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The advent of cerebrospinal fluid (CSF) and skin real-time quaking-induced conversion (RT-QuIC), coupled with high-specificity brain MRI, has enabled robust ante-mortem diagnostic support for CJD, which was previously only definitively established post-mortem. Yet no disease-modifying therapy exists. Drawing on a molecularly supported case of sporadic CJD, this Perspective argues that the widening gap between diagnostic precision and therapeutic impotence is not merely a failure of prion medicine\u2014it is a stress test for the entire rare-disease ecosystem. We examine how this diagnostic triumph creates an unprecedented opportunity for presymptomatic intervention, ultra-adaptive clinical trials, and synergistic combination therapies, and we propose a strategic roadmap to ensure that the next patient diagnosed within hours has a chance, however slim, of a different outcome.<\/jats:p>","DOI":"10.1177\/09226028261488180","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:13:27Z","timestamp":1789496007000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Creutzfeldt\u2013Jakob Disease in the Era of Diagnostic Triumph and Therapeutic Defeat: A Perspective from the Bedside"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3043-2479","authenticated-orcid":false,"given":"Xiaoyan","family":"Zhang","sequence":"first","affiliation":[{"name":"Peking University Third Hospital Qinhuangdao Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5314-5099","authenticated-orcid":false,"given":"Yao","family":"Tian","sequence":"additional","affiliation":[{"name":"Peking University Third Hospital Qinhuangdao Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5938-4806","authenticated-orcid":false,"given":"Changren","family":"Li","sequence":"additional","affiliation":[{"name":"Peking University Third Hospital Qinhuangdao Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9388-3100","authenticated-orcid":false,"given":"Muyang","family":"Li","sequence":"additional","affiliation":[{"name":"Peking University Third Hospital Qinhuangdao Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1651-9519","authenticated-orcid":false,"given":"Zhenxing","family":"Wang","sequence":"additional","affiliation":[{"name":"Peking University Third Hospital Qinhuangdao Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2294"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.1319"},{"issue":"1","key":"e_1_3_3_4_1","first-page":"3298","article-title":"Sporadic Creutzfeldt-Jakob disease: Real-time quaking induced conversion (RT-QuIC) assay represents a major diagnostic advance","volume":"65","author":"Cazzaniga F. 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