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From: TSS ()
Subject: 10th Anniversary of CHI's Transmissible Spongiform Encephalopathies Conference
Date: February 22, 2006 at 7:17 am PST

10th Anniversary of CHI's Transmissible Spongiform Encephalopathies Conference



Spongiform Encephalopathy meetings, we bring together for the first time all of the laboratories developing diagnostic blood tests for a head-to-head comparison of their methodologies and achievements. Other important topics include an expanded discussion about protein misfolding, reviews of BSE, vCJD, and CWD, updated tissue infectivity data, new methods of decontamination in hospitals and industry, filter technology for removing infectivity from blood, strategies being explored for therapeutic intervention, and a concluding panel on issues of FDA and USDA regulation.

Scientific Advisors
Dr. Paul Brown
Dr. Larisa Cervenakova, The American Red Cross
Dr. Kiki Hellman, Hellman Associates LLC












For more information, please contact, fax or e-mail submissions to:
Elizabeth Lamb, Conference Producer, Cambridge Healthtech Institute
Fax: 207-493-4573 • E-mail:

For exhibits and sponsorship information, please contact:
Suzanne Carroll, Manager, Business Development
Phone: 617-630-1352 • E-mail:

Day 1


On this 10th Anniversary of the CHI Transmissible Spongiform Encephalopathies meetings, we bring together for the first time all of the laboratories developing diagnostic blood tests for a head-to-head comparison of their methodologies and achievements. Other important topics include an expanded discussion about protein misfolding, reviews of BSE, vCJD, and CWD, updated tissue infectivity data, new methods of decontamination in hospitals and industry, filter technology for removing infectivity from blood, strategies being explored for therapeutic intervention, and a concluding panel on issues of FDA and USDA regulation.

Scientific Advisors
Dr. Paul Brown
Dr. Larisa Cervenakova, The American Red Cross
Dr. Kiki Hellman, Hellman Associates LLC

Tuesday, March 7

12:30 Registration

Joint Session with Blood Product Safety
A Forum on TSE Diagnostic Blood Tests

1:20 Comments by Session Chairperson
Dr. Paul Brown

1:30 Detection of PrPsc in Blood using Newly Developed Multimer Detection System
Dr. Seong An, Research Fellow, Research & Development, PeopleBio Inc.
Transmissible spongiform encephalopathies(TSEs), also known as prion (PrP) diseases, can spread not only through the food supply, but through organ transplants, contaminated medical instruments, the blood supply, or pharmaceuticals made from animal products. Recently, two patients died of variant Creutzfeldt-Jacob disease (CJD) from probable blood transmission from an asymptomatic infected individual. We focused on the detection of the infectious form of prion (PrPsc) in blood. Thus, we have developed a new concept, called Multimer Detection System (MDS), using one epitope-specific antibody system to differentiate the infectious PrPsc (multimer) from cellular PrP (monomer). MDS detected the PrPsc in various infectious samples - brain homogenate, plasma spiked with PrPsc and plasma from a diseased hamster.

1:50 Towards Development of a Prion Blood Test
Dr. David Peretz, Senior Scientist, Blood Testing R&D, Chiron Corporation
We have developed proprietary prion related peptide reagents that bind the pathogenic prion protein isoform, PrPSc. When coated on magnetic beads, the reagents effectively capture and concentrate human and sheep PrPSc from brain homogenates spiked in negative plasma samples. Combined with an ultra-sensitive ELISA this assay allows PrPSc to be detected at a level of a million-fold dilution of human CJD and sheep scrapie brain homogenate. Circulating scrapie prion has been detected in some plasma samples from infected sheep. The assay does not require Proteinase K digestion or centrifugation steps, and is therefore easily automated. In conclusion, feasibility of a prion assay format has been demonstrated with the potential to achieve the sensitivity and throughput required for screening human blood and animal blood samples.

2:10 Highly Sensitive Assay Detection for PrP in Hamster Plasma
Dr. Luisa Gregori, Molecular Neurovirology Lab, BREF
The risk of iatrogenic transmission of TSE infections could be effectively managed and controlled with a sensitive and reliable blood-based diagnostic assay. The assay should be capable of concentrating, discriminating and detecting trace amounts of PrPres from blood of pre-clinical individuals. We developed an assay platform that could form the basis for a TSE diagnostic assay for human plasma. This PrP-based assay was developed using normal hamster plasma and it combines the specificity of an antibody capture method and the sensitivity of the ORIGEN analyzer system. We improved the assay sensitivity by exploiting key features of the ORIGEN analyzer technology. Using recombinant hamster PrP as the standard, we measured the concentration of PrP in normal hamster plasma and in infected and normal hamster brains. We also assessed the assay sensitivity with brain-derived PrPres mixed in PrP-depleted hamster plasma. The results of these studies are reported and discussed in the context of assay requirements for a blood-based TSE diagnostics.

