PrP-targeting siRNA safety and mechanism in people with prion disease
Official title: An Open-label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered PrP-siRNA in Adults Diagnosed With Symptomatic Prion Disease and in Pre-symptomatic Adults at Genetic Risk for Prion Disease.
Run by Broad Institute of MIT and Harvard · NCT07444580 · Data updated 2026-11-12
This trial will test whether a single spinal (intrathecal) dose of PrP-targeting siRNA is safe and changes disease-related markers in people with symptomatic prion disease.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years and up |
| Sex | All |
| Enrollment | 45 (estimated) |
| Sponsor | Broad Institute of MIT and Harvard Academic / other |
| Locations | 5 sites (Boston, Massachusetts and 4 other locations) |
| Status | Recruiting |
| Started | May 15, 2026 |
| Main results expected | August 14, 2029 |
| Study ends | August 14, 2029 |
| Registry record updated | October 16, 2026 |
| Trial ID | NCT07444580 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates are people with clinically manifested prion disease meeting CDC criteria and confirmed by a positive CSF RT-QuIC or PRNP genetic test, with no more than moderate functional impairment (MRC-PDRS ≥15) and an available study partner.
✕Probably not a fit
People who are pregnant, have a contraindication to lumbar puncture, have functional impairment beyond the study limit, or recently participated in another prion trial are unlikely to be eligible or to benefit from this protocol.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This first-in-human, open-label, single-ascending-dose study gives one intrathecal dose of PrP-siRNA to participants with symptomatic prion disease and follows them for 24 weeks to monitor safety, tolerability, pharmacokinetics, and pharmacodynamic effects. Multiple dose levels will be tested sequentially, with a screening period of up to two weeks prior to dosing. An observational arm will follow participants who do not receive the investigational drug for eight weeks after baseline. Key endpoints include adverse events, CSF and blood drug levels, and biomarkers of PrP biology.
Why it matters
Potential benefit: If successful, the treatment could lower pathogenic prion protein levels in the central nervous system and potentially slow or stabilize disease progression.
How similar studies have gone: This is a novel first-in-human approach for prion disease; PrP-lowering strategies have shown benefit in animal models but human data are very limited.
Who can join: the full rules
Show full inclusion / exclusion criteria
Key inclusion criteria for symptomatic patients: 1. clinically manifested symptoms of prion disease, in the opinion of the investigator 2. a diagnosis of probable prion disease according to CDC criteria 3. a positive CSF RT-QuIC or PRNP genetic test 4. no more than moderate functional impairment as quantified by an MRC-PDRS score ≥15 5. availability of a caregiver to assist with study procedures Key inclusion criteria for pre-symptomatic patients: 1. lack of clinically manifested symptoms of prion disease, as demonstrated by an MRC Score of 20, a MoCA score between 24-30 inclusive, and a neurological exam with no clinically significant findings, in the opinion of the investigator 2. a PRNP genetic test indicating the presence of a highly penetrant genetic variant causal for prion disease Key exclusion criteria for all arms: 1. pregnancy or unwillingness to comply with the contraceptive requirements during the study period 2. contraindication to lumbar puncture 3. recent participation in a different prion disease clinical trial Additional inclusion and exclusion criteria apply and will be evaluated at screening.
Where it's running
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Massachusetts General Hospital
Boston, Massachusetts, United States Recruiting -
Mayo Clinic
Rochester, Minnesota, United States Recruiting -
Columbia University Medical Center
New York, New York, United States Recruiting -
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States Recruiting -
Vanderbilt University Medical Center
Nashville, Tennessee, United States Recruiting
Study contacts
- Principal investigator: Eric V Minikel, PhD — Broad Institute of MIT and Harvard
- Study coordinator: Broad Institute
- Email: priontrials@broadinstitute.org
- Phone: 617 714 7000
Similar studies
Other studies for the same condition or treatment. Recruiting studies are listed first.
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Teleneurology assessment for Creutzfeldt-Jakob disease
This study tests how well remote videoconference visits work to track adults with Creutzfeldt-Jakob disease over time, with input from a trusted study partner.
-
Prospective Registry for People at Risk of Genetic Prion Disease
This registry tests how PRNP gene mutations and related health changes unfold over time in adults who may develop genetic prion disease.
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Identifying biomarkers in individuals at risk for prion disease
This study is trying to find specific markers in people who might develop genetic prion diseases to see if they can help predict when the disease will start.
How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.