7 steps How to prevent Thalassemia : Dr Sharda Jain & Vandana Gupta
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Cadth 2015 c5 1. cashman rare diseases
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. 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
(Aฮฒ Oligomer Epitope)
Prothena Biosciences
(Scientific Advisory Board)
Industrial Engagement
4. Disruptive Idea 2: Antibodies Can Selectively Target
Misfolded Proteins while Sparing Native Isoforms
Efficacy: Specific targeting
of a pathogenic species
โ Neutralization of toxicity
โ Blockade of propagation
โ Acceleration of degradation
โ Minimal โtarget distractionโ
Safety: Selective sparing of
normal proteins
โ Preservation of normal function
โ Minimization of autoimmunity
โ Minimal regimens in
therapeutic vaccines
5. 5
Amorfix Aggregated Aฮฒ Assay (A4):
Test Overview
Part 1: Aฮฒ Aggregate Isolation Part 2: Aฮฒ Quantification
Disaggregated Aฮฒ
Magnetic
bead coupled
to 1F8/2H12
Europium
bead coupled
to 4G10
Aฮฒ Ultra-Sensitive Immunoassay
AMFIAโข Quantifies Aฮฒ in its monomeric form
Immunoassay sensitivity
Aฮฒ-Disaggregation
ELUATE
(aggregated Aฮฒ)
FLOW
(monomeric Aฮฒ)
A4 Matrix
Capture and concentrate
Aฮฒ 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
A๏ข42
A๏ข40
28 fg 1.8 pg
assay bkgd
A๏ข (pg/well)
RFU
6. Propagated Protein Misfolding Diseases
ALS
(aggregates)
Parkinsonโs diseases
(Lewy Bodies)
Alzheimerโs diseases
(plaques and tangles)
Prion diseases
(PrP amyloid plaques)
Huntingtonโs disease
(aggregates)
TTR amyloid
neuropathy
(plaques)
Schizophrenia
(aggregates)
Type 2 diabetes
(aggregates)
7. Acknowledgements
University of Toronto
Chakrabartty group
Pai group
Prosser group
U Sask โ 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
Editor's Notes
Structured to unstructured, unstructured to structured
Safety: Selective sparing of normal proteins
Minimization of autoimmunity (TGN1412, A beta, etc.)
Minimal regimens in herapeutic vaccines
The โuniverseโ of propagating protein misfolding diseases.