The Generative Brain

OBSERVE (NCT05124392): biomarkers in individuals at risk for prion disease

MGH-based observational cohort of people at risk for genetic prion disease (known carriers, 50/50-risk relatives who may not know their status, and controls), with annual visits in Charlestown. Its published findings define when biomarkers change before onset: CSF RT-QuIC turned positive in E200K carriers before symptoms, and other markers stayed normal.

Status as of 2026-10-16. Please check the study registry for the latest position.

Key facts

  • Lead sponsor Massachusetts General Hospital with the Broad Institute as collaborator; principal investigator Steven E. Arnold; one site (Alzheimer's Clinical and Translational Research Unit, Charlestown).
  • Design: annual visits with a medical exam, blood draws, cognitive tests and questionnaires, spinal fluid collection and an optional MRI; travel support and a stipend are provided.
  • Eligibility: history of probable or definite prion disease in a biological parent and other relatives; ability to consent; MRI screening applies to known carriers only; excluded are recent substance dependence, significant systemic illness and pregnancy; ages 18 to 85; target enrolment 150; participants need not know their genetic status.
  • Origin: sponsored by Prion Alliance from July 2017 with donations; the original quota of 20 participants was extended toward 60 in 2018.
  • By the December 2023 data freeze the cohort had 62 people (41 PRNP carriers and 21 controls) and more than 150 CSF and plasma samples; funders were Prion Alliance, the CJD Foundation, an NCATS grant and Ionis.
  • Results (Neurology 2024): CSF RT-QuIC seeding appeared in 3 asymptomatic E200K carriers who later converted and died, within 4 disease onsets over 6 years, suggesting seeding may be the earliest detectable change in E200K carriers.
  • RT-QuIC is sensitive in E200K and sporadic disease but usually stays negative in other genetic variants even after symptoms start; asymptomatic carriers were generally negative on other markers, so new prodromal markers are needed for other subtypes.
  • The earlier 2020 cohort report (27 carriers, 16 controls): RT-QuIC negative in 22 of 23 carriers; tau and NfL did not separate carriers from controls.
  • The registry completion date is estimated 2027-06-01; the record was last updated 2026-04-22.

Timeline

  1. 2017Prion Alliance announces the study.
  2. 2017Registry start date.
  3. 2018Plan to expand from 20 toward 60 participants.
  4. 2020BMC Medicine report on 27 carriers and 16 controls.
  5. 2023Second data freeze reported (62 participants).
  6. 2024Neurology paper reports four conversions over six years.
  7. 2026Registry record last updated.
  8. 2027Estimated study completion.
Sources for this page