University Hospitals Cleveland Medical Center has registered a new registry and natural history study, PROSPECT, to follow adults who carry or are at risk of mutations in the PRNP gene, the cause of genetic prion disease, according to the study's listing on ClinicalTrials.gov (NCT07732608), first posted July 29, 2026. The study is observational: it will not test a drug or device, but will collect genetic, cognitive, neuropsychiatric, symptom and survival data over an estimated decade, with an estimated start date of August 17, 2026 and an estimated primary completion in August 2036. The listing describes the goal as characterizing the onset and progression of genetic prion disease in mutation carriers, information intended to support future biomarker development and prevention trials. The study is sponsored by University Hospitals Cleveland Medical Center, with Case Western Reserve University, the CJD Foundation and the Prion Alliance listed as collaborators, and Dr. Brian Appleby, a physician at University Hospitals, named as the responsible investigator. As of its most recent status update, the study had not yet begun recruiting.
The registry sits alongside, but is distinct from, two other kinds of prion disease infrastructure already running at the same institutions. Case Western Reserve University is home to the National Prion Disease Pathology Surveillance Center, which UH has described as tracking diagnosed prion cases largely through pathology confirmation, often after death. Separately, UH was the first site activated, in December 2024, in an international trial of an antisense oligonucleotide drug from Ionis Pharmaceuticals aimed at lowering prion protein levels in patients, according to a UH account of that trial. PROSPECT differs from both: it enrolls people before they show symptoms, to build a longitudinal picture of the presymptomatic and early phase of disease that neither a postmortem surveillance registry nor a treatment trial is designed to capture.
The idea of following at-risk PRNP carriers over time is not new. A biomarker study called OBSERVE, based at Massachusetts General Hospital and open since 2017, enrolls adults who are known PRNP mutation carriers or first-degree relatives of people with prion disease, according to its ClinicalTrials.gov listing. Researchers in Israel have also published a protocol, in BMC Neurology in 2023, for a natural history study of carriers of the E200K PRNP mutation, describing that country's cluster of familial Creutzfeldt-Jakob disease as home to the world's largest known population of people at genetic risk. What is new about PROSPECT is its scale of ambition, a full decade of planned follow-up, its academic-advocacy partnership structure involving two patient organizations, and its explicit framing as groundwork for prevention trials rather than a stand-alone scientific project.