01
Lowering the normal prion protein
The disease process depends on the body's own prion protein (PrP). Several strategies ask a simple question: if there is less normal PrP available, can the disease slow down?
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PrP is encoded by PRNP. Genetic evidence in animals shows that reducing PrP expression extends survival after prion infection, and heterozygous loss-of-function variants in humans appear tolerated. PrP-lowering is being pursued with RNA-targeting modalities delivered to the CNS.
02
siRNA
Small interfering RNA is a type of molecule that tells cells to make less of a specific protein. A PrP-targeting siRNA is now in a first-in-human safety study.
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Chemically modified, divalent siRNA designs have been developed for durable PrP knockdown in the CNS after intrathecal administration. The PRiSM study (NCT07444580) evaluates safety, tolerability, PK and PD in symptomatic adults.
03
Antisense oligonucleotides
Antisense oligonucleotides (ASOs) are another way to reduce production of a protein. They have been studied for prion disease in laboratory models and in early clinical work.
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PRNP-targeting ASOs extend survival in prion-infected mice, including when dosed after symptom onset. Human evaluation has been limited. Consult current literature and registries for the state of clinical development.
04
Biomarkers and diagnosis
Tests that detect the disease earlier and track how it changes over time. Better markers help doctors diagnose sooner and help trials measure whether a treatment is doing anything.
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RT-QuIC on CSF and other samples, total tau, neurofilament light chain, 14-3-3 and MRI (DWI/FLAIR patterns) support diagnosis. CSF PrP concentration is used as a target-engagement marker for PrP-lowering approaches.
05
Monitoring progression
Because CJD moves fast, research teams work on ways to measure decline precisely. This matters for patients, for families planning care, and for evaluating any experimental intervention.
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Clinical scales, serial fluid biomarkers and imaging are used to quantify progression. Natural history data in sporadic CJD is essential context for interpreting single-arm or small early-phase studies.