cadth 2015 c5 1. cashman rare diseases

of 7/7
Neurodegenerative Diseases: The Distorted Origami of Protein Misfolding Neil R. Cashman MD Professor and Canada Research Chair Brain Research Centre Department of Medicine (Neurology) University of British Columbia Academic Director, ALS Centre GF Strong Hospital

Post on 07-Aug-2015

37 views

Category:

Health & Medicine

2 download

Embed Size (px)

TRANSCRIPT

  1. 1. Neurodegenerative Diseases: The Distorted Origami of Protein Misfolding Neil R. Cashman MD Professor and Canada Research Chair Brain Research Centre Department of Medicine (Neurology) University of British Columbia Academic Director, ALS Centre GF Strong Hospital
  2. 2. Caprion Pharmaceuticals Founder and Scientific Advisor (YYR PrPSc Epitope) Amorfix Life Sciences Founder and CSO, Chair BoD (Epitope Protection, SOD1 Epitopes, ProMIS) Biogen-Idec Corporation (SOD1 DSE Immunotherapy) Cangene Corporation (A Oligomer Epitope) Prothena Biosciences (Scientific Advisory Board) Industrial Engagement
  3. 3. Cancer Neurodegeneration Cancer Neurodegeneration Disruptive Idea 1: Protein Misfolding and Disease
  4. 4. Disruptive Idea 2: Antibodies Can Selectively Target Misfolded Proteins while Sparing Native Isoforms Efficacy: Specific targeting of a pathogenic species Neutralization of toxicity Blockade of propagation Acceleration of degradation Minimal target distraction Safety: Selective sparing of normal proteins Preservation of normal function Minimization of autoimmunity Minimal regimens in therapeutic vaccines
  5. 5. 5 Amorfix Aggregated A Assay (A4): Test Overview Part 1: A Aggregate Isolation Part 2: A Quantification Disaggregated A Magnetic bead coupled to 1F8/2H12 Europium bead coupled to 4G10 A Ultra-Sensitive Immunoassay AMFIA Quantifies A in its monomeric form Immunoassay sensitivity A-Disaggregation ELUATE (aggregated A) FLOW (monomeric A) A4 Matrix Capture and concentrate A aggregates INPUT Sample/homogenate preparationBrain, plasma, CSF, cell culture 0.01 0.1 1 10 100 1,000 2,000 4,000 8,000 16,000 32,000 64,000 128,000 256,000 512,000 A42 A40 28 fg 1.8 pg assay bkgd A (pg/well) RFU
  6. 6. Propagated Protein Misfolding Diseases ALS (aggregates) Parkinsons diseases (Lewy Bodies) Alzheimers diseases (plaques and tangles) Prion diseases (PrP amyloid plaques) Huntingtons disease (aggregates) TTR amyloid neuropathy (plaques) Schizophrenia (aggregates) Type 2 diabetes (aggregates)
  7. 7. Acknowledgements University of Toronto Chakrabartty group Pai group Prosser group U Sask VIDO, PREVENT Napper group CIHR: III, IA, INMHA ALS Canada PrioNet Canada Canada Research Chairs CFI & BCKDF Cangene/Emergent Corp UBC Cashman group Plotkin group Mackenzie group Jia group Marziali group Wang group Wellington group University of Alberta Wishart group Kovalenko group Amorfix Life Sciences