A Novel Point-of-Care Rejection and Immunosuppression Monitoring Assay (PRIMA) for Vascularized Composite Allotransplantation (VCA)
Abstract
Trauma is common in both military and civilian settings, and burns, amputation, and other non-salvageable tissue injuries can significantly impact form and function. Vascularized composite allotransplantation (VCA) involves transplants of multiple tissues such as muscle, bone, nerve, and skin as functional units). VCA can serve to replace lost or damaged tissue following a traumatic event and can have a significant impact on the restoration of form and function. VCA has gained increasing importance in clinical practice and may evolve into an important component of multidisciplinary approaches to reconstruction after severe injuries. To date, sources have reported as many as 150 upper extremity and 40 face transplants performed worldwide. VCA such as hand or face transplants require life-long immunosuppressant drugs, so the transplant is not rejected. Tacrolimus is an FDA-approved drug used in majority of VCA protocols. Too much immunosuppression with tacrolimus can lead to kidney damage (requiring kidney transplantation), cancer, or infections, and too little immunosuppression can increase risks of transplant rejection. Timely diagnosis and treatment of acute and chronic rejection is also equally important to ensure graft survival. In order to improve life enhancing benefits of VCA in VCA, the risks of lifelong, high-dose or multi-drug systemic immunosuppression must be reduced but also rejection has to better managed. It is thus critical to frequently monitor drug levels of tacrolimus, as well as levels of markers of kidney function in VCA patients, but also be able to predict when rejection episodes may occur or how severe they may be when they happen so that they receive the right dose of tacrolimus to help grafts to survive without the risk of adverse effects on the kidney. Current methods of laboratory monitoring of tacrolimus level and kidney markers require complicated or costly tests that are time-consuming and require patients to access special laboratories. This may cause missed laboratory tests/visits or even delayed reporting of results such as drug levels leading to improper management of patients with increased risk of toxic side effects. The PRIMA technology will combine measurements of key inflammation biomarkers with immunosuppressant drug levels and early kidney function biomarkers in an integrated, easy-to-use, point- of-care device that uses a tiny amount of fingerstick sampling of blood, similar in format to a glucose meter. Our technology builds on our experience with other rapid assays in VCA for immunosuppressant drug levels that have confirmed their accuracy in prior studies. When combined with kidney damage and inflammation markers, this technology will help to both identify rejection episodes early and follow treatment to limit rejection and toxicity. Our PRIMA technology will help to both individualize drug treatment as well as predict rejection risk to limit drug toxicity and immunologic attrition of the graft. The ease of use, low cost, and rapid analysis enabled by the proposed technology represents a significant advancement to better enable monitoring and optimization of immunosuppressant drug levels, protocol adherence, and treatment progression. Improving adherence and optimizing existing immunosuppressant drug protocols is a near-term goal that we believe can be impactful as a means to reduce long term toxicity of immunosuppression and improve the safety and efficacy of protocols.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310600
Entities
People
- Trong Nguyen
Organizations
- United States Army