variant called APOE Christchurch that led to Alzheimer’s resistance and protection against cognitive decline for almost three decades in a woman in her 70s who was part of a family in Colombia at an unusually high genetic risk to develop early-onset disease. To turn those findings into a potential treatment, the researchers have now developed antibodies that could target interactions between ApoE and proteins called heparan sulfate proteoglycans, effectively mimicking the protective mechanism and effects of the Christchurch genetic variant. They used the crystal structure of the antibodies and computer modeling to predict how it would bind to the target of interest. They found that one antibody, called 7C11, could inhibit the pathological interaction, conferring resistance to Alzheimer’s. They validated the specificity of the antibody and determined the most effective doses to deliver. Their therapy, tested in mice, resulted in a reduction of abnormal tau proteins found in their brains and retinas.</p>\r\n<p>Study limitations include a short treatment duration applied to an early disease state. Future studies in additional animal models are necessary to confirm preclinical efficacy.</p>\r\n<p>“Our 7C11 antibody was able to target interactions responsible for a major genetic risk factor for sporadic Alzheimer’s,” said co-corresponding author <a href=\"https://researchers.masseyeandear.org/details/278/joseph-arboleda-velasquez\" target=\"_blank\">Joseph F. Arboleda-Velasquez, MD, PhD</a>, an associate scientist in the Department of Ophthalmology at Mass Eye and Ear. “Our findings point to an alternative and hopefully more effective approach to existing treatments and those in clinical trials that focus on reducing amyloid plaques, and ultimately may lead to disease-modifying therapies for various other neurodegenerative conditions.”</p>\r\n<p>“Remarkably, the subject with extreme protection against Alzheimer’s disease who carried the APOE Christchurch variant had a similar clinical presentation with much lower tau accumulation despite severe amyloid pathology,” said Claudia Marino, a research fellow who co-led the study with Arboleda-Velasquez. “In sum, the 7C11 antibody was able to reproduce in an&nbsp;<i>in vivo</i>&nbsp;model the protective effect of the APOE Christchurch variant.”</p>\r\n<p>Read more in&nbsp;<i><a href=\"https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.13436\" target=\"_blank\">Alzheimer's and Dementia: The Journal of the Alzheimer’s Association</a>.</i></p>\r\n"}}" id="text-e7c58c7e09" class="cmp-text"> <p>A team led by researchers from <a href="/en">Mass General Brigham</a> reports promising results for a monoclonal antibody that takes aim at a new target for Alzheimer’s disease. Inspired by their <a href="https://www.massgeneral.org/news/press-release/alzheimer-denying-brain-offer-clues-treatment-prevention-dementia" target="_blank">previous identification of a genetic variant</a> in the APOE gene that provides extreme resistance against Alzheimer’s disease, the team, which includes investigators from <a href="https://www.masseyeandear.org/" target="_blank">Mass Eye and Ear</a> and <a href="https://www.massgeneral.org/" target="_blank">Massachusetts General Hospital</a>, developed a therapy that mimics the behavior of this genetic variant in a preclinical model, reducing abnormal tau proteins associated with Alzheimer’s disease and offering a path to treatment that does not target amyloid beta plaque buildups.</p> <p>This work <a href="https://www.masseyeandear.org/news/press-releases/2019/11/researchers-identify-genetic-mutation-tied-to-alzheimers-disease-protection" target="_blank">builds on previous research</a> led by this team that identified a genetic variant called APOE Christchurch that led to Alzheimer’s resistance and protection against cognitive decline for almost three decades in a woman in her 70s who was part of a family in Colombia at an unusually high genetic risk to develop early-onset disease. To turn those findings into a potential treatment, the researchers have now developed antibodies that could target interactions between ApoE and proteins called heparan sulfate proteoglycans, effectively mimicking the protective mechanism and effects of the Christchurch genetic variant. They used the crystal structure of the antibodies and computer modeling to predict how it would bind to the target of interest. They found that one antibody, called 7C11, could inhibit the pathological interaction, conferring resistance to Alzheimer’s. They validated the specificity of the antibody and determined the most effective doses to deliver. Their therapy, tested in mice, resulted in a reduction of abnormal tau proteins found in their brains and retinas.</p> <p>Study limitations include a short treatment duration applied to an early disease state. Future studies in additional animal models are necessary to confirm preclinical efficacy.</p> <p>“Our 7C11 antibody was able to target interactions responsible for a major genetic risk factor for sporadic Alzheimer’s,” said co-corresponding author <a href="https://researchers.masseyeandear.org/details/278/joseph-arboleda-velasquez" target="_blank">Joseph F. Arboleda-Velasquez, MD, PhD</a>, an associate scientist in the Department of Ophthalmology at Mass Eye and Ear. “Our findings point to an alternative and hopefully more effective approach to existing treatments and those in clinical trials that focus on reducing amyloid plaques, and ultimately may lead to disease-modifying therapies for various other neurodegenerative conditions.”</p> <p>“Remarkably, the subject with extreme protection against Alzheimer’s disease who carried the APOE Christchurch variant had a similar clinical presentation with much lower tau accumulation despite severe amyloid pathology,” said Claudia Marino, a research fellow who co-led the study with Arboleda-Velasquez. “In sum, the 7C11 antibody was able to reproduce in an <i>in vivo</i> model the protective effect of the APOE Christchurch variant.”