Most registered human trials ask about safety before efficacy. PrProfile (ION717, 85 participants, active and not recruiting, primary completion estimated April 2027) has adverse events to Week 33 as its primary outcome and percent change in CSF PrP up to Week 33 as a secondary outcome. PRiSM (45 estimated) has adverse events to Week 24 as primary. The ALN-6457 trial (60 estimated, not yet recruiting) lists plasma neurofilament light chain through Week 130 as a primary outcome. Which marker, if any, predicts clinical benefit has not been established in the sources read.
Preclinical programmes carry their own stated doubts. A 2012 review by Liang and Kong found ADAM8 to be the primary alpha-cleavage protease for PrP in muscle, while the authors’ preliminary and unpublished brain data suggested a less prominent role in brain. This is relevant to any strategy that relies on ADAM8 in neurons. The pages below set out questions by area: biology, diagnostics, therapeutics, trials and endpoints, genetics and prevention, epidemiology, zoonotic risk and care and access. Related: mechanisms, prevention and the Research hub.
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Sources for this page
- ClinicalTrials.gov NCT06153966: PrProfile, a study of ION717
- ClinicalTrials.gov NCT07444580: PRiSM, PrP-targeting siRNA safety and mechanism study
- ClinicalTrials.gov NCT07832370: a trial of ALN-6457 in symptomatic prion disease
- Liang J, Kong Q. Alpha-cleavage of cellular prion protein. Prion 2012 (PMC3510859)