PRESS RELEASE
Novel Ultra Sensitive Protein Detection Technology Showcased at Alzheimer’s
Conference with identification of new biomarkers for early stage diagnosis and monitoring
of this disease.
Cobham, UK – 30th July, 2015. Proteome Sciences plc (‘Proteome Sciences’) gave three oral
presentations at last week’s Alzheimer’s Association International Conference, 2015 (AAIC),
highlighting how its proprietary TMTcalibrator™ and SysQuant® technologies are finding proteins
undetectable by other methodologies.
Two presentations focussed on how TMTcalibrator™ is enabling the detection and quantification of
very low abundant disease-related proteins in body fluids. TMTcalibrator™ provides two
advantages – direct evidence of fluid proteins at the site of the disease and higher sensitivity for
tissue leakage proteins that are the most powerful biomarkers. One of the most striking results was
the ability to detect and quantify over 40 phosphorylated peptides from tau protein in human CSF
using mass spectrometry, a feat that was impossible before the introduction of TMTcalibrator™.
The third presentation introduced the CrossQuant™ concept, where the true power of ‘Systems
Proteomics’ based on SysQuant® analysis to identify disease processes, followed by
TMTcalibrator™ to identify fluid biomarkers of each disease process was demonstrated in
Alzheimer’s disease. The SysQuant® experiments identified those cellular processes that change in
response to increasing tau toxicity in human disease but that were subsequently shown to be
reversed by reduction of toxicity in an experimental mouse model using Proteome’s proprietary
CK1d (casein kinase 1 delta) inhibitors. Having identified these pathways it was possible to generate
TMTcalibrator™ data to hunt for and discover key proteins responsive to tau toxicity in the brain
that can then be quantified in human CSF.
Proteome Sciences has patented the panel of biomarkers presented for use in the early diagnosis of
Alzheimer’s disease, predicting disease progression and monitoring the effectiveness of new
treatments, as new drug targets and as companion diagnostics.
Commending TMTcalibrator™ and SysQuant®, leading Alzheimer’s disease researcher, Professor
Henrik Zetterberg, MD, PhD of University of Gothenburg, an author on all three oral presentations
said:
“I am extremely impressed with the breadth of coverage and depth of protein
concentrations that can now be mined using the SysQuant® and TMTcalibrator™
technologies. The data sets generated are providing new insights into the disease processes
operating during the evolution of this devastating disease and most importantly enabling us
to find accessible fluid biomarkers which should allow us to detect Alzheimer’s disease
earlier and monitor the effectiveness of treatment. We are working together with Proteome
Sciences to extend replication of this most promising data in larger sample sets.”
Commenting on the utility of TMTcalibrator™ and SysQuant®, Dr Ian Pike, COO of Proteome
Sciences said:
“The combination of SysQuant® and TMTcalibrator™ presented at AAIC is a unique protein
detection platform that can be used from the earliest stages of diagnostic and drug
development through to clinical trials to provide unmatched levels of sensitivity.
“Our oral presentations at AAIC clearly demonstrate the ability of TMTcalibrator™ to
identify very low abundant proteins in complex body fluids with minimum fractionation
highlighting new biomarkers which could act as highly effective diagnostic and
pharmacodynamic biomarkers. The power and data density of SysQuant® and
TMTcalibrator™ is offering the opportunity to significantly reduce the cost and timescale
profiles of drug and companion diagnostic development programmes.
“Whilst these presentations were focused on Alzheimer’s disease, they also showed how far
protein biomarker research has progressed in personalised medicine for all diseases and the
crucial role played by Proteome Sciences to deliver these results”.
ENDS
For further information please contact:
Proteome Sciences plc
Christopher Pearce, Executive Chairman
Dr. Ian Pike, Chief Operating Officer
Geoff Ellis, Finance Director
Public Relations
IKON Associates
Adrian Shaw
Tel: +44 (0)1932 865065
Email: adrian@ikonassociates.com
Tel: +44 (0)1483 271291
Mobile +44(0)7979 900733
NOTES FOR EDITORS :
1. The three oral presentations at AAIC 2015 were as follows:
I.
Discovery of multiple phosphorylated tau biomarkers in CSF using a novel mass
spectrometry method – Using TMTcalibrator™ this data represents the most
comprehensive profile of low abundant tau peptides and phosphopeptides in CSF
to date. Measuring the phosphorylation status of CSF tau may provide new
diagnostic, prognostic and surrogate biomarkers of drug response for AD.
II.
Microglial - derived proteins in CSF are candidate biomarkers for early diagnosis of
Alzheimer's disease – Utilising the unparalleled sensitivity gains of
TMTcallibrator™ to discover rare microglial derived proteins in CSF. These markers
of neuroinflammation provide new biomarker candidates for very early stage
diagnosis of AD.
III.
