Day 2 :
University of California, San Francisco, USA
Michael D Geschwind is a Professor of Neurology at the UCSF Memory and Aging Center who specializes in the assessment, treatment and management of rapidly progressive dementias, including prion diseases such as Jakob-Creutzfeldt disease (JCD) and autoimmune encephalopathies, and other cognitive/movement disorder syndromes. He helped to establish a program for the assessment of rapidly progressive dementias at UCSF Medical Center, the first of its kind in the country. He helped to run the first US treatment trial for sporadic disease, at UCSF. He has also helped to establish and co-direct a clinic for patients with autoimmune encephalopathy. He Co-directs the Huntington’s Disease Society of America Center of Excellence (HDSA COE) and Ataxia Clinic at the UCSF Memory and Aging Center. His research interests include rapidly progressive dementias, cognitive dysfunction in movement disorders, such as Huntington's disease, spinocerebellar ataxia, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and other Parkinsonian dementias.
Statement of the Problem: In my prior presentation I discussed the clinical spectrum of sporadic human prion disease, but these only account for 85% of human prion disease cases. About 15% of human prion diseases are genetic and about <1% are acquired. This talk will focus more on the genetic and acquired forms.
Methodology & Theoretical Orientation: Our center has evaluated more than 2500 cases of rapidly progressive dementia (RPD), including more than 600 cases of prion disease through our clinical research program. We have also been following about 100 families with genetic prion disease. Most patients undergo a comprehensive evaluation including clinical history, cognitive testing, CSF analysis, research brain MRI protocol and other testing. These data are analyzed to identify measures that might improve our understanding of these different forms of prion disease.
Findings: The clinical spectrum of acquired and genetic prion diseases is vast. For acquired prion disease, of most concern is the variant JCD from exposure to bovine spongiform encephalopathy and in the USA and some other countries there is concern than prion disease of deer, elk, and moose, chronic wasting disease, might spread to humans. These topics are discussed. For genetic prion disease, we have found the spectrum of presentation to be quite varied, from RPD to slowly progressive dementia and movement disorders over years to decades.
Conclusion & Significance: Acquired and genetic prion diseases have some overlap with, but also significant differences from, the more common sporadic disease. Improved understanding of the presentation of these disorders should allow earlier and more accurate diagnosis of these rare conditions.
National Taiwan University Science & Technology, Taiwan
Chris Whiteley is an Emeritus Professor of Biochemistry at Rhodes University, Grahamstown, South Africa and distinguished Research Professor at National
Taiwan University Science & Technology, Visiting International Professor in Enzymology at School of Bioscience & BioEngineering of South China University
Technology, Guangzhou, PRC. He served as Visiting Research Scientist at the Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan
in 2004 and as Visiting Professor of Biochemistry at Institute of Biomedical Technology, Veterans General Hospital, Yang Ming University, Taipei, Taiwan. He also
worked as Visiting Professor of Enzymology & Organic Synthesis at Oregon State University, Corvallis, Oregon, USA and Visiting Professor of Organic Synthesis
at University British Columbia, Vancouver, Canada. He is the Executive Member of Royal Chemical Society (London), MRSC (C. Chem), South African Chemical
Institute (SACI). He has published 6 chapters in books and has 110 peer-reviewed papers on Biomedical Enzymology and Nanomaterials.
Statement of the Problem: There is an increasing need for the development of new drug protocols against human immunedeficiency
virus (HIV) and HIV protease (HIVPR) is identified as a promising biomedical target in this regard.
Methodology: The interaction of gold nanoparticles (AuNP) with HIVPR is modelled using a molecular dynamics simulation
computer programme (Colores) from the Situs suite package.
