Identification of Safe and Effective Intravenous Dose of AAVrh.10hFXN to Treat the Cardiac Manifestations of Friedreich's Ataxia

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new collection</label> </li> <li> <input type="radio" id="collections-action-panel-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="save_share" data-ga-action="collections" data-ga-label="collections_radio_existing"> <label for="collections-action-panel-existing">Add to an existing collection</label> </li> </ul> </div> <div class="controls-wrapper"> <div class="action-panel-control-wrap new-collections-controls"> <label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label> <input type="text" name="add-to-new-collection" id="collections-action-panel-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="save_share" data-ga-action="create_collection" data-ga-label="non_favorties_collection"> <div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div> </div> <div class="action-panel-control-wrap existing-collections-controls"> <label for="collections-action-panel-add-to-existing" class="action-panel-label"> Choose a collection: </label> <select id="collections-action-panel-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="save_share" data-ga-action="select_collection" data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"> </select> <div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br> <a href="#">Please try again</a> </div> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="save_share" data-ga-action="collections" data-ga-label="add"> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="collections" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="bibliography-action-panel" class="bibliography-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-bibliography-open-panel-enabled="false" data-bibliography-open-panel-url-hash="#open-bibliography-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to My Bibliography </h3> <form id="bibliography-action-panel-form" class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-add-to-bibliography-max-amount="100" data-add-to-bibliography-batch-size="10" data-bibliography-delegates-url="/list-bibliography-delegates/" data-add-to-bibliography-url="/add-to-bibliography/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/"> <input type="hidden" name="csrfmiddlewaretoken" value="nAcGqEq7hfSVftWaQV7rdVy0kJZ8lWuDgCtS2DOCYTKaddCmtH6mRWiZBqMz6YOs"> <div class="action-panel-control-wrap bibliographies-controls"> <div class="choice-group"> <ul class="bibliographies-action-add radio-group-items"> <li> <input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/> <label for="my-bibliography">My Bibliography</label> </li> </ul> </div> </div> <div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your delegates due to an error<br> <a href="#">Please try again</a> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to bibliography' panel" ref="linksrc=close_bibliography_panel" aria-controls="bibliography-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="mybib" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true" data-saved-search-open-panel-enabled="false" data-saved-search-open-panel-url-hash="#open-saved-search-panel"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your saved search </h2> <form id="saved-search-action-panel-form" class="saved-search-action-panel-form action-panel-content action-form" data-create-saved-search-url="/create-saved-search/" data-try-search-terms-url="/try-search-term/" data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/"> <input type="hidden" name="csrfmiddlewaretoken" value="nAcGqEq7hfSVftWaQV7rdVy0kJZ8lWuDgCtS2DOCYTKaddCmtH6mRWiZBqMz6YOs"> <div class="action-panel-control-wrap"> <label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk"> Name of saved search: </label> <input maxlength="200" type="text" name="saved-search-name" id="saved-search-name" class="saved-search-name" value="" required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="action-panel-control-wrap"> <label for="saved-search-term" class="action-panel-label required-field-asterisk"> Search terms: </label> <textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea> </div> <div class="test-search-term-wrap"> <a href="#" class="try-search-term">Test search terms</a> </div> <div class="choice-group action-panel-extra-margin-top"> <span class="action-panel-label" id="fieldset-label"> Would you like email updates of new search results? </span> <fieldset id="saved-search-alert" aria-describedby="fieldset-label"> <legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend> <ul class="radio-group-items"> <li> <input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked> <label for="saved-search-alert-yes" class="action-panel-label">Yes</label> </li> <li> <input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no"> <label for="saved-search-alert-no" class="action-panel-label">No</label> </li> </ul> </fieldset> </div> <div class="alert-schedule-wrap"> <div class="action-panel-control-wrap"> <label class="action-panel-label"> Email: </label> <span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span> </div> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="saved-search-frequency" class="action-panel-label"> Frequency: </label> <select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency"> <option value="monthly">Monthly</option> <option value="weekly">Weekly</option> <option value="daily">Daily</option> </select> </div> <div class="action-panel-control-wrap saved-search-monthly-additional"> <label for="saved-search-monthly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-monthly-on-day" class="no-border-panel-selector"> <option value="Sunday">The first Sunday</option> <option value="Monday">The first Monday</option> <option value="Tuesday">The first Tuesday</option> <option value="Wednesday">The first Wednesday</option> <option value="Thursday">The first Thursday</option> <option value="Friday">The first Friday</option> <option value="Saturday">The first Saturday</option> <option value="day">The first day</option> <option value="weekday">The first weekday</option> </select> </div> <div class="action-panel-control-wrap saved-search-weekly-additional"> <label for="saved-search-weekly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day"> <option value="Sunday">Sunday</option> <option value="Monday">Monday</option> <option value="Tuesday">Tuesday</option> <option value="Wednesday">Wednesday</option> <option value="Thursday">Thursday</option> <option