2:30 Detection of Prion Protein in Blood Samples
Dr. Maureen Dyer, Biological and Chemical Sensor Engineer, Hanson Technologies, Inc.
Presence of the prion protein is currently determined post-mortem. A blood test would allow for early detection, possibly even before clinical symptoms develop. Using technology licensed from the government, we are developing a rapid, automated, fluorescence-based sandwich assay screen for prion protein in blood. Infectious prion can be discriminated from the normal form through use of conformation specific antibodies.

2:50 Afternoon Refreshment Break, Poster Exhibit Viewing

3:40 The Misfolded Protein Diagnostic (MPD) Blood Assay: Current Status
Dr. Cindy Orser, Adlyfe, Inc. Rockville
Adlyfe has demonstrated the detection of misfolded prions in the blood of animals and humans using a novel blood based diagnostic called the Misfolded Protein Diagnostic (MPD) assay. Conformationally-dependent, labeled peptides that mimic the folding reaction of PrPC converting to PrPSC provide the basis for a blood-based diagnostic assay for PrPSC. Superior sensitivity is achieved due to signal amplification as additional labeled peptides are recruited in solution to undergo a similar conformation change. This has enabled the detection of PrPSC in blood of animals and humans infected with prion disease. The demonstration of the MPD Assay as a screening tool for the human blood supply is currently underway.

4:00 An Animal Model Evaluation and Assay Protocol for Screening Blood for vCJD
Dr. Stuart Wilson, Microsens Biotechnologies
Our Seprion ligand technology is specific for the abnormal form of the prion protein and does not bind the normal prion. The ligand has been built into an EU and USDA approved BSE test. We have developed the ligand further into a blood screening test and would like to present our latest protocol and latest data on evaluation of the test on the scrapie animal model.

4:20 Immunoassay for the Detection of Resistant Prion Protein (PrPres) in Human Plasma using an Original Combination of Chemical Ligands
Dr. Hervé Perron, Research Director, Senior Director Neurological Diseases Unit, R&D Immunoassay and Proteomics Department, bioMérieux
Detection of PrPres in human blood has been made possible by using the properties of two original ligands, Streptomycine and Claix-Arenes, with final specific antigenic detection using an anti-PrP monoclonal . Beyond the proof of principle of PrPres detection in human blood, detection in asymptomatic carriers and a test for excluding blood donations from such apparently healthy donors are the objectives of our R&D effort. Further studies and technical improvements are nonetheless required before a test prototype may be proposed for validation as a routine test for blood banking and/or human CJD diagnosis.

4:40 Rapid Blood Screening Test for CJD
Dr. Alex J. Raeber, Director of Research, Prionics AG
Two recent cases of vCJD in the UK caused by blood transfusion underscore the importance of implementing diagnostic blood tests for vCJD prions. We have developed rapid blood screening tests in two different assay formats, ELISA and fluorescence activated cell sorting (FACS) based on a capture and enrichment of PrPTSE from serum or plasma using the prion-specific antibody 15B3 and a subsequent detection step with a secondary
anti-PrP-specific antibody. Results from screening panels of TSE positive and negative sera will be presented and discussed.

5:00 Detection of Prions in Blood
Prof. Joaquin Castilla, Assistant Professor of Neurology, Protein Misfolding Disorders Lab, University of Texas Medical Branch, University of Texas, Galveston
Prion diseases are caused by an unconventional infectious agent termed prion, composed mainly of the misfolded prion protein (PrP(Sc)). The development of highly sensitive assays for biochemical detection of PrP(Sc) in blood is a top priority for minimizing the spread of the disease. Here we show that the protein misfolding cyclic amplification (PMCA) technology can be automated and optimized for high-efficiency amplification of PrP(Sc). We show that 140 PMCA cycles leads to a 6,600-fold increase in sensitivity over standard detection methods. Two successive rounds of PMCA cycles resulted in a 10 million-fold increase in sensitivity and a capability to detect as little as 8,000 equivalent molecules of PrP(Sc). Notably, serial PMCA enables detection of PrP(Sc) in blood samples of scrapie-afflicted hamsters with 89% sensitivity and 100% specificity. These findings represent the first time that PrP(Sc) has been detected biochemically in blood, offering promise for developing a noninvasive method for early diagnosis of prion diseases.

