Vallabh SM et al. 2020, Cerebrospinal fluid and plasma biomarkers in individuals at risk for genetic prion disease (BMC Med 18:140, PMID 32552681, doi 10.1186/s12916-020-01608-8)

A single-site cohort study from Massachusetts General Hospital that looked at which fluid biomarkers could serve as trial endpoints in people who carry a high-risk PRNP variant but have no symptoms. At the group level, CSF prion protein was very stable on repeat sampling, while RT-QuIC seeding and the neuronal damage markers tau and NfL did not separate carriers from controls. The authors drew the conclusion that CSF PrP is a credible pharmacodynamic marker for PrP-lowering drugs and that primary prevention designs look more tractable than secondary prevention. This summary rests on the abstract and registry records only; the full text was not read.

Key facts

  • The paper is Vallabh SM et al., BMC Medicine 2020, volume 18, article 140, published online 18 June 2020, with 18 authors, DOI 10.1186/s12916-020-01608-8, PMID 32552681 and PMCID PMC7302371.
  • The stated problem is that randomising presymptomatic variant carriers to a clinical endpoint is numerically infeasible, so the cohort was set up to evaluate biomarker endpoints for future trials.
  • The cohort comprised 27 presymptomatic PRNP mutation carriers and 16 matched controls, sampled at Massachusetts General Hospital.
  • Measures were total CSF PrP, RT-QuIC seeding activity, total tau and neurofilament light chain, in CSF and blood.
  • CSF PrP was stable on retest 2 to 4 months apart, with a mean coefficient of variation of about 7%.
  • RT-QuIC was negative in 22 of 23 carriers tested.
  • Tau and NfL did not differ significantly between carriers and controls in either CSF or plasma.
  • A pilot longitudinal component ran 10 to 20 months.
  • The authors propose CSF PrP as a pharmacodynamic readout and surrogate marker for PrP-lowering therapy, and suggest that primary prevention trials may be more tractable than secondary prevention trials.
  • The article is open access under a CC BY licence; Crossref lists funders as Prion Alliance, CJD Foundation, the Broad Institute Next Gen Fund, NSF (GRFP), NIAID (F31) and NCATS (R21).
  • Scout note: the queue entry's reason says the paper gives "baseline biomarker data"; the abstract also covers test-retest and a pilot longitudinal arm, and the citation details in the queue (BMC Med 18:140, PMID, DOI) match PubMed, Europe PMC and Crossref.

Timeline

  1. 2020Funding acknowledged from the Prion Alliance, CJD Foundation, Broad Institute and US federal grants (NSF, NIAID, NCATS).
  2. 2020Article published online in BMC Medicine (issue dated June 2020).

People

Last checked 1 November 2026

Sources for this page