Mass Spectrometry

The PrecivityAD® test aims to help physicians better determine the presence or absence of amyloid plaques in the brain, one of the hallmark signs of Alzheimer’s disease. A critical part of this innovation is the mass spectrometry-based technique employed by C₂N. 

A mass spectrometer is a device that produces charged particles (ions) from biological substances and biomarkers present in complex tissues and fluids like blood. The platform then uses electric and magnetic fields to measure the mass of the charged particles. 

Mass spectrometry has dramatically grown in use over the past decade as a precise analytical tool that identifies compounds based on the mass(es) of their molecular components, fragments, and their charge state(s). This has significant implications for the field of clinical diagnostics.

When used in blood tests to detect pathological markers of Alzheimer’s disease, mass spectrometers provide high analytical specificity. This technology is providing greater levels of accuracy in pathological identification that scientists are harnessing for needed breakthroughs in medicine, such as in the field of Alzheimer’s disease. Researchers are also using it to detect the presence of COVID-19 proteins/peptides in human biofluids. 

Mass spectrometry has high sensitivity and specificity for detecting and quantifying known and novel low abundance biomarkers in blood products.

For additional information on Mass Spectrometry, please visit the American Society for Mass Spectrometry at https://www.asms.org/about-mass-spectrometry.

Stable Isotope Spike Absolute Quantification
(SISAQ™ Platform)

The Stable Isotope Spike Absolute Quantitation (SISAQ™) platform is a proprietary C₂N technique that enables the measurement of the absolute concentration of peptides in biological fluids. This mass spectrometry (MS) based technique identifies peptides with a very high degree of specificity and precision in the concentration measurement. The proteomic applications for this technique are numerous and an important complement to and can be performed concurrently with C₂N’s kinetic SILK™ assay, eliminating the need for separate ELISA assays. Studies performed at C₂N have shown that the SISAQ™ assays have less variability in the measurement of Aβ compared to ELISAs.

The SISAQ™ platform is used for measuring Aβ42/40 in plasma samples for the PrecivityAD® blood test to assess brain amyloidosis.

Stable Isotope Labeling Kinetic (SILK™ Platform)

For the stable isotope labeling kinetic (SILK™) platform, we infuse a stable, non-radioactive isotope labeled amino acid into human subjects. In C₂N’s flagship product, the SILK-Aβ® assay, 13C6 leucine is used, since it is an essential amino acid and readily crosses the blood brain barrier. The stable isotope incorporates into newly made proteins in the brain, which we sample through serial collection of various biological fluids. C₂N offers a number of SILK™ and SISAQ™ platforms for measuring specific proteins in both cerebrospinal fluid and plasma.

Advantages of the SILK™ platform:

Highly sensitive: Highly sensitive biomarker measurements allow for fewer subjects and better powered studies to detect important biologic differences between drug study arms. The SILK-Aβ® assay is highly sensitive for identifying drug-induced changes of Aβ metabolism.

Target validation: The SILK™ method directly measures the metabolism of the biomolecule of interest, even if multiple isoforms are present. This dynamic endpoint is notably more informative than static measurements of the concentration of proteins. The SILK™ assay allows for novel therapeutic target validation and new insights into the mechanism by which drugs exert their biologic effects.

Speed and lowered cost: Measurements of protein metabolism allow for quick endpoint read-outs and the identification of drug activity signals more rapidly than clinical and imaging endpoints (i.e., days versus months or years). In collaboration with industry partners, we seek to terminate undeserving compounds early and streamline promising candidates rapidly into later-stage clinical development. The results are improved efficiency and lowered overall costs of clinical drug development.

Approach to Drug Development

Our vision is to develop and catalyze the discovery of novel mechanism-based therapeutics to slow or halt the progression of neurodegenerative diseases.

We have developed a portfolio of anti-tau antibodies (including ABBV-8E12) for the treatment of Alzheimer’s disease and other neurological disorders, and in March 2015, C₂N formed a global partnership with AbbVie to develop and commercialize these antibodies.

Using our proprietary Stable Isotope Labeling Kinetic (SILK™) platform, we can measure the production and clearance of peptides, proteins and other biomolecules directly in the plasma, spinal fluid and brain of humans and animals. This capability helps identify, develop, and optimize new molecules that target the key biologic mediators of pathogenesis for diseases like Alzheimer's, Parkinson's Disease, Huntington's Disease, and others.