5:20 Question and Answer Period with all Session Speakers

5:45-6:45 Networking Reception in Exhibit Hall

Day 2


Wednesday, March 8

7:30 Morning Coffee, Poster and Exhibit Viewing


8:00 Comments by Session Chairperson
Dr. Paul Brown

8:05 Amyloid Diseases and Transmission: A Case for Conformational Genomics and Implications for Therapeutics
Dr. David Lynn, Chemistry & Biology, Emory University
We will discuss the peptide conformation assemblies found in two very different amyloid morphologies. A very subtle difference in the arrangement of the peptides in this case results in huge changes in morphology, morphologies that can be altered by minor changes in assemble conditions, the presence of metal ions and even with small molecues. These changes can now be used to modulate amyloid morphology, opening the possibility of regulating amyloid toxicity therapeutically.

8:35 Amyloid, Prions and the Inherent Infectious Nature of Misfolded Protein Aggregates
Prof. Claudio Soto, University of Texas, Galveston
Misfolded aggregates and amyloid fibrils are associated with a variety of diseases known as protein misfolding disorders. Among them, prion diseases are unique in that the pathology can be transmitted by an infectious process involving an unprecedented agent known as prion. The molecular mechanism of prion conversion has striking resemblance to the process of amyloid formation, suggesting that misfolded aggregates have an inherent capability to be transmissible. In addition, Amyloid and Prions, once thought to be exclusively associated with nasty diseases, have been recently found involved in the physiological function of diverse proteins. Recent understanding of the structural requirements for protein misfolding and aggregation suggest that most proteins have the potential to behave as prions. The possibility that many proteins adopt multiple conformations to exert different functions, and that this biological information can be propagated between cells and individuals might revolutionize our understanding of biology.

9:05 Synthetic Mammalian Prions: Hierarchical Assembly and Substructure of Amyloid Fibrils
Prof. Ilia Baskakov, Assistant Professor, Medical Biotechnology Center, University of Maryland Biotechnology
Misfolding and polymerization of prion protein underlie a group of fatal neurodegenerative maladies (transmissible spongiform encephalopathies) that can be infectious, inherited or sporadic in origin. Our understanding of the etiology and molecular mechanism of prion diseases has been advanced by creating the first synthetic mammalian prions. The current presentation summarizes our most recent studies on structural aspects of the in vitro conversion and generation of synthetic prions. New data on the mechanism of hierarchical assembly and substructure of fibrillar form of PrP will be discussed.

9:35 Relating Particle Size to Infectivity in Prion Protein Aggregates
Dr. Jay Silveira, Post Doctoral Fellow, NIAID Laboratory of Persistent Viral Diseases NIH Rocky Mountain Laboratories
TSE infectivity is associated with a wide range of prion protein aggregate sizes, but comparing particle size to infectivity has been difficult. A systematic evaluation of this relationship was accomplished by combining asymmetrical flow field-flow fractionation with in-line static and dynamic light scattering analyses, and revealed that with respect to PrP content, compact, subfibrillar particles are the most efficient initiators of TSE disease.

10:05 Coffee Break, Poster and Exhibit Viewing


10:35 Comments by Session Chairperson
Dr. Larisa Cervenakova, Transmissible Diseases Department, American Red Cross Holland Laboratory

10:40 Epidemiology Update on Animal TSE Diseases
Dr. Raymond Bradley, Private BSE Consultant
The talk will describe the current state of play of BSE and non-BSE related animal TSE, the major epidemiological features of BSE, the conditions for international trading in cattle-derived commodities, an analysis of BSE testing data from the EC, and proposals for reducing costs whilst maintaining protection of the European consumer as outlined in the EC TSE Roadmap.

11:10 CJD: Where are We with the Primary Outbreak and with Secondary Transmission?
Prof. Robert Will, CJD Surveillance Unit, Edinburgh
Cases of variant CJD have recently been identified in an increasing number of countries in Europe and also in Saudi Arabia and Japan. Exposure to BSE, the causal agent of vCJD, may be related to past travel to the UK, exposure to bovine exports from the UK or indigenous BSE. Some of the recent vCJD cases had been blood donors, underlining the importance of considering measures to minimize the risk of transfusion transmission of vCJD.

