Conference On Prion Diseases Turin, Italy, 3-6 October 2006

[flatfish]

Subject: CONFERENCE ON PRION DISEASES OF NEUROPRION, NETWORK OF EXCELLENCE, TURIN, ITALY, 3-6 OCTOBER 2006
Date: February 15, 2007 at 11:37 am PST
Prion2006 Abstracts

Welcome Address

Dear colleagues:

on behalf of the European Network of Excellence NeuroPrion and the Italian prion

researchers, we are happy to welcome you in Torino to the international conference “Prion

2006: strategies, advances and trends towards protection of society”.

The aims of the European Network of TSE researchers are to integrate and coordinate the

research efforts of their members in prevention, treatment, control and management of prion

diseases and to avoid future crises related to prions.

On the heels of Paris 2004 and Düsseldorf 2005, Prion 2006 is a further step in the better coordination

and reinforcement of international research activities.

It was your contribution that enabled us to put together a programme of exceptional scientific

excellence which will be equally attractive in the different areas of prion research. The

scientific programme of “Prion 2006” includes 5 plenary lectures, more than 50 oral

presentations selected from almost 400 abstracts, and poster sessions on the classical

themes of the NeuroPrion network (i.e., prevention, control, treatment, management and risk

analysis of prion diseases). This event provides a great opportunity for scientists from all

over the world to share their thoughts, findings and progress in this attractive and interesting

setting.

The meeting is also an opportunity to know one of the nicer town in Italy. Torino was the first

Italian capital and a lot of beautiful memories passed on through buildings, royal residences

and gardens in the heart of the city. Torino is a treasure of historic cafes, located throughout

the twelve kilometers of arcades that wind through the center’s streets and squares.

We would like to thank the Italian Ministry of Health, the Regione Piemonte, the City of

Torino, the CRT Foundation, the European Commission and a number of industrial sponsors

for their generous funding of this great event.

We wish you all a pleasurable and inspiring time in Torino!

Maria Caramelli, Torino

Gianluigi Forloni and Fabrizio Tagliavini, Milano

Jean-Phillippe Deslys and Jens Schell, Paris



Content

WELCOME ADDRESS 1

ORAL PRESENTATIONS 21

POSTER SESSION

Epidemiology 51

Risk Assessment 65

Genetics 74

Structural Determinants of Infectivity and Strains 90

Prion Strains in Humans and Animals 106

Pathogenesis 126

Cell Biology of PrPC and PrPSc 158

Diagnosis 186

Therapy 218

Prion Safety 231

WORKSHOP OF THE NEUROPRION CERVID GROUP 240

Final program 241

Abstracts 243


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ORAL-05

EPIDEMIOLOGY OF HUMAN TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

M. Pocchiari, M. Puopolo, for the EUROCJD surveillance

Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit*, Rome, Italy; pocchia@iss.it

An international study of the epidemiologic characteristics of human transmissible spongiform

encephalopathy (TSE) diseases was established in 1993 and included national registries in France,

Germany, Italy, the Netherlands, Slovakia, and the United Kingdom. In 1997, the study was extended

to Australia, Austria, Canada, Spain, and Switzerland. Data were pooled from all participating

countries for the years 1993 to 2004 and included deaths from definite or probable TSE diseases of

all etiologic subtypes. Five thousand six hundred fifteen cases were available for analysis and

included 4,727 cases of sporadic Creutzfeldt-Jakob disease (CJD), 560 genetic cases, 170 iatrogenic

cases, and 158 variant cases. The overall annual mortality rate between 1999 and 2004 was 1.68 per

million for all cases and 1.42 per million for sporadic CJD. There was heterogeneity in the distribution

of TSE cases by etiologic subtype.

Data for the analyses of predictors of survival were available in sporadic (n = 4618), iatrogenic (n =

163) and variant Creutzfeldt–Jakob disease (n = 158), and in cases associated with mutations of the

prion protein gene (n=530). Overall, survival for each disease type was assessed by the Kaplan–

Meier method and the multivariate analyses by the Cox proportional hazards model.


