A diagnosis of probable prion disease according to CDC diagnostic criteria.
Positive CSF RT-QuIC, or a positive DNA test for a pathogenic PRNP mutation.
Symptoms of prion disease in the opinion of the Investigator.
Age ≥18 at the time of informed consent.
Meeting the criteria for prevention of pregnancy.
MRC-PDRS score ≥15 at the time of Screening
Provide written informed consent and be able and willing to comply with all study requirements (in the opinion of the Investigator), including travel to the Study Center, procedures, assessments, and visits. If the patient is not capable of providing consent, consent must be given by a legally authorized representative (LAR).
Study partner available to assist with study visits, who is sufficiently knowledgeable of the patient's condition to respond to inquiries about the patient for the duration of the trial.
Neurodegenerative disease such as Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis, Lewy Body Dementia, frontotemporal dementia, or Huntington's; untreated epilepsy; multiple sclerosis; or any other non-prion neurological condition that in the opinion of the investigator would pose a safety risk to the participant or confound interpretation of data from this trial.
Attempted suicide, suicidal ideation with a plan that required hospital admission and/or change in level of care within 12 months prior to Screening. For patients with (i) a suicide ideation score ≥ 4 on the C-SSRS within the last 12 months, or (ii) suicidal behaviors within the last 12 months (as measured by the answer “Yes” on any of the C-SSRS Suicidal Behavior Items), a risk assessment should be done by an appropriately qualified mental health professional (e.g., a Psychiatrist or licensed Clinical Psychologist) deemed by the Investigator to be at significant risk of suicide, major depressive episode, psychosis, confusional state or violent behavior are excluded.
Platelet count < 50,000/mm3 , INR>1.5, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than upper limit of normal, estimated glomerular filtration (eGFR) of <90 mL/min/1.73m^2 at screening, or any other clinically significant laboratory abnormality at Screening that, in the opinion of the Investigator, would render a patient unsuitable for inclusion. The Investigator may choose to repeat a laboratory test that they suspect to have failed due to a technical failure, at their own discretion.
Clinically significant vital sign or electrocardiogram (ECG) abnormality at Screening (including heart rate < 45 bpm; SBP < 90 mmHg; confirmed BP readings > 170/105 mmHg).
Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1.
Known active infection with hepatitis C, hepatitis B or HIV diagnosed by initial serological testing and confirmed with RNA testing, or prior treatment for hepatitis C. Testing for these infections is not included in the screening process; only prior knowledge of these infections, for example, in the patient's medical record, will be considered. Patients positive by serology, but negative by RNA may be deemed eligible by the Investigator in consultation with the MSM.
Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated. Patients with a history of other malignancies that have been treated with curative intent and which have no recurrence within 5 years may also be deemed eligible by the Investigator in consultation with the Medical Safety Monitor (MSM).
Participation in a different clinical trial of experimental (approved or investigational) therapy for prion disease within 4 months prior to Screening.
Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator.
Concomitant treatment with immune modulating therapy and/or diagnosis of a disorder that may require treatment with immune modulating therapy including, but not limited to, autoimmune disorders.
Previous treatment with an oligonucleotide (including siRNA) within 4 months of screening. (This does not apply to mRNA vaccines, including COVID-19 vaccines.)
History of bleeding diathesis or coagulopathy, or current or anticipated use of warfarin, apixaban or other anti-coagulant or anti-platelet medication that cannot be safely held for the appropriate time prior to LP.
Any contraindication to repeated LPs, including bleeding disorders, brain or spinal diseases or deformities. Examples include but are not limited to mass lesions, obstructive hydrocephalus, ventriculoperitoneal shunt, Chiari malformations, significant spondyloarthropathy and spinal stenosis, significant connective tissue disorders.
Any contraindication or unwillingness to undergo MRI, e.g., metal implants, claustrophobia, agitation, or motor symptoms that precludes scans) or MRI or CT results that suggest a different diagnosis or that trial participation would be unsafe.
Have any other condition, which, in the opinion of the Investigator would make the patient unsuitable for inclusion or could interfere with the patient participating in or completing the study.
Patients unwilling to comply with the contraceptive requirements during the study period.
Female patient is breastfeeding, pregnant or planning a pregnancy.