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Profiling circulating fragments of fibrillin-1, fibrillin-2, and fibulin-4 as biomarkers for disease

 

OHSU # 1390

Summary:

Technology Overview

Fibrillin-1, fibrillin-2, and fibulin-4 are molecular components of elastic fibers and microfibrils. Elastic fibers and microfibrils are stable structures especially abundant in the connective tissues of blood vessels, lung, skin, ligaments and tendons, and the eye. As a result of disease processes, these structures can be degraded by proteases. Examples of diseases that exhibit degradation of elastic fibers and microfibrils are Marfan's syndrome (a heritable disorder of connective tissue affecting 1 in 5,000), aortic aneurysm and aortic dissection (major health issues in the general population), and scleroderma. As many diseases involving the degradation of elastic fibers and microfibrils present few obvious symptoms, a simple test, such as a blood test, would be highly desirable to increase the rate of early detection and to facilitate monitoring of disease progression.

To meet the need for simple and relatively inexpensive methods for detecting the degradation of elastic fibers and/or microfibrils, and their associated disease, OHSU has developed methods for detecting and monitoring the circulating concentration of elastic fiber and/or microfibril fragments. In particular, several modified sandwich ELISAs have been developed that can detect fragments of elastic fiber and microfibril proteins fibrillin-1, fibrillin-2, and fibulin-4. The assays of the present invention are useful to identify the degradation of elastic fibers and/or microfibrils, to measure the rate at which degradation (and fragmentation) is proceeding over time, and to determine whether treatments slow the rate of degradation. The potential value of these assays is significant as diseases associated with degradation of elastic fiber and microfibrils can result in extensive health problems.

Market Summary

There are currently no commercially-available assays to measure circulating fragments of elastic fibers and microfibrils.

The assays for osteoporosis that measure bone collagen telopeptide breakdown products are the most successful. Beyond osteoporosis, the use of connective tissue biomarkers for disease has not been broadly investigated.

Current methods for detecting and monitoring diseases related to degradation of elastic fibers and microfibrils are relatively complex and expensive. In addition, progression of an aortic aneurysm is currently monitored using expensive imaging modalities and is measured by the incremental dilation of the aortic wall. Although such imaging can provide an indication of the growth of an aorta, the costs associated with this technique are substantial. Because of these limited detection and monitoring methods, aneurysms often go undetected until rupture occurs, resulting in severe pain, massive internal hemorrhage, and often death.

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For more information, contact:

Travis Cook
Senior Technology Development Manager
503-494-3229