PLAQUETEC LTD (‘PlaqueTec’) today announced the publication of the first peer‐reviewed article demonstrating the feasibility and potential of the PlaqueTec Liquid Biopsy System™ (LBS) to detect biomarkers for coronary artery disease (CAD). The open‐access article, appearing online in the 1 December 2017 issue of the Journal of the American College of Cardiology [JACC]: Basic to Translational Science, reports results from the first‐in‐human studies of the LBS in detecting biomolecular gradients in diseased coronary arteries of symptomatic patients undergoing percutaneous coronary intervention (PCI) procedures.
The PlaqueTec LBS™ is the first product approved in the European Union for collecting biomarkers directly associated with plaques within coronary arteries, as a means to assess ‐‐ and potentially resolve ‐‐ residual inflammatory risk. It is the first and only dedicated liquid biopsy catheter that can be deployed at the site of coronary plaque to assess risk.
“The LBS fills an unmet clinical need to detect coronary atherosclerotic plaques that are likely to rupture and therefore precipitate acute coronary syndromes,” explained lead author Nick E.J. West, MA, MD, FRCP, Chief Medical Officer of PlaqueTec and an interventional cardiologist at Papworth Hospital, Cambridge, UK. “This innovative catheter enables, for the first time, the definition of a biochemical signature for vulnerable plaques in living patients. Our experiments suggest that the LBS may facilitate identification of prognostic biomarkers and development of surrogate endpoints for future clinical trials.”
Dr. West and colleagues analyzed data from the first‐in‐human safety and feasibility study and the first human proof‐of‐concept evaluation of the LBS (n=58). The LBS was used as an adjunct to coronary angioplasty and stent deployment in patients with stable angina pectoris or stabilized non‐ST‐segment elevation acute coronary syndromes (ACS). The system draws blood samples from the ‘boundary layer,’ close to the vessel wall, where biomolecules released from plaques are likely to be most concentrated. It can also detect small gradients of released molecules by simultaneously collecting blood both upstream and downstream of individual plaques.
Deployment of the LBS into unobstructed coronary arteries and its use in taking four simultaneous blood samples was shown to be feasible and safe in patients undergoing angioplasty to a target in a different coronary artery. In unobstructed vessels with no lesion, the investigators observed no significant gradients of 92 biomolecules involved in the CAD process. In contrast, they observed statistically significant gradients of bioactive molecules across intact and disrupted atherosclerotic plaques, implying the release of substances from plaques into the boundary layer of the vessel. The investigators detected several inflammatory mediators, consistent with the inflammatory status of the endothelium.
After angioplasty, the investigators observed the release of additional substances, including matrix metalloproteinase‐12 (MMP12), which is normally undetectable in endothelial cells or smooth muscle cells and expressed only around the core of vulnerable plaques. Due to the causative role of MMP12 in early strokes and its association with subsequent strokes and major adverse events, the investigators surmised that the post‐angioplasty gradient of MMP12 may yield important diagnostic or prognostic information.
“This paper validates the feasibility of using the LBS to generate scientifically and clinically valuable information that may improve risk assessment and facilitate earlier intervention in patients with coronary artery disease,” said Annalisa Jenkins, MBBS, FRCP, Chief Executive Officer of PlaqueTec. “In the future, the system may be used to sample across multiple sites of disease in a patient’s coronary artery to highlight the biologically active areas at highest risk of disease progression. The signals that are found may inform the development of new assays and treatments. Although much remains to be done in defining the optimal biochemical signatures to predict patient risk, our proof‐of‐concept studies support the path forward.”