Human Prion Diseases

Professor Maurizio Pocchiari is a neurologist working at the Istituto Superiore di Sanità, Rome, Italy, where chairs the Department of Neuroscience. He heads a group of neurologists, geneticists, biochemists, and statisticians working on various aspects of human and experimental prion diseases. These include studies on clinical and molecular epidemiology, diagnosis, pathogenesis, experimental therapy, biochemistry and molecular and cellular biology of the prion protein and the prion protein gene, development of new techniques for the inactivation of prions, and the analysis of risk in transmitting prions from animal-to-human or from human-to-human. Professor Pocchiari runs the Italian Creutzfeldt-Jakob disease surveillance unit since 1993 and is a member of the Coordination Committee of the European Creutzfeldt-Jakob disease Surveillance Network (EuroCJD) of the European Centre for Disease Prevention and Control (ECDC). Prof. Manson is an internationally recognised leading scientist in TSE research and has developed, delivered and managed a high international scientific programme involving studies of animal and human Transmissible Spongiform Encephalopathies (TSEs). She develops and uses in vivo and in vitro model systems to define the basic mechanisms of disease and to address practical issues involving the TSEs. She heads a division of six group leaders and forty scientific staff all researching TSEs. She also runs a research group of seventeen people, including postdocs, technicians and PhD students. The transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases affecting humans and animals. TSEs present with characteristic pathology which can include neuronal loss, reactive astrogliosis, deposition of disease-associated prion protein (PrP) and vacuolation in the brain. The aim of her group is to examine the role of host PrP in TSEs such as scrapie, bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jakob disease (CJD), the nature of the infectious and neurotoxic agent and to define routes of transmission between and within animal Basic research into neurodegenerative processes has also led into study of other diseases such as Alzheimer’s disease. They use a variety of models from the molecular to whole animal level of study. They have produced a number of unique transgenic mouse models via gene-targeting and with these models we are investigating the effects of PrP sequence, the species barrier, the influence of PrP glycosylation on disease susceptibility and also the expression of PrP in various cell-types or at specific time-points during disease. The group also investigates human to human transmission of vCJD via blood transfusion and other potential routes. Their research programme currently receives funding from a number of different sources including BBSRC, MRC, DEFRA, DoH and EU.

1. Historical view

Section I: Pathophysiology of prions 2. The cellular and pathological prion protein 3. Cell biology of prion infection 4. Experimental models of human prion diseases and prion strains 5. The role of the immune system in prion infection

Section II: Animal prion diseases (clinical, epidemiology, neuropathological, biochemical, biomarker, and genotypes) 6. Typical and atypical scrapie 7. Typical and atypical BSE 8. Chronic Wasting Disease

Section III: Human prion diseases (clinical, epidemiology, neuropathological, biochemical, biomarker, and genotypes) 9. Sporadic Creutzfeldt-Jakob Disease 10. Variably protease-sensitive prionopathy 11. Variant Creutzfeldt-Jakob Disease 12. Iatrogenic Creutzfeldt-Jakob Disease 13. Genetic Creutzfeldt-Jakob Disease 14. Gerstmann-Sträussler-Scheinker disease 15. Sporadic and fatal Familial Insomnia

Section IV: Prion-like mechanisms in other neurodegenerative diseases 16. Prion-like mechanisms in Alzheimer 17. Prion-like mechanisms in Parkinson 18. Prion-like mechanisms in ALS

Section V: Diagnosis and treatment 19. Prion protein amplification techniques 20. Differential diagnosis with other rapid progressive dementias 21. Symptomatic treatment, care and support of CJD patients 22. Identifying therapeutic targets and treatment in model systems 23. Vaccination strategies 24. Clinical trials

Section VI: Public health issues 25. Animal diseases and the zoonotic potential 26. Safety of blood, blood derivatives and plasma-derived products 27. Safety in clinical practice 28. Concluding thoughts