The assembly of pathogenic complexes, broadly described as “plaques”, causes a number of chronic degenerative diseases, including Alzheimer’s disease (AD) and atherosclerosis. A classic example is the development of atherosclerotic plaque in the walls of blood vessels, which is believed to begin during early childhood and continues asymptomatically throughout middle age. As patients age, they develop a number of chronic cardiovascular complications due to the progressive growth of the atherosclerotic plaque. There is a clear need for discovering new treatment modalities and effective diagnostic methods to care for individuals with neurodegenerative and cardiovascular diseases. Unlike the detection of microorganisms and viruses by various methods, the detection of atherosclerotic and amyloid plaque particles related to cardiovascular or neurodegenerative diseases remains a scientific challenge and a bottleneck in discovering disease-modifying drugs and effective diagnostic methods. Our proprietary Plaque Array platform removes this bottleneck both for accelerating drug discovery and developing diagnostic methods.
The Plaque Array is a combination of flow cytometry and a proteomics-based serum biomarker identification method (Fig. 1). By applying a mass spectrometry-based proteomics approach, we have generated a database with signatures of serum proteins that contribute to the process of forming different types of plaque particles. The biomarker database aids in identifying serum proteins that overlap as well as those unique to amyloid beta protein (abeta), cholesterol, tau and α-synuclein plaque particles. We apply the Plaque Array technology for clinical diagnosis, personalized medicine and drug discovery for plaque-related diseases.
The above figure is a schematic representation of the flow cytometry- and mass spectrometry-based detection, sorting and proteomics analysis of plaque particles. Step 1, the in vitro formation of insoluble plaque particles in serum; step 2, cell sorter-based identification and isolation of fluorescent particles; step 3, trypsin digestion of the isolated plaque particles to prepare peptide fragments and step 4, mass spectrometry-based (MS/MS) proteomics for the identification of blood biomarkers.
PLAQUE ARRAY™ clinical diagnostic services
- Clinical diagnosis based on the discovery of accelerated in vitro formation of amyloid and atherosclerotic plaque particle in serum
- Indicated for the rapid identification and stratification of patients with atherosclerosis and AD
- Flow cytometry-based non-invasive detection method using small volumes of serum/plasma samples
- High reproducibility, low cost and validated in clinical samples
- Pre-screening of patients for clinical studies and the evaluation of drug efficacy in atherosclerosis and AD patients
PLAQUE ARRAY™ drug discovery and screening services
- Unique and innovative platform for the rapid detection of various plaque particles in patient serum samples
- Mimics the in vivo processes that occur in AD, atherosclerosis and other plaque related diseases
- Targets a novel mechanism of accelerated atherosclerotic and amyloid plaque formation to discover effective anti-plaque drugs
- High throughput screening of chemical or protein libraries to rapidly identify leads
- Employs FACS-based screening to analyze drug efficacy against plaque-induced pathological pathways (inflammation, apoptosis, cell proliferation and oxidative stress) at the single and multiple cell levels
- Detects the development of atherosclerotic and amyloid plaques in preclinical mouse models