PrP-siRNA for Prion Diseases
(PRiSM Trial)
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial focuses on testing a new treatment called PrP-siRNA, a type of gene-silencing therapy, for individuals with prion diseases. Researchers aim to determine the treatment's safety and behavior in the body. One group of participants will receive the treatment, while another group will not, allowing for outcome comparisons. Ideal candidates have a prion disease diagnosis, experience symptoms, and retain some daily functioning ability. Participants must also have someone to assist with study tasks. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in humans.
Do I have to stop taking my current medications for the trial?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team to get a clear answer.
Is there any evidence suggesting that PrP-siRNA is likely to be safe for humans?
Research has shown that PrP-siRNA is still under study to determine its safety and effectiveness in humans. As this trial is among the first to test PrP-siRNA in individuals with prion diseases, limited information exists about its safety. Consequently, the researchers have not yet determined how well people can tolerate the treatment or if any major side effects occur.
In earlier studies with mice, a similar treatment showed promise. It reduced prion protein levels and extended the mice's lifespan. However, results in animals do not always predict outcomes in humans. As an early-stage trial, the primary goal is to gather safety information. Researchers will closely monitor participants for any negative effects.
Given the early phase of testing, knowledge about the treatment's safety remains limited. Participants should discuss potential risks and benefits with the trial team to make an informed decision.12345Why do researchers think this study treatment might be promising?
Unlike the standard of care for prion diseases, which typically involves supportive treatments aimed at managing symptoms, PrP-siRNA directly targets the genetic material responsible for producing the harmful prion proteins. This investigational treatment uses small interfering RNA (siRNA) to silence the PRNP gene, potentially preventing the formation of these damaging proteins at the source. Researchers are excited about PrP-siRNA because it represents a novel mechanism of action, offering hope for a disease-modifying approach rather than just symptomatic relief. Additionally, the unique intrathecal delivery method allows the treatment to reach the central nervous system directly, which is crucial for addressing prion diseases effectively.
What evidence suggests that PrP-siRNA might be an effective treatment for prion diseases?
This trial will compare an observational approach with a treatment approach using PrP-siRNA. Research has shown that PrP-siRNA targets the harmful proteins in prion diseases, which are fatal brain disorders. Studies in mice found that reducing these proteins can slow the disease's progression, though it does not stop or reverse it. PrP-siRNA blocks the genetic instructions that create these harmful proteins. Although no effective treatment for prion diseases currently exists, early research suggests that siRNA could be promising. Scientists believe it may help by lowering the levels of harmful proteins in the brain.23678
Who Is on the Research Team?
Eric V Minikel, PhD
Principal Investigator
Broad Institute of MIT and Harvard
Are You a Good Fit for This Trial?
This trial is for people who have symptoms of prion diseases (like CJD or FFI), confirmed by genetic or spinal fluid tests, and are still able to function moderately well. Participants need a study partner to help with procedures.Inclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive a single intrathecal dose of PrP-siRNA with dose levels of 50, 100, and 200 mg being sequentially evaluated
Follow-up
Participants are monitored for safety and effectiveness after treatment, with visits at Week 1, 2, 4, 8, 12, and 24
Observational
Participants in the observational arm undergo lumbar punctures and other study activities without receiving the investigational drug
What Are the Treatments Tested in This Trial?
Interventions
- PrP-siRNA
Trial Overview
The study is testing the safety and effects of an experimental drug called PrP-siRNA in patients with symptomatic prion diseases. Researchers will monitor how the body processes the drug and its impact on disease markers.
How Is the Trial Designed?
2
Treatment groups
Experimental Treatment
Active Control
In Arm 2, participants will be admitted to the clinical trial center and receive a single intrathecal dose of PrP-siRNA. Dose levels to be sequentially evaluated are 50, 100, and 200 mg. Patients will be discharged on Day 2 and then periodically return to the study center on an outpatient basis at Week 1, 2, 4, 8, 12 and 24 for safety monitoring and study activities through the 24 week follow up period.
In Arm 1, participants will undergo lumbar punctures and other study activities at baseline (Week 0) and at Week 4 and Week 8. Investigational drug will not be administered. We will prioritize enrollment in Arm 2; Arm 1 will be open to enrollment whenever Arm 2 is not open to enrollment.
Find a Clinic Near You
Who Is Running the Clinical Trial?
Broad Institute of MIT and Harvard
Lead Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)
Collaborator
Citations
PrP-targeting siRNA Safety & Mechanism Study
The purpose of this trial is to evaluate safety, tolerability, pharmacokinetics and pharmacodynamic impact of PrP-siRNA in symptomatic prion disease patients.
Developing Therapeutics for PrP Prion Diseases - PMC
The prototypical PrP prion diseases are invariably fatal, and the search for agents to treat them spans more than 30 years, with limited success.
Insights from Therapeutic Studies for PrP Prion Disease - PMC
Although an effective therapy for prion disease has not yet been established, many advances have been made toward understanding its pathogenesis.
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prionalliance.org
prionalliance.org/2026/04/22/first-in-human-trial-of-prp-sirna-in-symptomatic-prion-disease/First-in-human trial of PrP-siRNA in symptomatic prion ...
The goal of this clinical trial is to gather the very first human safety data to inform dosing and determine whether PrP-siRNA should advance to ...
sc-36318 - PrP siRNA (h)
Prion diseases, or transmissible spongiform encephalopathies (TSEs), are man- ifested as genetic, infectious or sporadic, lethal neurodegenerative disorders.
Susceptibility of cell substrates to PrPSc infection and safety ...
Abstract. Concerns over the potential for infectious prion proteins to contaminate human biologics and biotherapeutics have been raised from time to time.
Systemic Delivery of siRNA Down Regulates Brain Prion ...
After 12 days rectal mucosa administration of Aonys/PrP-siRNA in mice, we observed a decrease of about 28% of the brain PrPC level. The effect ...
In vivo base editing extends lifespan of a humanized ...
Misfolded PrP causes prion disease via a toxic gain of function, with 85% of cases caused by a spontaneous misfolding event of PrP, 15% caused ...
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