value="Friday">Friday</option> <option value="Saturday">Saturday</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-report" class="action-panel-label"> Report format: </label> <select id="saved-search-report" class="no-border-panel-selector saved-search-report"> <option value="DocSum">Summary</option> <option value="DocSumText">Summary (text)</option> <option value="Abstract">Abstract</option> <option value="AbstractText">Abstract (text)</option> <option value="MEDLINE">PubMed</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-amount" class="action-panel-label"> Send at most: </label> <select id="saved-search-amount" class="no-border-panel-selector saved-search-amount"> <option value="1">1 item</option> <option value="5" selected>5 items</option> <option value="10">10 items</option> <option value="20">20 items</option> <option value="50">50 items</option> <option value="100">100 items</option> <option value="200">200 items</option> </select> </div> <div> <input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result"> <label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox"> Send even when there aren't any new results </label> </div> <div class="action-panel-control-wrap option-text-in-email-wrap"> <label for="saved-search-email-text" class="action-panel-label"> Optional text in email: </label> <textarea name="saved-search-email-text" id="saved-search-email-text" class="saved-search-email-text"></textarea> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Save </button> <button class="action-panel-cancel" aria-label="Close 'Your saved search' panel" ref="linksrc=close_saved_search_panel" aria-controls="saved-search-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Create a file for external citation management software </h2> <form id="citation-manager-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="nAcGqEq7hfSVftWaQV7rdVy0kJZ8lWuDgCtS2DOCYTKaddCmtH6mRWiZBqMz6YOs"> <input name="results-format" type="hidden" value="pubmed"/> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Send citations to citation manager' panel" ref="linksrc=close_citation_manager_panel" aria-controls="citation-manager-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your RSS Feed </h2> <form id="rss-action-panel-form" class="rss-action-panel-form action-panel-content action-form" data-create-rss-feed-url="/create-rss-feed-url/" data-search-form-term-value=""> <input type="hidden" name="csrfmiddlewaretoken" value="nAcGqEq7hfSVftWaQV7rdVy0kJZ8lWuDgCtS2DOCYTKaddCmtH6mRWiZBqMz6YOs"> <div class="action-panel-control-wrap"> <label for="rss-name" class="action-panel-label required-field-asterisk"> Name of RSS Feed: </label> <input maxlength="200" placeholder="Name" type="text" name="rss-name" id="rss-name" class="rss-name" value='' required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="rss-limit-wrap"> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="rss-limit" class="action-panel-label"> Number of items displayed: </label> <select id="rss-limit" class="no-border-panel-selector rss-limit"> <option value="5">5</option> <option value="10">10</option> <option value="15" selected="selected">15</option> <option value="20">20</option> <option value="50">50</option> <option value="100">100</option> </select> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Creating..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Create RSS </button> <button class="action-panel-cancel" aria-label="Close 'Your RSS' panel" ref="linksrc=close_rss_panel" aria-controls="rss-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> <div class="action-panel-control-wrap rss-link-copy-wrap"> <label for="rss-link" class="usa-sr-only">RSS Link</label> <input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link"> <button type="button" disabled class="rss-link-copy-button disabled" data-ga-category="save_share" data-ga-action="rss" data-ga-label="copy"> Copy </button> </div> </form> </div> </div> </div> </div> <div class="article-page" id="article-page" data-article-pmid="37166361"> <aside class="page-sidebar"> <div class="inner-wrap"> <div class="full-text-links"> <div class="full-view"> <h3 class="title"> Full text links </h3> <div class="full-text-links-list"> <a class="link-item dialog-focus" 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required-field-asterisk"> Name your collection: </label><input type="text" name="add-to-new-collection" id="collections-action-dialog-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="collections_button" data-ga-action="create_collection" data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label"> Choose a collection: </label><select id="collections-action-dialog-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="collections_button" data-ga-action="select_collection" data-ga-label="($('.collections-action-add-to-existing').val() === 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'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="collections_button" data-ga-action="click" data-ga-label="add"> Add </button><button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="collections_button" data-ga-action="click" data-ga-label="cancel"> Cancel </button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" 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id="full-view-journal-trigger" class="journal-actions-trigger trigger" ref="linksrc=journal_actions_btn" title="Human gene therapy" tabindex="0" aria-controls="full-view-journal" aria-expanded="false" aria-label="Toggle dropdown menu for journal Human gene therapy" data-pinger-ignore> Hum Gene Ther </button><div id="full-view-journal" class="journal-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for journal Human gene therapy"><div class="title">Actions</div><div class="content"><ul class="journal-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Hum+Gene+Ther%22%5Bjour%5D&sort=date&sort_order=desc" data-href="/?term=%22Hum+Gene+Ther%22%5Bjour%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_journal_name_link&journal_abbrev=Hum Gene Ther" data-ga-category="search" data-ga-action="journal_link" data-ga-label="Hum Gene Ther"> Search in PubMed </a></li><li><a class="search-in-nlm-catalog-link 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class="authors"> <div class="authors-list"> <span class="authors-list-item "><a class="full-name" href="/?term=Munoz-Zuluaga+C&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Carlos Munoz-Zuluaga">Carlos Munoz-Zuluaga</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Gertz+M&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Monica