How would you characterize your company’s primary areas of expertise? Transplant Genomics Inc., or TGI, is a molecular diagnostics company committed to improving organ transplant outcomes, with an initial focus on kidney transplant recipients. Working with the transplant community, TGI is commercializing a suite of tests enabling diagnosis and prediction of transplant recipient immune status. The tests are designed to detect early signs of kidney graft injury, differentiate among actionable causes, and enable optimization of therapy, with the potential to extend lives and reduce costs of associated healthcare. Test results will support clinicians with information to optimize immunosuppressive therapy, enhance patient care, and improve graft survival.
The TruGraf Blood Test for kidney transplant recipients uses gene expression profiling to help physicians personalize immunosuppressive therapy. How is it performed? How is it reported? TruGraf is performed on a small amount of blood collected during a patient’s normal blood draw. The draw center will send the patient’s sample to TGI’s CLIA laboratory in Pleasanton, CA, where the test is performed under strict clinical compliance. When the blood sample arrives, the RNA is extracted and analyzed to determine the simultaneous expression levels of multiple genes involved in biological pathways related to immunity in transplantation.
TruGraf results are reported to physicians using the SAFER guidelines to optimize the safe and secure transmission of the electronic communication and management of diagnostic test results. Results reported include a classification of the patient’s immune status with respect to the graft, for example, the probability that the kidney graft is in a state of sub-clinical acute rejection (subAR), clinical acute rejection (cAR), acute dysfunction, no rejection (ADNR), or transplant excellence (TX). Longitudinal results are provided so physicians may monitor patients over time and follow changes in treatment.
How and when was the TruGraf test clinically validated? The TruGraf test relies on gene expression signatures to enable proactive noninvasive serial monitoring, allowing early identification of graft dysfunction and differentiation between clinical rejection and other causes. A host of clinical validation studies have been completed, and others are ongoing.
For example, last May our scientific founders reported in the American Journal of Transplantation a five-center prospective study clinically validating the test. TGI founding scientists demonstrated that gene expression signatures from blood can be used to classify kidney transplant recipients into three diagnostic categories: cAR, ADNR, or TX. The key finding of this study is that gene expression profiling can be used to differentiate between cAR and ADNR in patients with elevated creatinine levels with high predictive accuracy.
A study was recently presented at the American Transplant Congress that evaluated the feasibility of graft monitoring via profiling using RNA sequencing. In this study, Drs. Friedewald, Kurian, and colleagues demonstrated the use of RNA sequencing as an alternative data generation platform for analyzing gene expression profiles in blood and tissue from kidney transplant recipients. The data validated that gene expression signatures for subAR, cAR, and TX can be detected as robustly with RNA sequencing as with microarrays. Next-generation sequencing has the potential to offer advantages such as reduced cost of analysis and improved throughput for sample processing.
Do these results speak to the possibility of opening up economies of scale in lab operation and making kits that could be distributed globally? In the near term, RNA sequencing offers the opportunity to perform these assays at lower cost and higher throughput, reducing turnaround time. Development of kits enabling assay performance on local lab-based sequencing systems would facilitate expansion of test use worldwide. Such kits would initially be sold as research use only (RUO) products until sufficient validation studies are completed to support regulatory approval.
I understand you are a kidney transplant recipient yourself. How did your personal experiences lead you to become a founder and director of TGI? As a 2011 kidney transplant recipient, among my first concerns were how to manage the complex immunosuppressive drug regimen and how to avoid risk of infection. While nearly every problem in transplantation is treatable if detected early enough, testing approaches at the time—and still today—did not detect a problem until it was already serious.
Serum creatinine, the biomarker which has been used to monitor kidney transplant recipients for the past 30 years, is an insensitive, late-trailing indicator of dysfunction. By the time a rise in creatinine is evident, damage to the kidney has already occurred, and even then the cause of dysfunction remains to be determined. So a rise in serum creatinine is really a trigger to biopsy. Biopsies are expensive, painful, and not well suited for frequent monitoring.
Having said that, I really only became aware of the advances in transplant biomarker discovery and validation through an article that appeared in a journal in 2012. I immediately searched the NIH grants database to find out who was actively working on this problem and quickly found that Dr. Abecassis and Dr. Salomon were leaders in the field. Their unbiased approach to discovery and validation of genomic biomarkers for kidney graft status, which embraced the complexity of the underlying biology, resonated with my experience as a molecular biologist. We all believed that routine tests could be developed based on genomic analysis to detect signatures in blood that indicate early signs of rejection. Together we founded TGI.
