Investigating new treatments for Creutzfeldt–Jakob disease

For many years, therapeutic interventions for patients with Creutzfeldt–Jakob disease (CJD) or other forms of human spongiform encephalopathy were beyond clinical consideration. In the 1980s and early 1990s, only individual case reports were available in the literature (figure); clinical trials and systematic clinical observations of patients with CJD did not begin until the mid-1990s. Trials and systematic observations have since examined agents such as flupirtine, quinacrine, doxycycline, and pentosane polysulfate. The first randomised study of a therapy for CJD investigated flupirtine, which showed no efficacy in terms of survival time but did potentially slow cognitive decline. 1 Otto M Cepek L Ratzka P et al. Efficacy of flupirtine on cognitive function in patients with CJD: a double-blind study. Neurology. 2004; 62: 714-718 Crossref PubMed Scopus (155) Google Scholar Further randomised trials followed that examined quinacrine and doxycycline. 2 Geschwind MD Kuo AL Wong KS et al. Quinacrine treatment trial for sporadic Creutz-feldt-Jakob disease. Neurology. 2013; 81: 2015-2023 Crossref PubMed Scopus (91) Google Scholar , 3 Haïk S Marcon G Mallet A et al. Doxycycline in Creutzfeldt-Jakob disease: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2014; 13: 150-158 Summary Full Text Full Text PDF PubMed Scopus (117) Google Scholar A study in a small number of patients with CJD provided weak evidence that doxycycline, when used early in the disease course, could slow the clinical course; 4 Varges D Manthey H Heinemann U et al. Doxycycline in early CJD: a double-blinded randomised phase II and observational study. J Neurol Neurosurg Psychiatry. 2017; 88: 119-125 Crossref PubMed Scopus (42) Google Scholar however, no effect was observed in a randomised trial. 3 Haïk S Marcon G Mallet A et al. Doxycycline in Creutzfeldt-Jakob disease: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2014; 13: 150-158 Summary Full Text Full Text PDF PubMed Scopus (117) Google Scholar In The Lancet Neurology, Simon Mead and colleagues 5 Mead S Khalili-Shirazi A Potter C et al. Prion protein monoclonal antibody (PRN100) therapy for Creutzfeldt–Jakob disease: evaluation of a first-in-human treatment programme. Lancet Neurol. 2022; 21: 342-354 Summary Full Text Full Text PDF Scopus (3) Google Scholar now report results from a different type of investigation, in which a monoclonal antibody to cellular prion protein was given to six patients with CJD as a treatment allowed under a Specials Licence. Prion protein monoclonal antibody (PRN100) therapy for Creutzfeldt–Jakob disease: evaluation of a first-in-human treatment programmeOur academic-led programme delivered what is, to our knowledge, the first rationally designed experimental treatment for human prion disease to a small number of patients with CJD. The treatment appeared to be safe and reached encouraging CSF and brain tissue concentrations. These findings justify the need for formal efficacy trials in patients with CJD at the earliest possible clinical stages and as prophylaxis in those at risk of prion disease due to PRNP mutations or prion exposure. Full-Text PDF