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CMCC 2205

Biomarker panel for the diagnosis of cardiac allograft vasculopathy

Inventors: David Briscoe, Ananth Karumanchi, Michael Seifert, Kevin Daly

Invention Types: Diagnostic/Prognostic, Therapeutics

Research Areas: Cardiovascular/Cardiology

Keywords: Organ Transplant

For More Information Contact:  Caron, Connie

 

Invention Description:

Drs. Briscoe and Daly have developed a panel of biomarkers that can be used to diagnose chronic rejection and cardiac allograft vasculopathy (CAV), an important complication of heart transplantation that frequently limits survival following organ transplantation. Chronic rejection and allograft vasculopathy occurs following several forms of solid organ transplantation, and the prediction of chronic rejection may enable the identification of, as well as the use of therapeutics to halt its development and its progression.

The platform that was used involved the quantitation of endothelial injury and repair as a biomarker of chronic rejection/CAV. Dr. Bricoe's laboratory has studied how the alloimmune response targets graft vascular endothelial cells as a characteristic component of the rejection process. In these studies serum collected from cardiac transplant recipients/patients with and without CAV were used as our index. Serum samples were evaluated using a starndard protein profiler platform. The lab identified 10 molecules that were statistically associated with CAV. By ROC, VEGF-A and VEGF-C were significantly associated with disease. They also generated a classification and regression tree approach (CART) to identify that serum levels of VEGF-A, VEGF-C, along with Angiopoietin-1, and Angiostatin can be used to diagnose CAV with 100% sensitivity and 100% specificity in the study population. The other candidate biomarkers identified include Angiopoietin-2, artemin, urinary plasminogen activator, vasohibin, placenta growth factor, and platelet factor 4. The group is now working on the next iteration, a combination including some of these candidate biomarkers to produce the best combination for the diagnosis or even the prediction of CAV.

Applications:

• A panel of biomarkers, found in human blood, that can be used for the diagnosis of cardiac allograft vasculopathy, a complication which affects heart transplant recipients.
• This panel of biomarkers may be applicable in a modified form to diagnosing allograft vascular disease and/or chronic rejection in other human solid organ transplant receipients.

Competitive Advantages:

• The prediction of chronic rejection may enable the development of, as well as the use of therapeutics to halt its development and its progression.
• Currently the only screening methods for chronic rejection/CAV are invasive.
• Following heart transplantation, patients are scheduled with either coronary angiography or intravascular ultrasound (IVUS), both of which are expensive and highly invasive.
• Biomarker profiles and non-invasive diagnostic tests may be particularly useful in pediatric heart transplant recipients, where invasive techniques are associated with higher adverse event rates or are technically limited by patient size.

Key Publications: Daly KP, et al. VEGF-C, VEGF-A and related angiogenesis factors as biomarkers of allograft vasculopathy in cardiac transplant recipients. J Heart Lung Transplant. 2013 Jan;32(1):120-8.

Daly KP, et al. Vascular endothelial growth factor A is associated with the subsequent development of moderate or severe cardiac allograft vasculopathy in pediatric heart transplant recipients. J heart Lung Transplant. 2017 Apr;36(4):434-442.

IPStatus: Pat. Pend.