smb cafe 13 feb '14 - good biomarker sciences, future outlook
DESCRIPTION
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 http://www.sciencemeetsbusiness.nl/13-feb-2014/TRANSCRIPT
Proximal markers
Good Biomarker Sciences
www.gbsleiden.nl
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 CROguided 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
LipidFFA
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
NFkBearly
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
Aβ
eq
uiv
alen
ts (
fg/m
L)
Evaluation of CSF Samples: EP-AD
**
**
** 2,000
** p<0.001
1,500
1,000
500
0 Control MCI AD
N=62 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.
7
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.