{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:43:49Z","timestamp":1771461829334,"version":"3.50.1"},"reference-count":19,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,10,15]],"date-time":"2022-10-15T00:00:00Z","timestamp":1665792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>ATTR amyloidosis comprises a spectrum of multiple clinical presentations, including, predominantly, neuropathy and cardiomyopathy. The common triggering pathogenic protein is misfolded transthyretin, a carrier protein that destabilizes misfolds and assembles into mature amyloid fibrils. The current management of ATTR amyloidosis includes the use of agents that stabilize TTR or attenuate its liver inducible production. Herein, we tested the hypothesis that a monoclonal antibody targeting the soluble oligomeric as well as the aggregated TTR would influence experimental neuropathy. We have shown that Ab-A, our previously described humanized IgG monoclonal antibody, dose-dependently ameliorates the toxicity to neurons triggered by misfolded TTR oligomers. Furthermore, the antibody that exhibits wide misTTR epitope recognition that includes the oligomeric and aggregated forms of the protein dose-dependently enhances the uptake of misfolded TTR to microglia, the resident predominant cells of the innate immune system within the CNS. These in vitro mechanistic properties of the antibody were corroborated by experimental in vivo data showing that the antibody rapidly clears human TTR amyloid extracts infiltrated to the sciatic nerves of rats. Thus, the monoclonal antibody targeting soluble and aggregated TTR is effective in experimental neuropathy, likely due its ability to act as a neuroprotective agent, as well its misTTR-mediated clearance via microglia.<\/jats:p>","DOI":"10.3390\/biology11101509","type":"journal-article","created":{"date-parts":[[2022,10,16]],"date-time":"2022-10-16T21:10:10Z","timestamp":1665954610000},"page":"1509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual Targeting of Soluble Oligomeric and Aggregated Transthyretin with a Monoclonal Antibody Ameliorates Experimental Neuropathy"],"prefix":"10.3390","volume":"11","author":[{"given":"Michael","family":"Fassler","sequence":"first","affiliation":[{"name":"Heart Center, Kaplan Medical Center, Rehovot, Hebrew University of Jerusalem, Jerusalem 91905, Israel"},{"name":"Cognyxx Ltd., Tel Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sagi","family":"Tshori","sequence":"additional","affiliation":[{"name":"Heart Center, Kaplan Medical Center, Rehovot, Hebrew University of Jerusalem, Jerusalem 91905, Israel"},{"name":"Research Authority, Kaplan Medical Center, Rehovot, Hebrew University of Jerusalem, Jerusalem 91905, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4688-2358","authenticated-orcid":false,"given":"Yaron","family":"Barac","sequence":"additional","affiliation":[{"name":"The Division of Cardiovascular and Thoracic Surgery, Rabin Medical Center, Petach Tikva 4941492, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawn E.","family":"Bowles","sequence":"additional","affiliation":[{"name":"Surgical Sciences Division, Department of Surgery, Duke University, Durham, NC 27710, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Benaim","sequence":"additional","affiliation":[{"name":"Heart Center, Kaplan Medical Center, Rehovot, Hebrew University of Jerusalem, Jerusalem 91905, Israel"},{"name":"Cognyxx Ltd., Tel Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"George","sequence":"additional","affiliation":[{"name":"Heart Center, Kaplan Medical Center, Rehovot, Hebrew University of Jerusalem, Jerusalem 91905, Israel"},{"name":"Cognyxx Ltd., Tel Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0022-2836(74)90291-5","article-title":"Structure of human plasma prealbumin at 2-5 A resolution. 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Disord.-Drug Targets"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1080\/13506129.2022.2052838","article-title":"Guidelines and new directions in the therapy and monitoring of ATTRv amyloidosis","volume":"29","author":"Ando","year":"2022","journal-title":"Amyloid"}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/11\/10\/1509\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:54:36Z","timestamp":1760144076000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/11\/10\/1509"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,15]]},"references-count":19,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["biology11101509"],"URL":"https:\/\/doi.org\/10.3390\/biology11101509","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,15]]}}}