11:40 Chronic Wasting Disease Genetics and Diagnosis
Dr. Katherine O'Rourke, Research Microbiologist, USDA, ARS, ADRU
The endemic area of chronic wasting disease is slowly expanding. Molecular and genetic analysis of the prion gene and PrP-d from deer in different geographic areas may provide insight into strain variation in this emerging TSE. Rapid, high-throughput detection techniques should allow the wildlife regulatory agencies to perform more efficient surveillance as CWD is found in new areas.

12:10 Technology Short Talk (Sponsorship Available)

12:25 Lunch and Learn Workshop (Sponsorship Available)


1:25 Comments by Session Chairperson
Dr. Larisa Cervenakova

1:30 Tissue Infectivity/PrPBSE Distribution and Pathogenesis in Bovine Spongiform Encephalopathy (BSE)
Dr. Gerald A.H. Wells, Consultant Veterinary Pathologist, Veterinary Laboratories Agency
Infectivity and PrPBSE in tissues of cattle infected with the BSE agent has been studied in natural cases and experimentally induced disease. In contrast to scrapie of small ruminants, extra neural agent distribution appears restricted, involving some primary lymphoid tissue of the alimentary tract, without systematic spread throughout the lymphoreticular system. Pathogenetic involvement of neural tissues is consistent with experimental oral exposure models implicating autonomic nervous system pathways.

2:00 CJD: Current Status
Dr. James Ironside, CJD Surveillance Unit, Edinburgh

2:30 PrPres in Spontaneously Developing Lymphoreticular Tumors of Mice Infected with vCJD
Dr. Larisa Cervenakova
The lymphoreticular tissue of patients with variant CJD (vCJD) has been shown to accumulate protease-resistant prion protein (PrPres) and TSE infectivity. This observation led to retrospective and/or consecutive studies investigating presence of PrPres in archival lymphoreticular tissues, mainly appendices and tonsils, in the UK population to estimate the prevalence of preclinical and subclinical vCJD. We report that PrPres accumulates in spontaneous lymphoreticular tumors of vCJD-infected mice. This finding provides experimental evidence to support the idea that PrPres may accumulate in lymphoreticular system tumors of vCJD-infected individuals. Our study, together with a previous report on PrPres in inflammatory foci of experimental mice infected with scrapie, suggests that the statistical power of estimates of vCJD prevalence might be increased by expanding screening to include samples of lymphoreticular neoplasms and inflammatory tissues.

3:00 Afternoon Refreshment Break, Poster and Exhibit Viewing


3:30 Comments by Session Chairperson
Dr. Larisa Cervenakova

3:35 Disinfection in the Hospital and Laboratory: Newer, Gentler Methods
Dr. J-P Deslys, CEA, Paris

4:05 Removal of Endogenous TSE Infectivity from Blood by Affinity Ligands
Dr. Robert Rohwer, Molecular Neurovirology Lab, BREF
Removal of TSE infectivity from blood may be the most viable option to date to reduce the risk of human-to-human iatrogenic TSE transmission. Utilizing a combinatorial library of affinity ligands, Pathogen Removal and Diagnostic Technologies, Inc. (PRDT) evaluated millions of different chemical structures for binding to human, mouse and hamster PrPres. Selected lead compounds when immobilized on a solid resin support matrix demonstrated removal of 4-log10 of hamster brain-derived infectivity from human red blood cell concentrate. In a second study, lead ligands were tested for the removal of endogenous hamster blood TSE infectivity. Using the limiting dilution titration method, leucoreduced hamster whole blood was titered before and after the TSE infectivity removal device by inoculating 100 hamsters per sample and assessing animals for 540 days post inoculation. The final results will be presented and analyzed in the context of TSE infectivity removal requirements.

4:35 Improving the Safety of the Blood Supply - Filtration Technology for Removing Infectious Prions from Red Cell Concentrates for Transfusion
Dr. Samuel Coker, Principal Scientist and Technical Director, Pall Medical, Pall Corporation - Life Science
The recent occurrences of probable cases of transmission of vCJD through blood transfusion raises concerns about the safety of the blood supply and the possibility of transmission of the causative agent by blood transfusion from asymptomatic infected individuals. Since the first case of vCJD in 1995, one hundred and sixty four (164) people worldwide have died from the disease, which is believed to have emerged as a result of the consumption of meat from cattle infected with BSE. A new filtration technology that removes prions from red cell concentrates (RCC), the most widely transfused blood component, has been developed and is available commercially in Europe. The technical approaches used in developing this filtration technology, performance characteristics, along with the proposed mechanisms for removal of prions by the device are discussed in this article.

