The Generative Brain

Anti-PrP antibody PRN100 (UCL)

PRN100 is an antibody that binds the normal prion protein on cells, with the aim of stopping its conversion to the disease form. It was made by the MRC Prion Unit at UCL and given by intravenous infusion to six people with CJD in 2018 and 2019 as an individual-patient programme, not a trial. It looked safe and reached the spinal fluid and brain, but no patient's disease was halted and the data cannot show benefit. The drug batch is used up, the authors call for a Phase 2 trial, and a charity appeal for one was launched in November 2025. No registered trial was found. Information only.

Key facts

  • Mechanism and form: a fully humanised monoclonal antibody against cellular prion protein, made academically to industry standard and given intravenously.
  • Who and how: six patients with CJD were treated at UCLH between October 2018 and July 2019 under a Specials exemption, which lets a clinician use an unlicensed drug for one patient, not as a regulated trial.
  • Dosing: 4-hour infusions escalating from 1 up to 120 mg/kg every two weeks; reaching target levels took an average of 47 days, a long time in a fast disease; two patients stopped when the drug ran out.
  • Safety: no clinically significant side effects and no serious adverse events; brain tissue examined after death showed no toxicity.
  • Brain exposure: CSF concentrations rose above target, with peak CSF levels of 16 to 132 nM, at least about 0.1 percent of the serum level; post-mortem brain data came from one patient.
  • Efficacy: progression was not halted or reversed in any patient; scores appeared to stabilise for periods in several while CSF levels were in range, which the authors call preliminary; overall survival and progression looked no different from matched historical controls.
  • Limits stated by the authors and others: six patients, historical controls, no randomisation, a single exhausted drug batch, and research sampling restricted to leftover clinical samples.
  • The authors recommend a larger regulated trial in patients at the earliest clinical stage and possibly later studies in healthy carriers of pathogenic PRNP variants or people exposed to prions through medical treatment.
  • Preclinical background: the parent mouse antibody ICSM18 delayed disease when given before infection reached the brain and did not help once infection was in the brain.
  • Where it stands now: no registration of a Phase 2 trial was found; the Cure CJD Campaign launched a 9 million pound appeal in November 2025 to fund one, and the CJD Foundation lists PRN100 as not currently enrolling.
  • Landscape: the Prion Alliance noted in July 2026 that the two PrP-lowering clinical trials underway use a siRNA and an antisense oligonucleotide and that no treatment has human safety and efficacy data yet; the antibody is not among the active trials on the foundation index.

Timeline

  1. 2003Mouse study of the parent antibody ICSM18 published.
  2. 2018First PRN100 dosing at UCLH under a Specials exemption.
  3. 2019Last of the six patients starts treatment.
  4. 2022Lancet Neurology paper published.
  5. 2022UCL and independent commentary released.
  6. 2025Cure CJD Campaign launches a 9 million pound appeal for a Phase 2 trial.
  7. 2026Prion Alliance update lists only siRNA and antisense trials as active PrP-lowering programs.
  8. 2026CJD Foundation drug development page lists PRN100 as not currently enrolling.
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