First-in-Human Trial of Anti-PrP Monoclonal Antibody PRN100 in Creutzfeldt-Jakob Disease: A Preliminary Evaluation

Human prion diseases like Creutzfeldt-Jakob disease (CJD) are severe and fatal, without treatment options. The process of these diseases involves the transformation of normal cellular prion protein (PrP^C) into harmful prions. A new approach targeting PrP^C has been tested in preclinical studies. A clinical trial was conducted to test an anti-PrP^C monoclonal antibody (PRN100) in six probable CJD patients at a hospital in London.

The treatment involved PRN100, a humanized antibody, administered intravenously every two weeks, starting with a titration phase and followed by doses of 80-120 mg/kg. The patients were monitored for side effects and disease progression was evaluated using specific scales. Additionally, autopsies were performed on two patients for further analysis.

The study found that PRN100 was well-tolerated and achieved the desired drug concentration in the cerebrospinal fluid (CSF) of four patients. No major adverse reactions were observed, but all patients showed neurological decline. The autopsied patients showed no cytotoxicity and some differences in prion protein patterns, suggesting the drug's effect. The drug was found in various concentrations in the brain tissue of one patient.

The study concludes that PRN100 represents a novel treatment for prion diseases and was safe with promising drug levels in the CSF and brain tissue. This supports the need for further trials in early-stage CJD patients and as a preventative measure for those at genetic or exposure risk.

The study was funded by several organizations, including the Cure CJD Campaign, the National Institute for Health Research UCLH Biomedical Research Centre, the Jon Moulton Charitable Trust, and the UK MRC.