Gertz">Monica Gertz</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Yost-Bido+M&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Melissa Yost-Bido">Melissa Yost-Bido</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Greco+A&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Alessandria Greco">Alessandria Greco</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Gorman+N&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Nicholas Gorman">Nicholas Gorman</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Chen+A&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Alvin Chen">Alvin Chen</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Kooner+V&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Vikrum Kooner">Vikrum Kooner</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Rosenberg+JB&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Jonathan B Rosenberg">Jonathan B Rosenberg</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=De+BP&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Bishnu P De">Bishnu P De</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Kaminsky+SM&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Stephen M Kaminsky">Stephen M Kaminsky</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Borczuk+A&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Alain Borczuk">Alain Borczuk</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Pathology, Weill Cornell Medicine, New York, New York, USA." href="#full-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Ricart+Arbona+RJ&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Rodolfo J Ricart Arbona">Rodolfo J Ricart Arbona</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Center for Comparative Medicine and Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, New York, USA." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Martin+HR&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Heather R Martin">Heather R Martin</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Center for Comparative Medicine and Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, New York, USA." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Monette+S&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Sebastien Monette">Sebastien Monette</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Center for Comparative Medicine and Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, New York, USA." href="#full-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Khanna+R&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Richie Khanna">Richie Khanna</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="LEXEO Therapeutics, New York, New York, USA." href="#full-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Barth+JA&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Jay A Barth">Jay A Barth</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="LEXEO Therapeutics, New York, New York, USA." href="#full-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Crystal+RG&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Ronald G Crystal">Ronald G Crystal</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Sondhi+D&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Dolan Sondhi">Dolan Sondhi</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#full-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup></span> </div> </div> </div> <div class="short-article-details"> Affiliations <button class="more-details" id="toggle-authors" data-alt-text="Collapse" aria-controls="expanded-authors" aria-expanded="false" data-pinger-ignore data-fetch-url="/37166361/long-authors/" data-id-prefix=""> <span class="title"> Expand </span> </button> </div> <div class="extended-article-details" id="expanded-authors" aria-hidden="true"> <div class="expanded-authors" id="full-view-expanded-authors"> <div 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Friedreich's Ataxia </h1> <div class="short-citation"> <span class="authors-list"> <span class="authors-list-item "><span class="full-name">Carlos Munoz-Zuluaga</span><span class="citation-separator"> et al.</span></span> </span> <span class="citation-journal"> Hum Gene Ther<span class="citation-separator">.</span> </span> <span class="date"> <span class="citation-year">2023 Jul</span><span class="citation-separator">.</span> </span> </div> <div class="more-article-details-section with-display-settings"> <button class="more-article-details" id="toggle-article-details" data-alt-text="Hide details" ref="linksrc=toggle_article_details" aria-controls="full-article-details" aria-expanded="false" data-fetch-url="/37166361/long-authors/" data-id-prefix=""> <span class="title">Show details</span> </button> <div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"> <button class="trigger usa-button" 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Munoz-Zuluaga</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Gertz+M&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Monica Gertz">Monica Gertz</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Yost-Bido+M&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Melissa Yost-Bido">Melissa Yost-Bido</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Greco+A&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Alessandria Greco">Alessandria Greco</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Gorman+N&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Nicholas Gorman">Nicholas Gorman</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Chen+A&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Alvin Chen">Alvin Chen</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Kooner+V&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Vikrum Kooner">Vikrum Kooner</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Rosenberg+JB&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Jonathan B Rosenberg">Jonathan B Rosenberg</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=De+BP&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Bishnu P De">Bishnu P De</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Kaminsky+SM&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Stephen M Kaminsky">Stephen M Kaminsky</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Borczuk+A&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Alain Borczuk">Alain Borczuk</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Pathology, Weill Cornell Medicine, New York, New York, USA." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Ricart+Arbona+RJ&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Rodolfo J Ricart Arbona">Rodolfo J Ricart Arbona</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Center for Comparative Medicine and Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, New York, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Martin+HR&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Heather R Martin">Heather R Martin</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Center for Comparative Medicine and Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, New York, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Monette+S&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Sebastien Monette">Sebastien Monette</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Center for Comparative Medicine and Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, New York, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff"> 3 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Khanna+R&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Richie Khanna">Richie Khanna</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="LEXEO Therapeutics, New York, New York, USA." href="#short-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Barth+JA&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Jay A Barth">Jay A Barth</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="LEXEO Therapeutics, New York, New York, USA." href="#short-view-affiliation-4" ref="linksrc=author_aff"> 4 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Crystal+RG&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Ronald G Crystal">Ronald G Crystal</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name" href="/?term=Sondhi+D&cauthor_id=37166361" ref="linksrc=author_name_link" data-ga-category="search" data-ga-action="author_link" data-ga-label="Dolan Sondhi">Dolan Sondhi</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Genetic Medicine, New York, New York, USA." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a></sup></span> </div> </div> <div class="affiliations"> <h3 class="title"> Affiliations </h3> <ul class="item-list"> <li data-affiliation-id="short-view-affiliation-1" id="short-view-affiliation-1" ><sup class="key">1</sup> Department of Genetic Medicine, New York, New York, USA.</li> <li data-affiliation-id="short-view-affiliation-2" id="short-view-affiliation-2" ><sup class="key">2</sup> Department of Pathology, Weill Cornell Medicine, New York, New York, USA.</li> <li data-affiliation-id="short-view-affiliation-3" id="short-view-affiliation-3" ><sup class="key">3</sup> Center for Comparative Medicine and Pathology, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, New York, USA.</li> <li data-affiliation-id="short-view-affiliation-4" id="short-view-affiliation-4" ><sup class="key">4</sup> LEXEO Therapeutics, New York, New York, USA.</li> </ul> </div> </div> <ul class="identifiers" id="short-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">37166361</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=PMC10354731&id_type=PMC" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC10354731/" data-ga-category="full_text" data-ga-action="PMCID" > PMC10354731 </a> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.1089/hum.2023.020&id_type=DOI" href="https://doi.org/10.1089/hum.2023.020" data-ga-category="full_text" data-ga-action="DOI" > 10.1089/hum.2023.020 </a> </span> </li> </ul> <div class="in-clipboard-label " hidden> Item in Clipboard </div> </div> </div> </header> <div class="actions-buttons inline"><div class="inner-wrap"><button class="full-text-links-button full-text-links-dialog-trigger" title="Open dialog with full text links" ref="linksrc=full_text_links"> Full text links </button><button class="citation-button citation-dialog-trigger" aria-label="Open dialog with citation text in different styles" data-ga-category="save_share" data-ga-action="cite" data-ga-label="open" data-all-citations-url="/37166361/citations/" data-citation-style="nlm" data-pubmed-format-link="/37166361/export/"><span class="button-label">Cite</span></button><button class="more-actions-button more-actions-dialog-trigger" title="Open dialog with more actions to take" ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format" data-default-format-value="abstract" data-current-format-value="abstract" role="region"><button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title"> Display options </div><div class="content"><div class="format-container"><span class="option-label"> Format </span><select name="format" data-initial-value="abstract" aria-label="Display format" id="inline-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="abstract" id="abstract"> <h2 class="title"> Abstract </h2> <div class="abstract-content selected" id="eng-abstract"> <p> Friedreich's ataxia (FA) is a life-threatening autosomal recessive disorder characterized by neurological and cardiac dysfunction. Arrhythmias and heart failure are the main cause of premature death. From prior studies in murine models of FA, adeno-associated virus encoding the normal human frataxin gene (AAVrh.10hFXN) effectively treated the cardiac manifestations of the disease. However, the therapeutic dose window is limited by high level of human frataxin (hFXN) gene expression associated with toxicity. As a therapeutic goal, since FA heterozygotes have no clinical manifestations of FA, we estimated the level of frataxin (FXN) necessary to convert the heart of a homozygote to that of a heterozygote. In noncardiac cells, FA heterozygotes have 30-80% of normal FXN levels (17.7-47.2 ng/mg, average 32.5 ng/mg) and FA homozygotes 2-30% normal levels (1.2-17.7 ng/mg, average 9.4 ng/mg). Therefore, an AAV vector would need to augment endogenous in an FA homozygote by >8.3 ng/mg. To determine the required dose of AAVrh.10hFXN, we administered 1.8 × 10<sup>11</sup>, 5.7 × 10<sup>11</sup>, or 1.8 × 10<sup>12</sup> gc/kg of AAVrh.10hFXN intravenously (IV) to muscle creatine kinase (mck)-Cre conditional knockout <i>Fxn</i> mice, a cardiac and skeletal FXN knockout model. The minimally effective dose was 5.7 × 10<sup>11</sup> gc/kg, resulting in cardiac hFXN levels of 6.1 ± 4.2 ng/mg and a mild (<i>p</i> < 0.01 compared with phosphate-buffered saline controls) improvement in mortality. A dose of 1.8 × 10<sup>12</sup> gc/kg resulted in cardiac hFXN levels of 33.7 ± 6.4 ng/mg, a significant improvement in ejection fraction and fractional shortening (<i>p</i> < 0.05, both comparisons) and a 21.5% improvement in mortality (<i>p</i> < 0.001). To determine if the significantly effective dose of 1.8 × 10<sup>12</sup> gc/kg could achieve human FA heterozygote levels in a large animal, this dose was administered IV to nonhuman primates. After 12 weeks, the vector-expressed FXN in the heart was 17.8 ± 4.9 ng/mg, comparable to the target human levels. These data identify both minimally and significantly effective therapeutic doses that are clinically relevant for the treatment of the cardiac manifestations of FA. </p> </div> <p> <strong class="sub-title"> Keywords: </strong> Friedreich's ataxia; adeno-associated virus; cardiac gene therapy; dose-finding study. </p> </div> <p class="disclaimer" id="disclaimer"> <a href="/disclaimer/" target="_blank" ga_category="literature_resources" ga_action="disclaimer_link" ga_label="under_abstract">PubMed Disclaimer</a> </p> <div class="conflict-of-interest" id="conflict-of-interest"> <h2 class="title"> Conflict of interest statement </h2> <div class="statement"> <p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">D.S., S.M.K., and R.G.C. hold equity in and are consultants to LEXEO. R.K. and J.A.B. are employees of Lexeo Therapeutics.</p> </div> </div> <div class="figures" id="figures"> <h2 class="title"> Figures </h2> <div class="figures-list" id="slides-container" itemscope itemtype="http://schema.org/ImageGallery"> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="0" data-label-slug="figure-1"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b79/10354731/44b5159f10b7/hum.2023.020_figure1.jpg" itemprop="contentUrl" aria-describedby="figure-caption-0" role="button" data-image-width="716" data-image-height="1239" data-image-alt="Figure 1." data-pmc-id="PMC10354731" data-figure-id="f1"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-0" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b79/10354731/3be374d44f86/hum.2023.020_figure1.gif" alt="Figure 1." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="716"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="1239"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 1. </p> </strong> <div class="figure-caption-contents"><p> FXN protein levels in the… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 1. </p> </strong> <div class="figure-caption-contents"><p> FXN protein levels in the non-FA and FA human heart. <b> (A) </b> Human cardiac… </p></div> </div> <figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 1. </strong> <div class="figure-caption-contents">FXN protein levels in the non-FA and FA human heart. <b>(A)</b> Human cardiac FXN levels in individuals who do not have FA. Heart samples from five subjects at autopsy were obtained from the Department of Pathology at Weill Cornell Medicine. For each heart, the septum, left ventricle (including lateral, posterior, and anterior walls), and right ventricle were assessed. Samples were analyzed in triplicate (mean ± SEM). Subject 1 (80-year-old male, White), <i>yellow circle</i>; Subject 2 (75-year-old male, Hispanic), <i>red pentagram</i>; Subject 3 (65-year-old female, African American), <i>blue triangle</i>; Subject 4 (73-year-old female, White), <i>green square</i>; and Subject 5 (72-year-old male, White), <i>purple diamond</i>. Although there was subject to subject variability, on average, FXN levels in the different heart regions were similar (<i>p</i> ≥ 0.06). The mean of all heart samples was 59 ± 5 ng FXN/mg protein (<i>dashed line</i>). <b>(B)</b> FXN levels in human FA homozygote and heterozygote heart estimated using the mean normal levels <b>(A)</b> extrapolated to the heart using the FXN levels in noncardiac tissues in FA homozygous and heterozygotes (see FXN levels in a non-FA disease heart in the Results section and Lazaropoulos et al.). FA, Friedreich's ataxia; FXN, frataxin; SEM, standard error of the mean.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="1" data-label-slug="figure-2"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b79/10354731/ecbc4a56255b/hum.2023.020_figure2.jpg" itemprop="contentUrl" aria-describedby="figure-caption-1" role="button" data-image-width="625" data-image-height="1030" data-image-alt="Figure 2." data-pmc-id="PMC10354731" data-figure-id="f2"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-1" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b79/10354731/9603f26f3eae/hum.2023.020_figure2.gif" alt="Figure 2." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="625"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="1030"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 2. </p> </strong> <div class="figure-caption-contents"><p> Body weights of treated MCK… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 2. </p> </strong> <div class="figure-caption-contents"><p> Body weights of treated MCK mice post-administration. The average life span of untreated… </p></div> </div> <figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 2. </strong> <div class="figure-caption-contents">Body weights of treated MCK mice post-administration. The average life span of untreated MCK mice is 11 weeks. As a measure of overall health, MCK mice were weighed at regular intervals after vector or PBS treatment until they became moribund (Supplementary Table S1). The mean weights (g) ± SEM are shown for time of assessment after vector administration, with males (<i>squares</i>) and females (<i>triangles</i>) separately. All mice were treated at 7 weeks of age ±1–2 days. Group 1 mice (1.8 × 10<sup>11</sup> gc/kg dose, <i>blue symbols</i>); Group 2 mice (5.7 × 10<sup>11</sup> gc/kg dose, <i>green symbols</i>); Group 3 mice (1.8 × 10<sup>12</sup> gc/kg, <i>red symbols</i>); Group 4 mice (PBS controls, <i>gray symbols</i>). <b>(A)</b> Males; <b>(B)</b> Females. MCK, muscle creatine kinase (mck)-Cre conditional knockout <i>Fxn</i> mouse model; PBS, phosphate-buffered saline.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="2" data-label-slug="figure-3"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b79/10354731/ca2559e2e90e/hum.2023.020_figure3.jpg" itemprop="contentUrl" aria-describedby="figure-caption-2" role="button" data-image-width="750" data-image-height="841" data-image-alt="Figure 3." data-pmc-id="PMC10354731" data-figure-id="f3"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-2" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b79/10354731/903d8d5472a9/hum.2023.020_figure3.gif" alt="Figure 3." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="750"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="841"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 3. </p> </strong> <div class="figure-caption-contents"><p> Echocardiographic assessment of cardiac function… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 3. </p> </strong> <div class="figure-caption-contents"><p> Echocardiographic assessment of cardiac function of FXN-MCK mice and controls following treatment with… </p></div> </div> <figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 3. </strong> <div class="figure-caption-contents">Echocardiographic assessment of cardiac function of FXN-MCK mice and controls following treatment with AAVrh.10hFXN. Mice from each treatment group were monitored over time with echocardiography (see the Methods section). M-mode measurements were recorded for the short axis of the left ventricle at the midventricular level. <b>(A–I)</b> Representative echocardiogram tracings of the left ventricle for the same male mouse at 3 time points (7, 9, and 11 weeks of age, with the 7-week time point just before treatment and the 9- and 11-week assessments post-treatment) from each cohort. Description of the echocardiogram tracings in each panel, <i>top</i> to <i>bottom</i>: <i>Top yellow line</i> in each image traces the epicardial border along the anterior wall of the left ventricle, the <i>second yellow line</i> is a trace of the anterior endocardial wall border from full systole to full diastole. The <i>third yellow line</i> from the top traces the endocardial border of the posterior wall; the <i>bottom yellow line</i> traces the epicardial border of the posterior wall. The <i>top two</i> and <i>bottom two lines</i> together measure the wall thickness of the anterior and posterior wall of the left ventricle, respectively. The <i>vertical red</i> and <i>green lines</i> (<i>left</i> to <i>right</i> in each panel) measure the chamber of the left ventricle at full diastole and full systole, respectively. <b>(A–C)</b> WT untreated mouse control at 41, 64, and 76 days. <b>(D–F)</b> MCK mouse, PBS treated control at 42 and 63 days. <b>(G–I)</b> MCK mouse, 1.8 × 10<sup>12</sup> gc/kg dose at 42, 63, and 76 days. No mice in the PBS-treated MCK mouse cohort survived to the 11-week assessment time point. <b>(J, K)</b> Quantitative assessment of ejection fraction and fractional shortening calculated from the M-mode measurements of the short axis. <b>(J)</b> Change in ejection fraction (%) over time of WT C57Bl/6, PBS-treated, and AAVrh.10hFXN (1.8 × 10<sup>12</sup> gc/kg)-treated MCK mice. <b>(K)</b> Change in fractional shortening (%) in the same mice. Shown is the mean and standard error of percent change. All measurements were performed at 6 weeks (1 week before treatment), 9, 11, and 15 weeks of age for all surviving mice. Data from males and females were combined for each dosage cohort, shown as mean ± SEM. C57Bl/6 WT mice, <i>yellow circles</i>; MCK mice treated with AAVrh.10hFXN, 1.8 × 10<sup>12</sup> gc/kg dose, <i>red circles</i>; and MCK mice with PBS (controls), <i>black circles</i>. AAVrh.10hFXN, adeno-associated virus encoding the normal human frataxin gene; M-mode, motion mode; WT, wild type.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="3" data-label-slug="figure-4"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b79/10354731/0498560670f8/hum.2023.020_figure4.jpg" itemprop="contentUrl" aria-describedby="figure-caption-3" role="button" data-image-width="625" data-image-height="440" data-image-alt="Figure 4." data-pmc-id="PMC10354731" data-figure-id="f4"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-3" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b79/10354731/ba442ea89ba9/hum.2023.020_figure4.gif" alt="Figure 4." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="625"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="440"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 4. </p> </strong> <div class="figure-caption-contents"><p> Dose–response survival of MCK mice… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 4. </p> </strong> <div class="figure-caption-contents"><p> Dose–response survival of MCK mice administered AAVrh.10hFXN. MCK mice were intravenously administered AAVrh.10hFXN… </p></div> </div> <figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 4. </strong> <div class="figure-caption-contents">Dose–response survival of MCK mice administered AAVrh.10hFXN. MCK mice were intravenously administered AAVrh.10hFXN at 3 different doses (1.8 × 10<sup>11</sup>, 5.7 × 10<sup>11</sup>, and 1.8 × 10<sup>12</sup> gc/kg) or PBS at 7 weeks of age (±2 days, at 48–50 days). Mice were euthanized when moribund. Survival plots (Kaplan–Meier) were plotted for each dose cohort, with survival curves slightly offset on <i>y</i>-axis to show all the data. MCK mice with AAVrh.10hFXN, 1.8 × 10<sup>11</sup> gc/kg dose, <i>blue line</i>; 5.7 × 10<sup>11</sup> gc/kg dose, <i>green line</i>; 1.8 × 10<sup>12</sup> gc/kg dose, <i>red line</i>; MCK mice with PBS (controls), <i>black solid line</i>. <i>Black dashed line</i>, 50% survival. Comparison of treated versus PBS survival curves was analyzed with log-rank (Mantel–Cox) test, with log-rank test for trend. *<i>p</i> < 0.01 for 5.7 × 10<sup>11</sup> gc/kg dose group and <i>p</i> < 0.0001 for the 1.8 × 10<sup>12</sup> gc/kg dose.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="4" data-label-slug="figure-5"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b79/10354731/b5bcb46a1c7f/hum.2023.020_figure5.jpg" itemprop="contentUrl" aria-describedby="figure-caption-4" role="button" data-image-width="797" data-image-height="516" data-image-alt="Figure 5." data-pmc-id="PMC10354731" data-figure-id="f5"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-4" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b79/10354731/c9268fdae9df/hum.2023.020_figure5.gif" alt="Figure 5." /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="797"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="516"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 5. </p> </strong> <div class="figure-caption-contents"><p> Dose-dependent cardiac FXN levels following… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 5. </p> </strong> <div class="figure-caption-contents"><p> Dose-dependent cardiac FXN levels following AAVrh.10hFXN treatment of MCK mice <b> (A, B) </b> and… </p></div> </div> <figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 5. </strong> <div class="figure-caption-contents">Dose-dependent cardiac FXN