5:05 Conclusion of Day


Transmissible Spongiform Encephalopathies and Protein Folding Disorders
Joint Session

10th International
Transmissible Spongiform Encephalopathies
The Definitive American TSE Meeting
March 7-9, 2006 2nd International
Protein Folding Disorders
March 9-10, 2006

Thursday, March 9

8:30 Morning Coffee


9:00 Comments by Session Chairperson
Dr. Paul Brown

9:15 Vaccine Approaches to Prevent and Treat Prion Infection
Professor Thomas Wisniewski, Professor, Neurology, Pathology and Psychiatry, NYU School of Medicine
Immunological therapeutic approaches are currently being developed for a number of conformational neurodegenerative conditions, including Alzheimer's disease (AD) and prion disease. Passive immunization is now in clinical trial for the treatment of AD. We were the first to show in wild-type prion model mice that active and passive immunization can produce resistance to prion infection with prolongation of the incubation period. We are currently developing mucosal prion vaccines which can prevent infection in a proportion of animals later exposed to the prion agent orally. These studies can be used to develop active vaccines for livestock and eventually in humans who are at risk for developing prion infection.

9:45 Searching for Anti-TSE Compounds using Animal Models
Dr. David Kocisko, Staff Scientist, NIH/Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories
There is no treatment for the TSEs and they are always fatal. A number of potential TSE therapies were tested in transgenic mice and several new compounds have been found with in vivo prophylaxis activity. One of these new compounds also has activity when used as a treatment following scrapie inoculation into the brain, which places it in a small group of molecules with such activity.

10:15 Protein Origami: Molecular Folding in Health and Disease
Dr. P. Michael Conn, Associate Director and Senior Scientist, The Oregon National Primate Research Center; Special Assistant to the President and Professor of Physiology, Pharmacology, and Cell and Developmental Biology, Oregon Health and Science University
Mutants of the gonadotropin releasing hormone receptor are frequently misrouted within the cell, but otherwise competent proteins. "Pharmacoperones," small molecules that penetrate cells and correct folding, rescue such "defective" molecules, allowing the misfolded mutants to escape retention by the cell's quality control apparatus and route correctly to the plasma membrane. This observation and the indication that disease is a frequent corollary of protein misfolding/misrouting suggests that protein rescue may be an under-appreciated therapeutic approach. The observation that a percentage of wild-type proteins may also be misrouted suggests that this is a novel form of post-translational regulation associated with normal function that can also be therapeutically exploited.

10:45 Technology Short Talk (Sponsorship Available)

11:00 Coffee Break, Poster and Exhibit Viewing

SCIENCE AND POLICY: Joint FDA/USDA Panel on TSE-Safe Products: The Federal Role

11:30 Comments by Session Chairperson
Dr. Kiki Hellman, Hellman Associates LLC

11:35 Reducing TSE Risk for Biological Products: Regulatory Approaches
Dr. David M. Asher, Chief, Laboratory of Bacterial, Parasitic and Unconventional Agents, Division of Emerging and Transfusion-Transmitted Diseases, Office of Blood Research and Review, CBER, Food and Drug Administration

11:50 TSE Transmission by Surgical Instruments: Evaluation of Products Proposing to Reduce that Risk
Dr. Sheila A. Murphey, Branch Chief, Infection Control Devices Branch, Division of Anesthesiology, General Hospital, Infection Control and Dental Devices, Office of Device Evaluation, Center for Devices and Radiologic Health, Food and Drug Administration

12:05 Reducing TSE Risk for Biotechnology Products: Regulatory Approaches
Dr. Gerald Feldman, Senior Investigator, Laboratory of Molecular and Developmental Immunology, Division of Monoclonal Antibodies, Office of Biotechnology Products, OPS Center for Drug Evaluation and Research, Food and Drug Administration
Cytokines, monoclonal antibodies, and other biopharmaceuticals produced in cell culture have the potential of harboring TSE agents introduced through the use of animal-derived components at various stages in the production process. CDER's concern with, and approach to assuring the safety of these products will be discussed.

12:20 CVM Update on Feed Controls for Prevention of BSE
Dr. Burt Prichett, Division of Animal Feeds, Center for Veterinary Medicine, Food and Drug Administration

12:35 Title to be announced
Dr. Lisa Ferguson, Senior Staff Veterinarian, United States Department of Agriculture, APHIS, Veterinary Services

12:50 Lunch and Learn Workshop (Sponsorship Available)

Close of Transmissible Spongiform Encephalopathies


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