Detection of early stage Vascular Calcification

Summary

A non-invasive and inexpensive assay for detection and diagnosis of early  vascular calcification (VC).  Specific components of the patient’s blood are isolated and analysed for molecular markers indicative of early-stage VC.  A clinical calcification risk and progression score can  then be calculated, thus facilitating early detection and treatment.

 

Technology Overview

VC, as measured by the Coronary Artery Calcium (CAC) score, is an established independent predictor of cardiovascular disease (CVD) risk. It is an increasingly important clinical concern, particularly for sufferers of chronic kidney disease, type 2 diabetes and atherosclerosis.  This pathological process is characterised by the deposition of calcium phosphate salt crystals in the arterial intima and/or media, which stiffens the vascular wall.  Calcified vessels are less compliant and cannot efficiently supply oxygenated blood to the heart, increasing the risk of heart attack and stroke, if left untreated.  The CAC score, as determined by EBCT or MDCT, is the established independent predictor of CVD risk. However these techniques are expensive, time-consuming; require access to specialist imaging equipment; expose subjects to a relatively high dose of radiation, which is difficult to justify in a screening tool and detect VC at a relatively late stage when it is already clinically observable.

Hence there is a clear need for a diagnostic for VC which can be used to i) provide early indication of CVD in high risk patient groups, ii) monitor VC status in high risk patient groups and iii) stratify patients for alternative hyperphosphataemia therapies for whom calcium-based phosphate binders are inappropriate. 

Prof Shanahan and her group have shown that VC is initiated in nodules by release of apoptotic bodies and matrix vesicle-like structures from VSMCs that act as a nidus for hydroxyapatite nucleation, and that extracellular calcium and phosphate are key regulators of matrix vesicle (MV) mediated calcification.  These matrix vesicles establish the first niches of mineralisation early in the process. These MVs are not only present in the vessel wall but also in the blood of individuals. They have identified that there is a correlation between the levels of certain vesicular compounds (calcium and calcium phosphate salt) in these MVs (exosomes), in the blood of an individual and that individual’s risk of having or developing VC.

Figure: Quantitative determination of calcium  in exosomes obtained from blood of patients with diabetes type 2

(AK12C; AK13C and AK16C); diabetes type 1 (AK17C) and healthy individuals (AK14 and AK15).

 

Benefits

The test could be used for 

  • initial assessment of CVD risk in high risk patient groups such as CKD and type II diabetes. 
  • ongoing monitoring of CVD risk in high risk patients groups.
  • stratification of hyperphosphataemia patients to identify those requiring second-line non-calcium-based treatments e.g end stage renal disease patients.


Opportunity

Currently seeking a development partner and/or licensee for this opportunity.


Patent Status

 UK priority application was filed on 15/02/2010 

US granted patent US 8,993,247 Grant date 31/03/2015

EP application pending

 

King’s ref no. IP501/0554

 

 

 

 

 

Patent Information:
Category(s):
Diagnostics
For Information, Contact:
Salma Ishaq
IP & Licensing Manager
King's College London
salma.ishaq@kcl.ac.uk
Inventors:
Catherine Shanahan
Aleksandr Kapustin
Keywords: