2022 Virtual Conference - PRN100 therapy for CJD: evaluation of a first-in-human treatment programme

Presented By: Prof John Collinge, Professor of Neurology, MRC Prion Unit at UCL, UCL Institute of Prion Diseases
John Collinge is Professor of Neurology and Head of the Department of Neurodegenerative Disease at the UCL Institute of Neurology, and Director of the MRC Prion Unit. He also directs the NHS National Prion Clinic at the adjacent National Hospital for Neurology and Neurosurgery. Professor Collinge trained in medicine at the University of Bristol and in neurology at St Mary’s Hospital and the National Hospital for Neurology and Neurosurgery in London. He is committed to highly multidisciplinary research and the seamless integration of basic laboratory and clinical research. He established the MRC Prion Unit at Imperial College in 1998 where he held the positions of Wellcome Senior Clinical Fellow and then Wellcome Principal Clinical Fellow. His laboratory demonstrated in 1996 that the new human prion disease, variant CJD, was caused by the same prion strain as that causing BSE in cattle and has been responsible for a number of key advances in the field. Professor Collinge has served on numerous Government advisory committees on prion disease at a national, European Union and international level. He is committed to public communication of the Unit’s research and gives many media interviews. He is a Founder Fellow of the Academy of Medical Sciences, a Fellow of the Royal Society and was awarded a CBE for services to medical research.
Study Background:
Human prion diseases, including Creutzfeldt-Jakob disease (CJD), are rapidly progressive, invariably fatal neurodegenerative conditions with no effective therapies. Their pathogenesis involves the obligate recruitment of cellular prion protein (PrPC) into self-propagating multimeric assemblies or prions. Preclinical studies have firmly validated the targeting of PrPC as a therapeutic strategy. We aimed to evaluate a first-in-human treatment programme using an anti-PrPC monoclonal antibody under a Specials Licence.
Interpretation:
Our 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.