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TECHNOLOGY – PRINCIPLE

From disease …
Misfolded and aggregated proteins that are characteristic for neurodegenerative diseases (e.g. α-syn for Parkinson’s, tau and amyloid-β for Alzheimer’s disease) can be utilised as biomarkers. Similar to prions, disease-related misfolded proteins transfer their misfolded structure upon contact to correctly folded partner proteins, a mechanism that is known as ‘seeding’. This results in elongated aggregates that accumulate in the brain leading to an impairment of neuronal functions. This is a key driver for the formation of various neurodegenerative diseases.


… to diagnostic
Our assay exploits the pathological mechanism for its detection principle. The misfolded proteins behave as ‘seeds’ and induce aggregation of the same natively folded protein that can be produced recombinantly. These aggregates are visualized by a fluorescent dye and are subsequently broken up by shear forces into many new seeds. The cycle then restarts and enables cyclic seed amplification. This chain reaction, akin to PCR but using protein as a substrate, results in the detection of seeds with high sensitivity and specificity.

TECHNOLOGY – THE SEEDCYCLER®


„SeedCycler®“

The „SeedCycler®“ is an in-house developed PCR Thermocycler-sized medical device equipped with rotating magnets to generate and adjust shear forces as well as a laser to detect fluorescent signal of the protein aggregates. Corresponding reaction vessels (AmpliStripe®) of special design made by injection molding allow for optimal fluid flow and shear force. Recombinantly expressed and purified proteins of the respective biomarkers fuel the reaction. In the final step, data analysis, data mining and cluster analysis allow for the identification of different biomarkers and disease strains.
The combination of our in-house developed SeedCycler®, reaction vessels AmpliStripe® and reaction buffers enable a resource- and time-efficient detection for various neurodegenerative diseases.

Our assay exploits the pathological mechanism for the detection principle.

The misfolded proteins behave as „seeds“ to convert and aggregate freshly made recombinant proteins that we add. The aggregates are visualized by a fluorescent dye. Then the aggregates are disrupted by shear forces into many new seeds. The cycle restarts and gives a cyclic amplification: A chain reaction similar to PCR, but with proteins. This results in high sensitivity and specificity.

The technology has been patented and reviewed by independent scientists.

TECHNOLOGY – APPLICATIONS

Immediate detection using the seeding disease mechanism rather than indirect methods based on e.g. antibodies (ELISA). Direct readout of interfering substances for drug screening.

Exponential amplification to provide high sensitivity for detection of early-stage disease in different body fluids like CSF or blood.

An early diagnosis of neurodegenerative diseases is crucial for prevention or delay of disease onset, as appearing symptoms indicate an already irreversible neuronal damage

OUR SERVICE PORTFOLIO

» Services for drug research
Protein aggregation assays with quantitative analysis of protein seeding activity and dynamics, as a function of shear force, compound and protein seed concentration. Applications for identifying active protein seeding inhibitors in relevant patient cohorts based on aggregate strains/sub-types.

» Smart Trials: In-vitro diagnostic for clinical trials
Analysis of human CSF to characterize clinical trial patients. Identify patient cohorts based on disease-associated aggregate types and patient sub-types, that are reflected in inclusion/exclusion criteria for the trial, monitor disease progression and development of co-pathologies.

» Recombinant Proteins
We offer recombinantly produced monomers for several of the biomarkers of neurodegenerative diseases like α-synuclein, human tau, amyloid-β. Please ask us for a quotation depending on your needs on amount and purity.