</p> <p>Read more in <i><a href="https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.13436" target="_blank">Alzheimer's and Dementia: The Journal of the Alzheimer’s Association</a>.</i></p> </div> </div> <div class="vertical-spacer aem-GridColumn aem-GridColumn--default--12"> <div class="cmp-vertical-spacer cmp-space-small" aria-hidden="true"></div> </div> <div class="experiencefragment aem-GridColumn aem-GridColumn--default--12"> <div id="experiencefragment-3720146e46" class="cmp-experiencefragment cmp-experiencefragment--media-contact"> <div id="container-acc133f168" class="cmp-container"> <div class="aem-Grid aem-Grid--12 aem-Grid--default--12 "> <div class="contact-block cmp-contact-block-contact cmp-contact-block-contact-standard aem-GridColumn aem-GridColumn--default--12"> <div class="cmp-contact-block-contact-container"> <div class="cmp-contact-block-details-container"> <div class="cmp-contact-block-details"> <h2 class="cmp-contact-block-title">Media contact</h2> <div class="cmp-contact-block-title-divider"></div> <div class="cmp-contact-block-details-info-container no-image"> <div class="cmp-contact-block-name"> <span class="cmp-contact-block-name-field">Ryan Jaslow</span> </div> <div class="cmp-contact-block-job-title">Program Director, External Communications (Research)</div> <div class="cmp-contact-block-email-phone"> <a class="cmp-contact-block-email-link" href="mailto: rjaslow@mgb.org">rjaslow@mgb.org</a> </div> </div> </div> <div class="cmp-contact-block-call-button"> <div class="global-button button cmp-injectedComponent"> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="vertical-spacer aem-GridColumn aem-GridColumn--default--12"> <div class="cmp-vertical-spacer cmp-space-small" aria-hidden="true"></div> </div> <div class="experiencefragment aem-GridColumn aem-GridColumn--default--12"> <div id="experiencefragment-df4ed60cfa" class="cmp-experiencefragment cmp-experiencefragment--about-mgb"> <div id="container-fe9f673ddd" class="cmp-container"> <div class="aem-Grid aem-Grid--12 aem-Grid--default--12 "> <div class="text aem-GridColumn aem-GridColumn--default--12"> <div data-cmp-data-layer="{"text-476c0441d5":{"@type":"aem-mgb/components/text","repo:modifyDate":"2024-01-11T23:56:50Z","xdm:text":"<h3>About Mass General Brigham</h3>\r\n<p>Mass General Brigham is an integrated academic health care system, uniting great minds to solve the hardest problems in medicine for our communities and the world. Mass General Brigham connects a full continuum of care across a system of academic medical centers, community and specialty hospitals, a health insurance plan, physician networks, community health centers, home care, and long-term care services. Mass General Brigham is a nonprofit organization committed to patient care, research, teaching, and service to the community. In addition, Mass General Brigham is one of the nation’s leading biomedical research organizations with several Harvard Medical School teaching hospitals. For more information, please visit <a href=\"https://www.massgeneralbrigham.org/en\" target=\"_self\">massgeneralbrigham.org</a>.</p>\r\n"}}" id="text-476c0441d5" class="cmp-text"> <h3>About Mass General Brigham</h3> <p>Mass General Brigham is an integrated academic health care system, uniting great minds to solve the hardest problems in medicine for our communities and the world. Mass General Brigham connects a full continuum of care across a system of academic medical centers, community and specialty hospitals, a health insurance plan, physician networks, community health centers, home care, and long-term care services. Mass General Brigham is a nonprofit organization committed to patient care, research, teaching, and service to the community. In addition, Mass General Brigham is one of the nation’s leading biomedical research organizations with several Harvard Medical School teaching hospitals. For more information, please visit <a href="https://www.massgeneralbrigham.org/en" target="_self">massgeneralbrigham.org</a>.</p> </div> </div> </div> </div> </div> </div> <div class="vertical-spacer aem-GridColumn aem-GridColumn--default--12"> <div class="cmp-vertical-spacer cmp-space-small" aria-hidden="true"></div> </div> <div class="experiencefragment aem-GridColumn aem-GridColumn--default--12"> <div id="experiencefragment-2f85f163c9" class="cmp-experiencefragment cmp-experiencefragment--research"> <div id="container-9df1c97296" class="cmp-container"> <div class="aem-Grid aem-Grid--12 aem-Grid--default--12 "> <div class="spotlight-news-grid aem-GridColumn aem-GridColumn--default--12"> <div class="cmp-spotlight-news-grid"> <div class="carousel-container carousel"> <h2 id="cmp-carousel-heading">Related research about Alzheimer’s disease</h2> <div id="cmp-carousel-status" class="carousel-status sr-only" role="status" aria-atomic="true">Displaying %1% to %2% of %3% items</div> <div class="carousel-button-container"> <button type="button" class="carousel-prev"><span class="sr-only">Previous carousel items</span></button> <button type="button" class="carousel-next"><span class="sr-only">Next carousel items</span></button> </div> <div class="carousel-items-container">    <ul class="carousel-items cmp-spotlight-news-grid__card-wrap"> <li class="carousel-item cmp-spotlight-news-grid__cards"> <div class="cmp-spotlight-news-grid__article-image"> <img class="article-image" src="/content/dam/mgb-global/en/about/newsroom/icons/neuro-brain-icon.png" alt="Maternal Inheritance of Alzheimer’s Disease Tied to Increased Risk of Developing Disease"/> </div> <div class="cmp-spotlight-news-grid__article-title"> <a class="article-title" href="/en/about/newsroom/press-releases/maternal-inheritance-of-alzheimers-increases-risk-of-developing-disease"> Maternal Inheritance of Alzheimer’s Disease Tied to Increased Risk of Developing Disease </a> </div> <div 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