Discovering pharmacodynamic biomarkers for disease modifying therapies in
Alzheimer's using different proteomics strategies with a common data analysis
pipeline – SysQuant® and TMTcalibrator™ enable us to study the biggest
challenges of clinical medicine. Using SysQuant® the key processes of AD
pathology in human disease (tau-toxicity) and the reversal of this toxicity in a
mouse model of AD using proprietary CK1d were studied. With a better
understanding of these disease processes, we can then apply TMTcalibrator™ to
hunt for changes in proteins from disease processes in peripheral fluids such as
CSF.
2. How TMTcalibrator™ works:
Hunting low-abundant biomarkers from disease tissue in plasma, CSF and other body
fluids
TMTcalibrator™ is a novel way of hunting for proteins released into body fluids by diseased
tissue. These are the most relevant biomarkers but dilution means they are present at very
low levels. Standard discovery proteomics in body fluids has relatively poor sensitivity and
many tissue-derived proteins are not surveyed. Consequently, most biomarker panels
comprise acute-phase reactant proteins, chemokines and cytokines that often lack
specificity.
TMTcalibrator™ overcomes these limitations by increasing the abundance of tissue
proteins through TMT® isobaric tagging and spiking into body fluids, the key being that the
total protein content from tissue is now substantially greater than that from the fluids.
Once a biomarker panel has been identified, TMTcalibrator™ can be redesigned to provide
a highly accurate absolute quantification assay with internal standard curves in the same
MS/MS spectrum.
3.
The benefits of TMTcalibrator™ :
 Enhanced detection of tissue biomarkers in body fluids
 Detection of low abundant biomarkers missed in standard MS workflow
 Four-point calibration curve for statistical assessment of ion interference
 Allows use of disease-related tissue or cells as surrogate biomarker donor to trigger MS
and boost signal of equivalent marker in body fluid
 Can be combined with a wide range of proteomic workflows e.g. phosphopeptide
enrichment to truly maximize signal enhancement
 Dramatically increases sensitivity of biomarker discovery in complex body fluids with
minimal fractionation
4.
How SysQuant® works:
Next-generation pathway proteomics providing a helicopter view of active cell signaling
and regulatory processes
Personalized Medicine (sometimes referred to as Precision Medicine) could transform
treatment outcomes but requires deeper understanding of disease biology, drug-target
interaction and a system-wide view of mechanisms of action and resistance. Combining
TMT® 10plex labeling with the fastest, most accurate mass spectrometers, SysQuant®
provides the most comprehensive analysis of protein activity across regulatory and
signaling pathways. Application of SysQuant (a global phosphoproteomic profiling
workflow) to tissues and cells enables the identification of new targets and candidate
biomarkers for early diagnosis, drug selection and monitoring of treatment outcomes.
5.
The benefits of SysQuant®:
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Unbiased survey of cell signaling pathways regulated by phosphorylation
Sample multiplexing using TMT® 10plex reagents
High end mass spectrometry using the Orbitrap Fusion Tribrid
~1,000,000 quantitative data points per TMT® 10plex
>8,000 unique protein groups and >12,000 unique phosphorylation sites
Automated annotation of biological features from GO terms, KEGG, Phosphosite Plus,
UniProt & Drugbank
Outstanding bioinformatics and biological interpretation consultancy service
6.
CK1d – out licencing opportunities
Proteome Sciences has excellent toxicity results for two CK1d small molecule tau kinase
inhibitors with in vivo data showing the modification of tau phosphorylation. Application of
the SysQuant® proteomic workflow enabled a comprehensive assessment of the
mechanism of action of these compounds and demonstration of modification of key
pathways linked to amyloid processing. A statistically significant improvement in cognitive
function in a mouse model of AD has also been demonstrated. The CK1d compounds are
available for out licensing.
7.
About Proteome Sciences
Proteome Sciences is a global leader in applied proteomics and peptidomics offering high
sensitivity, proprietary technologies for protein and peptide biomarker discovery, validation
and assay development. The Company is headquartered in Cobham, UK, with laboratory
facilities in London and Frankfurt.
Proteome Sciences’ proprietary research has discovered a large number of novel protein
biomarkers in key human diseases and is focused mainly in neurological/neurodegenerative
conditions and in cancer. It has discovered and patented blood biomarkers in Alzheimer’s
disease, stroke, brain damage and lung cancer for diagnostic and treatment applications
that are available for license or have already been outlicensed.
Hunting for novel protein biomarkers is very challenging and requires dedicated expertise.
Proteome Sciences’ brings over 20 years experience to the problem and our proprietary
workflows including TMT®MS3,SysQuant® and TMTcalibrator™ provide a strong
advantage.
The Company’s PS Biomarker Services™ division provides outsourced proteomics services
and proprietary biomarker assays to pharmaceutical, biotechnology and diagnostics
companies from its ISO 9001: 2008 facility in Frankfurt, Germany.
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