Findings: The simulation of the ‘docking’, first as a rigid-body docked complex, and eventually through flexible-fit analysis,
creates 36 different complexes from four initial orientations of the nanoparticle strategically positioned around the surface of
the enzyme [Fig A]. The rigid-body docked complex is conformationally flexible to accommodate the AuNP that orientates
itself within the ‘docking’ site until a more stable structure is formed at convergence. Normalization of the data, for these
AuNP-HIVPR complexes, is obtained from changes to interactive binding energy profiles, RMSD, B-factors, dihedral angles
[phi, Δφ; psi, Δψ; chi, Δχ], size, volume occupied by Cα [ΔVcα], secondary structural elements (α-helix, β-strands, random
coil), number of contact residues, their hydrophobicities and surface electrostatic potentials.
Conclusion & Significance: From a molecular dynamic simulation perspective it is possible to provide insights into the ‘best’
most probable AuNP-HIVPR complex formed no matter which biophysical technique is monitored.
Stef Stienstra works internationally for several medical and biotech companies as Scientific Advisory Board Member and is also an active Reserve-Officer of the
Royal Dutch Navy in his rank as Commander (OF4). For the Dutch Armed Forces, he is CBRNe Specialist with focus on (micro) biological and chemical threats
and Medical- And Environmental Functional Specialist within the 1st CMI (Civil Military Interaction) Battalion of the Dutch Armed Forces. For Expertise France, he
is now managing an EU CBRN CoE public health project in West Africa. In his civilian position, he is at this moment developing with MT-Derm in Berlin (Germany)
a novel interdermal vaccination technology as well as a new therapy for cutaneous leishmaniasis for which he has won a Canadian Grand Challenge grant. With
Hemanua in Dublin (Ireland), he has developed an innovative blood separation unit, which is also suitable to produce convalescent plasma for Ebola virus disease
therapy. He has finished both his studies in Medicine and in Biochemistry in the Netherlands with a Doctorate and has extensive practical experience in cell biology,
immuno-haematology, infectious diseases, biodefense and transfusion medicine.
Sharing security threat information is a challenge for governments and their agencies. Especially in biotechnology and microbiology the agencies do not know how to classify or to disclose collected information on potential bio-threats. There is vague border between man-made and natural biological threats. An example is the several month delay of the publication of research on the transmissibility of H5N1 avian influenza virus in the leading scientific journal Science by researchers of the Erasmus Medical Centre in Rotterdam, The Netherlands. The publication was delayed in 2012 by several months due to the fact that various organizations first wanted to investigate whether the details could be misused by malicious individuals. In the study the researchers show that only a small number of mutations were necessary to change the H5N1 virus so that it can spread through the respiratory system between mammals. This implies that the risk of a H5N1 pandemic cannot be ruled out. On the other hand, this information can be used to develop new therapies and/or vaccines for influenza. It gives also insight into the disease mechanism, which helps in the prevention. The same arguments are valid for therapeutic antibodies, like the antibodies, which are developed to treat anthrax. They have an extreme high affinity for the lethal factors of the bacterium and stop the disease, but the same antibodies could be misused to select the most pathogenic strains. Micro-organisms have from nature itself the capacity to reorganise and change their pathogenicity, which could lead to a pandemic spread of a disease. But if the disease is too infectious and too deadly, like some stains of Ebola Virus are, the lethality will be locally limited. But if the incubation time is longer in a certain strain of an Ebola virus, the risks on epidemics and even a pandemic is much higher. The knowledge of these natural mutation mechanisms could be misused to weaponize micro-organisms. It enables the engineering of the lethality like it is done with some anthrax strains. Are these laboratory techniques considered as public science or should it be classified? Academics want to publish and to share information for the progress of science and to find useful applications. The Rotterdam scientists were really annoyed when their research was blocked for publication and feared that other groups would be first in publishing a part of their obtained experimental results. Biosafety is already common practice in micro-biology, but biosecurity is often still questionable. A ‘Code of Conduct’, like the Dutch Academy of Science has developed, would help; especially for the so-called insider risk. Educational programs for the identification and assessment of risks and threats to security have to be developed to give scientists bio-threat awareness and for government officials to rationalize the real threat, without damaging the progress of science.