Prion disease needs normal prion protein to spread, and animal studies suggest the body can do without most of it. PrP-lowering drugs act on the gene’s message so that less protein is made. In prion-infected mice, antisense oligonucleotides and divalent siRNA slowed disease and extended survival. The work began with a 2014 collaboration between Sonia Vallabh and Eric Minikel at the Broad Institute and Ionis.
Two drugs are in human trials. The Ionis antisense drug ION717 enrolled 56 symptomatic patients in 2024 and reopened in March 2026 with a third dosing regimen, and Ionis says public results are not expected before 2027. The PRiSM trial of a divalent siRNA, run through NIH NeuroNEXT, is recruiting. The Prion Alliance described it in July 2026 as enrolling only symptomatic patients, and the CJD Foundation page, with a statement dated 14 October 2026, lists a pre-symptomatic arm as now open. Check the sponsor or trial registry for current eligibility. The CJD Foundation also lists ALN-6457, a Regeneron siRNA program, in a trial for adults with symptomatic disease. No human safety and efficacy data exist yet for any of them.