levels following AAVrh.10hFXN treatment of MCK mice <b>(A, B)</b> and NHPs <b>(C, D)</b> and correlation of these to estimated cardiac FXN levels in FA homozygotes and heterozygotes. <b>(A)</b> Dose-dependent human cardiac FXN levels in MCK mice intravenously administered AAVrh.10hFXN at 1.8 × 10<sup>11</sup>, 5.7 × 10<sup>11</sup>, and 1.8 × 10<sup>12</sup> gc/kg (3 male and 3 female/dose, except the highest dose group 4 male/4 female). PBS-administered mice (3 male/3 female) served as negative control. At sacrifice, hFXN levels in the heart were assessed. The AAV-expressed human FXN levels in the treated mouse hearts (left ventricular wall) were measured in triplicate by ELISA and expressed as ng/mg total protein (mean ± SEM) of male and female combined for each dose group. Human FXN levels are shown versus AAVrh.10hFXN dose (log scale). <b>(B)</b> Estimated FXN cardiac levels in FA homozygotes based on the AAVrh.10FXN dose-dependent cardiac levels achieved in the MCK mice. The human FXN levels obtained in the MCK mouse in <b>(A)</b> were combined with the estimated endogenous human heart FXN levels in FA homozygotes (Fig. 1). The vector-derived hFXN levels observed in MCK mice (<i>red bars</i>) were added to the estimated endogenous cardiac FXN levels of 9.4 ng/mg estimated in FA homozygotes (<i>blue bars</i>), which allows for the estimation of the FXN levels obtained from a given dose of AAVrh.10hFXN. The <i>gray shading</i> represents the FXN level range estimated in FA carriers (heterozygotes). <b>(C)</b> NHP cardiac FXN levels following dose-dependent administration of AAVrh.10hFXN. Shown is the average of FXN protein levels in the heart (5 samples/NHP) assessed by ELISA of <i>n</i> = 4 (2 male, 2 female) NHPs administered 5.7 × 10<sup>11</sup> gc/kg and <i>n</i> = 4 (2 male, 2 female) administered 1.8 × 10<sup>12</sup> gc/kg. Data shown as mean ± SEM of 5 heart regions combined, for all animals for each dose group, with the mean values above each bar. The human FXN ELISA assay detects endogenous FXN in the NHP heart. The baseline NHP FXN levels were subtracted (using PBS controls levels, mean 45.3 ng/mg obtained from 1 male/1 female). <b>(D)</b> Extrapolation from the NHP data of the dose-dependent levels of FXN that would be achieved in the heart of the average FA patient following administration of AAVrh.10hFXN. The mean human FXN levels quantified in the treated NHPs <b>(C)</b> added to the estimated human FA homozygote data (Fig. 1B) allow for the estimation of the theoretical efficacy of the AAVrh.10hFXN vector dosing. The vector-derived hFXN levels observed in NHP (<i>red bars</i>) were added to the hFXN level baseline of 9.4 ng/mg estimated in FA homozygotes (<i>blue bars</i>). The <i>gray shading</i> represents the FXN level range seen in FA carriers (heterozygotes). NHP, nonhuman primate.</div> </figcaption> </figure> </div>  <div class="pswp figures-dialog" id="figures-dialog" tabindex="-1" role="dialog" aria-hidden="true" data-image-gallery-uid="article-figures" aria-label="Figures Dialog">  <div class="pswp__bg"></div>  <div class="pswp__scroll-wrap">  <div class="pswp__container"> <div class="pswp__item"></div> <div class="pswp__item"></div> <div class="pswp__item"></div> </div>  <div class="pswp__ui pswp__ui--hidden"> <div class="pswp__top-bar">  <div class="pswp__counter"></div> <button class="pswp__button pswp__button--close" title="Close (Esc)"></button> <button class="pswp__button pswp__button--share" title="Share"></button> <button class="pswp__button pswp__button--fs" title="Toggle fullscreen"></button> <button class="pswp__button pswp__button--zoom" title="Zoom in/out"></button>   <div class="pswp__preloader"> <div class="pswp__preloader__icn"> <div class="pswp__preloader__cut"> <div class="pswp__preloader__donut"></div> </div> </div> </div> </div> <div class="pswp__share-modal pswp__share-modal--hidden pswp__single-tap"> <div class="pswp__share-tooltip"></div> </div> <button class="pswp__button pswp__button--arrow--left" title="Previous (arrow left)"> </button> <button class="pswp__button pswp__button--arrow--right" title="Next (arrow right)"> </button> <div class="pswp__caption"> <div class="pswp__caption__center"></div> </div> </div> </div> </div> <div class="figure-dialog-caption"> <div class="figure-caption-link-container"> <a class="figure-caption-link" href="#">See this image and copyright information in PMC</a> </div> <div class="figure-caption-center" data-expand-title="click to show full caption" data-collapse-title="click to hide full caption"> </div> <button class="figure-caption-toggle-btn" aria-label="show full caption" data-expand-text="show full caption" data-collapse-text="hide full caption">  </button> </div> </div> <div class="similar-articles" id="similar"> <h2 class="title"> Similar articles </h2> <ul class="articles-list" id="similar-articles-list"> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/38600238/" ref="article_id=38600238&linksrc=similar_articles_link&ordinalpos=1" data-ga-category="similar_article" data-ga-action="38600238" data-ga-label=""> Expression and processing of mature human frataxin after gene therapy in mice. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Rojsajjakul T, Selvan N, De B, Rosenberg JB, Kaminsky SM, Sondhi D, Janki P, Crystal RG, Mesaros C, Khanna R, Blair IA.</span> <span class="docsum-authors short-authors">Rojsajjakul T, et al.</span> <span class="docsum-journal-citation full-journal-citation">Sci Rep. 2024 Apr 10;14(1):8391. doi: 10.1038/s41598-024-59060-0.</span> <span class="docsum-journal-citation short-journal-citation">Sci Rep. 2024.</span> <span class="citation-part">PMID: <span class="docsum-pmid">38600238</span></span> <span class="free-resources spaced-citation-item citation-part">Free PMC article.</span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/32646255/" ref="article_id=32646255&linksrc=similar_articles_link&ordinalpos=2" data-ga-category="similar_article" data-ga-action="32646255" data-ga-label=""> Stress-Induced Mouse Model of the Cardiac Manifestations of Friedreich's Ataxia Corrected by AAV-mediated Gene Therapy. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Salami CO, Jackson K, Jose C, Alyass L, Cisse GI, De BP, Stiles KM, Chiuchiolo MJ, Sondhi D, Crystal RG, Kaminsky SM.</span> <span class="docsum-authors short-authors">Salami CO, et al.</span> <span class="docsum-journal-citation full-journal-citation">Hum Gene Ther. 2020 Aug;31(15-16):819-827. doi: 10.1089/hum.2019.363.