- The PRNP geneSwitch off or edit the gene that makes the protein.
- Base editing
- Epigenetic editing
- Zinc finger repressors
- The RNA messageLower how much protein the cell makes.
- ION717
- PrP siRNA
- The prion proteinBind the protein or change how cells handle it.
- PRN100 antibody
- Small molecules
- The brain's responseSupport the cells reacting to the damage.
- Early ideas
A simplified view: none of these is a proven treatment. ALN-6457 also targets PRNP, but the trial registry does not state its drug type, so it is not placed here.
- Early research
- First human studies
- Clinical trials
- Approved
A simplified view. No treatment is proven yet. See the Atlas for each record and its date.
This page groups the therapies in the Atlas by approach. Most are in laboratory or early clinical stages. An entry here means a team is studying the approach. It does not mean the approach works, and it does not mean you can get it. Doctors and trial teams can say who may take part in a study.
Is there a treatment?
Not yet in the sense of a treatment shown in people to be both safe and effective. Care today is supportive. Researchers are testing several approaches, and the first human trials of drugs that lower prion protein are under way.
Which approaches are in the Atlas?
| Entry | What it covers |
|---|---|
| PrP-lowering | Drugs that reduce the amount of prion protein the body makes |
| Gene and epigenetic editing | Changes to the PRNP gene or its switches |
| Antibodies | Antibodies that bind prion protein |
| Small molecules | Drugs taken by mouth or injection that act on prion protein |
| Repurposed and stopped | Existing drugs tried for prion disease, and programs that ended |
| ADAM8 gene therapy | A preclinical gene therapy program |
| ALN-6457 | A siRNA program that lowers PrP |
| PRN100 | An anti-prion protein antibody |
| Base editing | A gene editing approach |
What is in clinical trials now?
As of July 2026, the Prion Alliance reported two PrP-lowering trials under way, one using a siRNA and one an antisense oligonucleotide. Results for the antisense trial are not expected before 2027, according to the company. The CJD Foundation lists the programs by sponsor and notes that several are preclinical or not enrolling. Trial details, with sponsor-stated eligibility and dates, are on Trials.
What is PrP-lowering?
Prion disease needs normal prion protein, called PrP, to spread. Lowering PrP is intended to leave less for misfolded protein to act on. In prion-infected mice, lowering PrP slowed disease and extended survival. Mouse results do not show what happens in people, which is why the human trials are running.
What happened to the PRN100 antibody?
The CJD Foundation lists PRN100, an antibody against prion protein, as not currently enrolling. It describes a first-in-human program that ran under a Specials Licence, which lets a doctor use an unlicensed drug for one patient and is not a regulated trial. The PRN100 entry gives the details.
Where does this connect to testing?
Measuring whether a drug works depends on reliable tests, which are on Tests and assays. The Atlas home lists the other sections.
Explore
- ADAM8-based gene therapy (Kong, NPDPSC)The idea is to deliver the gene for ADAM8, an enzyme that cuts the prion protein (PrP) in a way that inactivates it, using a viral vector that crosses
- ALN-6457 (siRNA, Regeneron)ALN-6457 (also named ALN-PRNP) is Regeneron's PRNP-targeting drug for symptomatic prion disease, inferred but not confirmed to come from the Regeneron
- Antibody therapiesAntibody therapies for prion disease in the Atlas: one humanised antibody, PRN100, given to six patients in 2022 and not currently enrolling.
- 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.
- Base editing of PRNP (split dual-AAV)One-time adenine or cytosine base editing of PRNP delivered by AAV to install a stop codon (R37X) and permanently lower PrP.
- CHARM epigenetic editor (zinc finger guided DNA methylation)CHARM (Coupled Histone tail for Autoinhibition Release of Methyltransferase) is a compact epigenetic editor that uses a zinc finger protein to recruit
- Dominant-negative protein-based gene therapy (Castilla)Instead of lowering the brain's own prion protein, this approach adds an engineered version of the protein that does the normal job but cannot misfold
- Doxycycline prevention in FFI carriers (Italy)Anti-prion activity in lab models; used preventively in pre-symptomatic carriers.
- Gate Bioscience oral small-molecule Molecular GateGate Bioscience is developing an oral, brain-penetrant small molecule that stops cells from exporting PrP and sends it for destruction, with the goal
- Gene and epigenetic editingGene and epigenetic editing approaches to lower prion protein, tested in mice and not yet in people: CHARM, base editing and zinc finger repressors.
- Downstream glial and neuroinflammation targetsInstead of lowering the prion protein, this idea targets the brain's own support cells that react to prion damage.
- GPNMB as a therapeutic target (Aguzzi, Zurich)GPNMB is made by a distinctive group of microglia, the brain's immune cells, that appear in prion-infected mouse brains where nerve cells are dying.
- NSC500 (pentamer formyl thiophene acetic acid), EU orphan designated anti-prion compoundNSC500 is the sponsor code under which NeuroScios GmbH, a small central nervous system drug development company at St.
- Preimplantation genetic testing (PGT) for PRNP variants, including exclusion PGTPGT is done during in vitro fertilisation: cells from early embryos are tested and only embryos that did not inherit the familial PRNP variant are tra
- PMSA, Protein Misfolding Shaking Amplification for generating bona fide recombinant prionsPMSA is a laboratory method, not a treatment or a test offered to anyone.
- Zinc tetracationic porphyrin anti-prion compound (Mario Negri)This is a preclinical anti-prion compound from the Laboratory of Prion Neurobiology at the Istituto di Ricerche Farmacologiche Mario Negri IRCCS in Mi
- PPI-FIT folding intermediate targeting anti-prion compounds (University of Trento)This is a preclinical drug discovery line from the Dulbecco Telethon Laboratory of Prions and Amyloids at CIBIO, University of Trento, led by Emiliano Biasini.
- PrP-lowering antisense oligonucleotide (ION717)ION717 is an antisense oligonucleotide that lowers prion protein (PrP) production, given by lumbar puncture.
- PrP-lowering therapiesPrP-lowering drugs reduce the prion protein the brain makes. Two are in early human trials, an antisense drug and a siRNA, with no results yet.
- PrP-lowering divalent siRNA (PRiSM drug candidate 2439-s4 / exNA)PrP-siRNA (2439-s4) is a divalent siRNA developed by the Broad and UMass Chan that lowers PrP; it is in the PRiSM first-in-human trial.
- Brain-penetrant small molecule lowering PrPC (Toronto)This approach tries to lower the cell-surface prion protein with a tablet instead of an injected drug.
- Repurposed and stopped approachesExisting drugs tried for prion disease, including flupirtine, pentosan polysulfate, quinacrine and doxycycline, and what the completed studies found.
- Repurposed small molecules: quinacrine, doxycycline, flupirtine, pentosan polysulphateBefore any prion-specific drug existed, doctors tried existing medicines that blocked prion formation in cells or looked safe in the brain.
- Serpin (SERPINA3 and SerpinA3n) inhibition as a non-PrP-targeted anti-prion strategy (ARN1468, SISSA and IIT)Most prion drug work aims at the prion protein itself, either lowering the normal form or blocking its conversion.
- Small moleculesSmall-molecule approaches to lower prion protein: Gate Bioscience Molecular Gates and Trento compounds, both preclinical, none tested in people.
- AAV zinc finger repressor of PRNP (Sangamo with the Broad)A one-time intravenous AAV zinc finger repressor of PRNP (ST-506) developed by Sangamo with the Broad.