SmB cafe 13 feb '14 - Good Biomarker Sciences, future outlook

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Information about SmB cafe 13 feb '14 - Good Biomarker Sciences, future outlook

Published on March 13, 2014

Author: cmvangorkum



Presentation by Kees Kluft of Good Biomarker Sciences for the Science meets Business café of 13 Feb 2014. This event was held in the BioPartner 1 foyer in Leiden. For the report, see

Proximal markers Good Biomarker Sciences

Biomarker development laboratory. Haemostasis and inflammation models and biomarkers Immunogenicity / toxicity --- NEW: Disease markers Phase I-IIa unit Pharmacodynamic biomarkers Amyloid research

Our model • A research CRO guided by customer requests, and own idea’s new biomarkers models and platforms; be a partner in interpretation

ER ER ER UPR Inflammasome Cellular mechanisms

ER ER ER UPR Inflammasome high/low metabolic Lipid FFA Glucose virus PAMPS/DAMPSo.a. TLR4/LPS Specific triggers Homocysteine (B12) Alcohol Hypoxia Transfat Palmitate Uric acid Peroxynitrite glucosamine In the cell Mito Pro-apoptotic Anti-apoptotic Markers (CRP) Oxidation C/EBP-β (LPS, age) Cathepsin B/D Il-18 IL-1-beta Chaperone reduction NFkB early late Immunity pyroptosis Poluttants Asbestos Crystals amyloid

Not coping: Failure UPR • Debris in the cell – Cellular death • Activation inflammasome – Cellular death

After Hosoi, 2010 No balance anymore: debris

Final phase Inflammasome activation • Pyroptosis (inflammatory cell death) • Markers: Il-18, IL-1β (pain), Cathepsins • Auto-antibody increases

Aβequivalents(fg/mL) Evaluation of CSF Samples: EP-AD * * ** * * 2,000 ** p<0.001 1,500 1,000 500 0 Control MCI AD N = 6 2 N=50 N=79 Average signal 130.5 563.2 364.1 EP-AD detects aggregated Aβ in CSF of AD and MCI patients. All 3 groups are statistically significantly distinct. Overlap !

Late stage markers • Il-18, Il-1β, Cathepsins • Auto-antibody titers

Detection of auto-antibodies a) Many are present (low level) from birth on b) Disease specific patterns occur for multiple antigens per disease with an increase in titer and shift in type. c) Example HIV-infected people are “loaded” with auto-antibodies

Fattal. Immunol 130, 2010:337.

miRNA as disease markers

Signature of tissue state and disease

Exosomes and microparticles, HDL and carriers stabilise miRNA in biological fluids

Plasma contains MPs from different origin

Plasma contains MPs from different origin Tumor

New: MicroRNA-21 • Elevated in blood in cases with colorectal cancer • Established as diagnostic and prognostic biomarker Natl Cancer Inst 2013, 105:849-59. + Functionality • Inhibition improves sensitivity to chemotherapy.

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