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ORAL-07

RISK LINKED TO BLOOD

M L Turner, Scottish National Blood Transfusion Service

Although Blood Services have taken a precautionary approach over the past 10 years in relation to

the possibility that variant CVD may be transmissible by blood and tissues, emerging evidence that

there may be a significant cohort of individuals with sub-clinical disease, along with three cases of

transmission of variant CJD prions by blood components, has increased concern that blood

transfusion and tissue transplantation may provide a route to extension of the outbreak of this

disease. The exact level of risk remains difficult to assess because of continuing uncertainties

around the prevalence of sub-clinical disease, the concentration and distribution of infectivity and the

overall transmissibility of variant CJD by these routes. Similarly, the extent to which current risk

reduction measures including donor selection and universal leucodepletion are effective in reducing

the risk of transmission is unclear. Newer technologies including prion reduction filters and peripheral

blood prion assays may provide a significant improvement in management of this risk, but there are

problems in terms of validation, countervailing risks and ethical and social considerations.


CONTINUED

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ORAL-09

THE OIE SYSTEM FOR THE EVALUATION OF COUNTRY STATUS FOR BOVINE SPONGIFORM

ENCEPHALOPATHY

Elisabeth Erlacher-Vindel and Gideon Brückner; World Organisation for Animal Health (OIE), 12 rue de Prony,

75017, Paris, France

The Terrestrial Animal Health Code of the World Organisation for Animal Health (OIE) (Chapter

2.3.13) makes provision for the BSE risk status of the cattle population in a country, zone or

compartment to be determined on the basis of a risk assessment and other evaluation criteria

described in the Terrestrial Code. Pending the outcome of the risk assessment the cattle population

in a country, zone or compartment can be classified as a negligible BSE risk, a controlled BSE risk or

an undetermined BSE risk. Applications of Member Countries are assessed using the information in

the completed questionnaire for BSE status recognition, the requirements of Chapter 2.3.13 and the

guideline for Surveillance for BSE (Appendix 3.8.4) of the Terrestrial Code. The applications of

Member Countries are evaluated by an ad hoc Group of experts and recommendations made to the

OIE Scientific Commission for Animal Diseases. Every year, during the General Session in May, the

International Committee of the OIE composed of the Official delegates of the OIE Member Countries

adopts a list by Resolution of countries recognised as a negligible BSE risk or a controlled BSE risk

The adoption of Resolution XXVII at the 74th General Session of the OIE in May 2006, giving

recognition by the International Committee of the OIE to the bovine spongiform encephalopathy

(BSE) categorisation status of several Member Countries, also signifies the acceptance by the

European Commission, the EU Council and the EU Parliament of a process that would now be the

sole responsibility and mandate of the OIE replacing the evaluation and classification process for the

allocation of a GBR index in respect of BSE to Member States and third countries by the European

Commission.

The Member Countries of the OIE that were listed following the adoption of Resolution XXVII, were

evaluated in accordance with the 2004 edition of the Terrestrial Animal Health Code with the

provision that any re-evaluations or new applications from Member Countries, will be done in

accordance with the 2006 edition of the Terrestrial Code or the Terrestrial Code current at the date of

evaluation and also using the questionnaire for BSE risk assessment that was adopted at the 74th

General Session. In the Resolution four countries were listed as BSE free and four countries as

provisionally free from BSE in accordance with the 2004 Terrestrial Code classification. The status

allocated to these countries will be published by the OIE until May 2008.