</span> <span class="docsum-journal-citation short-journal-citation">Hum Gene Ther. 2020.</span> <span class="citation-part">PMID: <span class="docsum-pmid">32646255</span></span> </div> </div> </li> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/38038720/" ref="article_id=38038720&linksrc=similar_articles_link&ordinalpos=3" data-ga-category="similar_article" data-ga-action="38038720" data-ga-label=""> A modified mouse model of Friedreich's ataxia with conditional <em>Fxn</em> allele homozygosity delays onset of cardiomyopathy. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Perfitt TL, Huichalaf C, Gooch R, Kuperman A, Ahn Y, Chen X, Ullas S, Hirenallur-Shanthappa D, Zhan Y, Otis D, Whiteley LO, Bulawa C, Martelli A.</span> <span class="docsum-authors short-authors">Perfitt TL, et al.</span> <span class="docsum-journal-citation full-journal-citation">Am J Physiol Heart Circ Physiol. 2024 Feb 1;326(2):H357-H369. doi: 10.1152/ajpheart.00496.2023. 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J Neurochem 2013;126(Suppl. 1):43–52; doi: 10.1111/jnc.12220 - <a class="reference-link" href="https://doi.org/10.1111/jnc.12220" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="10.1111/jnc.12220" > DOI </a> - <a class="reference-link" href="/23859340/" ref="linksrc=references_link&ordinalpos=2" data-ga-category="reference" data-ga-action="23859340" > PubMed </a> </li> </ol> </li> <li> <ol class="references-and-notes-list"> <li class="skip-numbering" value="1"> Anzovino A, Lane DJ, Huang ML, et al. . Fixing frataxin: ‘Ironing out’ the metabolic defect in Friedreich's ataxia. Br J Pharmacol 2014;171(8):2174–2190; doi: 10.1111/bph.12470 - <a class="reference-link" href="https://doi.org/10.1111/bph.12470" ref="linksrc=references_link&ordinalpos=1" data-ga-category="reference" data-ga-action="10.1111/bph.12470" > DOI </a> - <a class="reference-link" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC3976629/" ref="linksrc=references_link&ordinalpos=2" data-ga-category="reference" data-ga-action="PMC3976629" > PMC </a> - <a class="reference-link" href="/24138602/" ref="linksrc=references_link&ordinalpos=3" data-ga-category="reference" data-ga-action="24138602" > PubMed </a> </li> </ol> </li> </ol> <div class="actions-bar"> <button class="show-all" ref="linksrc=show_all_references_link" aria-controls="top-references-list-1" data-next-page-url="/37166361/references/" data-ga-category="reference" data-ga-action="show_more" > Show all 31 references </button> </div> </div> </div> </div> <div id="publication-types" class="publication-types keywords-section"> <h2 class="title"> Publication types </h2> <ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Research Support, N.I.H., Extramural" tabindex="0" aria-controls="keyword-actions-publication-types-0" aria-expanded="false" data-pinger-ignore> Research Support, N.I.H., Extramural </button><div id="keyword-actions-publication-types-0" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Research Support, N.I.H., Extramural"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Research+Support%2C+N.I.H.%2C+Extramural%22%5Bpt%5D&sort=date&sort_order=desc" data-href="/?term=%22Research+Support%2C+N.I.H.%2C+Extramural%22%5Bpt%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="Research 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data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Animals"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Friedreich Ataxia* / genetics" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-1" aria-expanded="false" data-pinger-ignore> Friedreich Ataxia* / genetics </button><div id="keyword-actions-mesh-terms-major-1" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Friedreich Ataxia* / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Friedreich+Ataxia%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22Friedreich+Ataxia%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc" 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class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Humans"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Humans"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Humans" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Humans"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Humans"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Humans"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button 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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Mice, Knockout" tabindex="0" aria-controls="keyword-actions-mesh-terms-8" aria-expanded="false" data-pinger-ignore> Mice, Knockout </button><div id="keyword-actions-mesh-terms-8" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Mice, Knockout"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Mice%2C+Knockout%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Mice%2C+Knockout%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Mice, Knockout"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Mice, Knockout"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Mice%2C+Knockout" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Mice, Knockout"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Mice, Knockout"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Mice, Knockout"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li></ul> </div> <div id="substances" class="substances keywords-section"> <h2 class="title"> Substances </h2> <ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Iron-Binding Proteins" tabindex="0" aria-controls="keyword-actions-substances-0" aria-expanded="false" data-pinger-ignore> Iron-Binding Proteins </button><div id="keyword-actions-substances-0" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Iron-Binding Proteins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Iron-Binding+Proteins%22%5Bnm%5D&sort=date&sort_order=desc" data-href="/?term=%22Iron-Binding+Proteins%22%5Bnm%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&keyword="Iron-Binding Proteins"[nm]" data-ga-category="search" data-ga-action="substance" data-ga-label="Iron-Binding Proteins"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Iron-Binding+Proteins%22" data-ga-category="search_mesh" data-ga-action="substance_link" data-ga-label="Iron-Binding Proteins"> Search in MeSH </a></li><li><a class="add-to-search-link 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Identification of Safe and Effective Intravenous Dose of AAVrh.10hFXN to Treat the Cardiac Manifestations of Friedreich's Ataxia - PubMed