The Generative Brain

ES-QuIC (enhanced sensitivity endpoint QuIC, deer mouse substrate)

Detects: seeding activity of misfolded prion protein. Sample: cerebrospinal fluid by lumbar puncture, 15 microlitres per reaction in the published protocol. Stage: research assay from one national laboratory, published January 2026, under parallel evaluation against the accredited Canadian test rather than in routine service. ES-QuIC is the Canadian national prion laboratory's endpoint QuIC with the hamster substrate swapped for recombinant prion protein of the North American deer mouse. The point of the change is the group of cases conventional QuIC misses: inherited forms such as D178N, and atypical sporadic subtypes. On a single retrospective panel it reported higher sensitivity than both the Canadian EP-QuIC service assay and second generation IQ-CSF RT-QuIC, at unchanged specificity. Information only, not advice.

Key facts

  • ES-QuIC is endpoint QuIC run with full-length recombinant prion protein, residues 23 to 230, from the North American deer mouse, Peromyscus maniculatus, expressed in E. coli and refolded on column; the name is given by the authors in the primary paper.
  • On a panel of 116 cases it reported 96.6 percent sensitivity and 100 percent specificity; the abstract gives 111 of 116 (which is 95.7 percent) while the table counts give 112 of 116 (96.6 percent), and the control count differs within the paper (35 in the abstract, 71 in Table 1, 75 in the text for the hamster assay), against 87.1 percent for the standard hamster EP-QuIC and 72.4 percent for IQ-CSF RT-QuIC on the same samples.
  • The panel was diagnostic CSF submitted between 2014 and 2024: 61 sporadic CJD (MM1 26, MV1 7, VV2 10, VV1 5, MV2 3, MM2 2), 50 cases the abstract calls inherited (see the next fact) and 5 VPSPr, with some samples supplied by the US National Prion Disease Pathology Surveillance Center.
  • The subtype lists in this entry do not add up to the group totals: the sporadic subtypes listed sum to 53 of 61, and the genetic subtypes below sum to 40 of the 50 cases the abstract calls inherited. A full text re-read (C-106, moderate confidence, tables read from XML) found that the 50 are 40 genetic cases plus 10 atypical sporadic cases grouped with them in Table 2.
  • The genetic group was FFI D178N 13, GSS P102L 10, E200K 7, octapeptide repeat insertions 4, V210I 2, D178N genetic CJD 1, V180I 1, P105S 1 and A117V 1.
  • The clearest gain was in D178N fatal familial insomnia: 12 of 13 detected, against 4 of 13 by hamster EP-QuIC and none of 13 by IQ-CSF RT-QuIC.
  • All 10 GSS P102L and all 5 VV1 sporadic cases were detected; VPSPr improved least, with 3 of 5 positive and 1 indeterminate; the single V180I case was detected only by IQ-CSF and missed by both endpoint assays.
  • Published conditions: 15 microlitres of CSF in a 100 microlitre reaction, 42 degrees, 900 rpm shaking in a ThermoMixer, fluorescence read at baseline and again at 50 to 66 hours, positive threshold set at baseline plus 20 standard deviations.
  • The assay is not the Canadian reference test. The national laboratory service listing names only PRNP sequencing and the accredited CSF EP-QuIC test, with no mention of ES-QuIC or a deer mouse substrate.
  • The two 2026 papers describe the transition differently: the January paper says the group is just beginning to use the deer mouse substrate routinely for diagnostic testing in Canada, while the September review calls it a preliminary parallel evaluation alongside EP-QuIC on routine diagnostic CSF.
  • The authors ask for independent laboratory validation, inter-laboratory reproducibility work, protocol harmonisation and larger prospective cohorts with clinical and neuropathological follow-up before the assay enters standard workflows.
  • The substrate choice follows the same group's work transmitting sporadic CJD and chronic wasting disease into deer mice, published April 2025, which found 100 percent attack rates for both and distinct seeding kinetics.
  • It sits at the end of a Canadian endpoint QuIC line: EP-QuIC published in 2016 with sensitivity 98 and specificity 91 percent, a ThermoMixer version in 2018, and a 2020 prospective study in which the positive predictive values of EP-QuIC, 14-3-3 gamma and total tau were 96, 68 and 66 percent.
  • Ethics approval came from the Health Canada and Public Health Agency of Canada Research Ethics Board (references 2009-036P and 2017-009P); the work was funded by the Public Health Agency of Canada, with collection and storage of the US samples funded through the surveillance center under CDC award 1NU38CK000486; the authors report no conflicts.

Timeline

  1. 2016EP-QuIC published from the national laboratory in Winnipeg as a high-throughput antemortem CSF test.
  2. 2018ThermoMixer-aided EP-QuIC published, shortening time to result.
  3. 2020Prospective Canadian study of EP-QuIC against 14-3-3 and total tau published.
  4. 2025Deer mouse transmission study of sporadic CJD and chronic wasting disease published, the groundwork for the substrate switch.
  5. 2026ES-QuIC paper published online in Annals of Neurology.
  6. 2026Print issue, Annals of Neurology 99(5):1303-1314.
  7. 2026Review in Frontiers in Neuroscience sets out the case for ES-QuIC and reports parallel evaluation against EP-QuIC.
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