Mead S et al. 2022, Prion protein monoclonal antibody (PRN100) therapy for Creutzfeldt-Jakob disease, first-in-human treatment programme (Lancet Neurol 21:342-354, PMID 35305340)

This is the peer-reviewed report of the PRN100 programme at the National Prion Clinic and MRC Prion Unit in London, in which a humanised antibody against cellular prion protein was given by infusion to six people with probable CJD under a Specials Licence. The authors found it safe at high doses and able to reach the brain at target levels in four patients, but disease still progressed in every patient and six treated patients cannot show whether it changes the course of disease. They conclude that a regulated trial in the earliest clinical stages is warranted. The article is open access and was published online on 16 March 2022, in the April 2022 issue. Information only, not medical advice.

Key facts

  • Bibliographic record: 21 authors led by Simon Mead with John Collinge as last and corresponding author, Lancet Neurology 2022, volume 21, issue 4, pages 342 to 354, DOI 10.1016/S1474-4422(22)00082-5, PMID 35305340.
  • Europe PMC counted 80 citing papers on 1 November 2026.
  • Design: six patients with probable CJD, five sporadic and one iatrogenic, who were not in the terminal stage, started treatment between 9 October 2018 and 31 July 2019 at the UCLH Clinical Research Facility.
  • The legal route was an NHS treatment under a Specials Licence with hospital governance, not a research study; three patients consented themselves and the Court of Protection determined legality for the other three.
  • Dosing was by intravenous infusion every two weeks with escalation to 80 and then 120 mg/kg, and the treatment limit was the single available batch of drug product.
  • Safety: no clinically significant adverse reactions were seen, and neuropathology in the two patients who had an autopsy showed no sign of cytotoxicity.
  • Brain access: the 50 nM CSF target was reached in four patients after 22 to 70 days, a mean of 47 days, and drug concentration was measured in one post-mortem brain.
  • Efficacy: all patients declined; scale scores appeared to stabilise for periods in three patients while CSF drug levels were at target, but a linear mixed model against matched natural history controls was not significant and the authors say the numbers are too small to judge effect.
  • One autopsy showed altered disease-associated PrP staining compared with untreated cases, which the authors read as evidence of target engagement, with no amyloid-related imaging abnormalities seen in any patient.
  • Proposed next step: a regulated phase 2 in patients at the earliest clinical stage with dose escalation to target CSF levels within 48 to 72 hours, which natural history modelling suggests could be run with about 50 patients, followed by prophylaxis studies in PRNP mutation carriers or exposed people.
  • Funding: Cure CJD Campaign, the NIHR UCLH Biomedical Research Centre, the Jon Moulton Charitable Trust and the UK MRC; Collinge declares being a director and shareholder of D-Gen, which owns intellectual property relating to PRN100.

Timeline

  1. 2018First PRN100 treatment started, on 9 October 2018 per the paper.
  2. 2019Last of the six patients started treatment, by 31 July 2019.
  3. 2022Paper published online at 23:30 UK time with a UCL news release.
  4. 2022Printed in Lancet Neurology volume 21 issue 4.

People

Last checked 1 November 2026

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