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ORAL-11

BIOLOGICAL PROPERTIES OF THE PRION STRAIN LINKED TO THE AMYLOIDOTIC FORM OF

BOVINE SPONGIFORM ENCEPHALOPATHY (BASE)

F. Tagliavini1, R. Capobianco1, C. Casalone2, S. Suardi1, M. Mangieri1, C. Miccolo1, L. Limido1, M. Catania1,

G. Rossi1, G. Giaccone1, C. Corona2, D. Gelmetti3, G. Lombardi3, M.H. Groschup4, A. Buschmann4, G.

Zanusso5, S. Monaco5, M. Caramelli2

1Istituto Nazionale Neurologico Carlo Besta, Milan, Italy, 2Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle

d'Aosta, Torino, Italy, 3Istituto Zooprofilattico Sperimentale della Lombardia ed Emilia Romagna, Brescia, Italy, 4Friedrich-

Loeffler-Institut, Greifswald-Insel Riems, Germany, 5Department of Neurological and Visual Science, University of Verona, Italy

In the past few years, two atypical forms of bovine spongiform encephalopathy (BSE) have been

recognized in different European countries, Japan and USA through active surveillance systems. One

of these phenotypes has been identified in Italy and is distinguishable from classical BSE for

remarkable differences in pattern of deposition and brain regional distribution of PrPSc, with presence

of PrP-immunoreactive amyloid plaques and severe involvement of the olfactory system with relative

sparing of the brainstem. The molecular signature of this “amyloidotic” form of bovine spongiform

encephalopathy, named BASE, is a PrPSc type having a protease-resistant core of lower molecular

mass than BSE-PrPSc with predominance of the monog*****ylated species. We carried out strain

typing studies using transgenic mice expressing bovine PrP (Tg Bov mice) and inbred lines of nontransgenic

mice, including SJL, C57Bl/6, RIII and VM mice. Both BSE and BASE transmitted readily

to Tg Bov mice, and produced different clinical, neuropathological and molecular disease phenotypes

indicating the propagation of two distinct prion strains. Conversely, all inbred mouse lines showed a

substantial barrier to primary transmission of BASE. Unexpectedly, second-passage transmission of

the BASE strain to non-transgenic mice induced a neuropathological and molecular disease

phenotype indistinguishable from that of BSE-infected mice. The existence of more than one agent

associated with prion disease in cattle and the ability of the BASE strain to convert into the BSE strain

may have important implications with respect to the origin of BSE and spongiform encephalopathies

in other species including humans.


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ORAL-24

STRAIN VARIABILITY IN BOVINE ATYPICAL TSES

T. Baron1, A.G. Biacabe1, A. Bencsik1, J. Jacobs2, J.P.M. Langeveld2, P.L. Acutis3, M. Polak4, D. Gavier-

Wid*n5, A. Buschmann6, M.H. Groschup6, J. A. Richt7

1 AFSSA, Lyon, France t.baron@lyon.afssa.fr; 2 CIDC-Lelystad, Dept. Bacteriology & TSEs, Lelystad, The

Netherlands, 3 CEA – Istituto Zooprofilattico del Piemonte, Turin, Italy, Turino, Italy; 4 NVRI, Dept. Virology,

Pulawy, Poland; 5 SVA, Upssala, Sweden; 6FLI-INEID, Riems, Greifswald, Germany; 7 NADC/USDA, Ames,

Iowa, U.S.A.

Since 2003, some cases of prion diseases in cattle have shown unusual features as assessed by

molecular characterization of the protease-resistant prion protein (PrPres) and/or histopathology,

when compared to the unique features of BSE described previously. Similar cases have now been

recognized in a number of countries, and an overview of the current situation will be presented. Such

studies have allowed to refine the molecular definition of such cases using Western blotting, referred

as H-type (Biacabe et al., 2004) or L-type (BASE)(Casalone et al., 2004). While a single strain of

infectious agent had previously been recognized when BSE was transmitted to a panel of genetically

defined inbred wild-type mice, the recent unusual findings raised the question of transmission of prion

disease from such unusual isolates. We could show transmission of prion disease from unusual BSE

isolates in murine experimental models (including wild-type and transgenic mouse lines). Most

importantly, data obtained during the characterization of experimentally infected mice showed

different features when compared to those previously described in mice infected with typical BSE

isolates. The unusual PrPres molecular features initially described in the brain of cattle by Western

blot were maintained following transmission of the agent into mice. In this presentation, the potential

origin of such cases, including the possible existence of “sporadic” forms of prion diseases in cattle,

will be discussed.



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