Available Technology
A novel assay for improved measurement of factor VIII activity
Technology:
Scientist at the Gilbert lab have been looking into potential mechanisms that may explain the discrepancies between factor VIII activity and correlating PTT values. They found that the difference in reported activity between assays, for some pharmacologic factor VIII products, may be caused through several mechanisms:
1. Factor VIII activity is related to the composition and curvature of supporting membranes. Clinical assays of factor VIII routinely utilize membrane preparations with compositions that do not mimic the cell membranes that support factor VIII function in blood. Thus, the membrane-related activity may differ from activity on physiologic phospholipid membranes and not predict clinical activity.
2. Many inhibitory antibodies which may form over time, target the membrane-binding C domains of factor VIII which is important for phospholipid binding. As a result membrane binding is interrupted and Factor VIII activity is inhibited.
Based on this newly gained knowledge of factor VIII activity using critical characteristics of cell membranes, the Gilbert lab had developed an assay that will be able to predict clinical factor VIII activity and corresponding bleeding risk for these patients.
Markets Addressed
The clotting disorder hemophilia A is caused by impaired or absent function of factor VIII. It is diagnosed using measurements of plasma activated partial thromboplasin time (aPTT) and generation of factor Xa. The extent of the decrease in factor VIII activity is measured by a modified aPTT test or by a two-step test in which factor VIII activity is supported by an artificial membrane source.
Development of antibodies against factor VIII is a common complication of therapy for hemophilia A and can cause acquired hemophilia A in previously normal subjects. Although acquired hemophilia A is associated with a prolonged activated partial thromboplastin time (aPTT), the relative bleeding risk does not correlate well with factor VIII activity levels. Thus there is a need for an improved test for factor VIII activity that more accurately predicts the bleeding risk in patients treated with infused factor VIII and those with inhibitor antibodies against factor VIII.
Innovations and Advantages
This new clinical test for measuring factor VIII activity uses different membrane preparations that recapitulate the relevant features of platelet membranes as they appear within the body. This assay will allow for better prediction of bleeding risk in patients with inhibitory antibodies to factor VIII.
Additional Information
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Inventor(s):
Gilbert, Gary
Lu, Junhong
Novakovic, Valerie A.
Categories:
For further information, please contact:
Michal Preminger, Director of Business Development
(617) 432-0920
Reference Harvard Case #4716