Quantcast

Industry news that matters to you.  Learn more

ViveBio, LLC Enters Worldwide Exclusive Licensing Agreement with Renovar Inc. for Novel Urine-based Biomarker Technologies Covering Kidney Disease and Transplant Monitoring

ViveBio, LLC recently announced that it has signed a worldwide exclusive licensing agreement with Renovar, Inc. for urine based biomarkers to predict and monitor kidney diseases as well as rejection in transplant recipients. Based upon unique inflammatory protein signatures found in the urine of diseased or injured kidney’s, the Renovar technology can be used to assess the health of a patients kidney’s, guide therapeutic decision making and help stratify patients by risk for developing acute rejection.

Transplant Genomics Inc. Announces Exclusive License to Patent Rights Co-Owned by The Scripps Research Institute and Northwestern University

Transplant Genomics Inc. (TGI) announced that it has obtained an exclusive license to patent rights co-owned by The Scripps Research Institute and Northwestern University that provide the foundation for clinical tests to improve management of organ transplant recipients, with the potential to extend lives and reduce costs of associated healthcare. TGI intends to develop and commercialize tests that use genomic markers of transplant graft status as part of a surveillance program to detect and respond to early signs of graft injury.

Researchers Develop Rapid, Cost-effective Early Detection Method for Organ Transplant Injury

A recently reported blood test for the early detection of organ transplant injury could enable more timely therapeutic intervention in transplant patients and thus help to avoid longer term damage. As described by scientists at the University Medical Center Göttingen and Chronix Biomedical, a molecular diagnostics company, the new method uses Bio-Rad Laboratories’ Droplet Digital PCR (ddPCR™) technology to overcome the obstacles of earlier tests, which were both time-consuming and costly. The method was presented at the American Association of Clinical Chemistry (AACC) 2013 annual meeting and has been accepted for publication in Clinical Chemistry.

Approximately 28,000 organ transplantations (known as grafts) are performed each year in the U.S., with another 100,000 patients on waiting lists. However, transplant patients are often subject to organ rejection: acute rejection of liver transplants within three years is nearly 22 percent, while heart and lung rejection is close to 50 percent. In addition, nearly half of all of kidney transplants fail within 10 years.

Graft-derived cell-free DNA (GcfDNA) in the circulation of transplant recipients is a potential rejection biomarker. But previous attempts to determine GcfDNA, which require parallel sequencing of donor and recipient DNA, are expensive and require a long turnaround and use of donor DNA. University Medical Center Göttingen and Chronix Biomedical researchers sought to develop a new method in an attempt to address these drawbacks.

Using ddPCR for Fast, Cost-Effective Test

The researchers applied Bio-Rad’s ddPCR technology to quantify graft-derived cfDNA in recent liver transplant patients and in stable patients who had undergone a transplant procedure more than six months earlier. ddPCR technology allowed them to develop a cost-effective and fast laboratory test that detects cfDNA being released into the blood stream by dying cells from the transplanted organ.

“GcfDNA from dying graft cells are the most direct and sensitive indicator of organ rejection and we needed an instrument that could measure it,” said Chronix Biomedical’s Chief Technology Officer and the study’s senior author, Ekkehard Schuetz, MD, PhD. “ddPCR added an additional level of reliability and precision to traditional PCR.”

Sequencing methods typically require batch sampling, but by using ddPCR, researchers are able to run single samples. Additionally, this method is reducing test time from three days or more to one day and costs by 90 percent. The study authors were able to address the need for donor DNA by preselecting SNPs that ensure enough heterogeneity between donor and recipient. The new blood test can also deliver results up to several days before the conventional aspartate aminotransferase (AST) and bilirubin tests for liver transplantation rejection, with the potential for an immediate positive impact on patient care.

“We will now be able to detect subclinical rejection and early intervention may allow us to avoid a full-blown rejection,” said Michael Oellerich, M.D., FACB, FRCPath and Lower Saxony Distinguished Professor of Clinical Chemistry at the University Medical Center Göttingen and study Principal Investigator. “This test may be useful to personalize immunosuppression and to improve long-term outcomes.”

“Detecting non-host cfDNA is the third example for the commercial potential of cfDNA diagnostics. Researchers will now be able to extend the applications from fetal cfDNA in maternal blood and personalized biomarkers for minimal residual disease in cancer to solid organ transplantation,” said Howard Urnovitz, PhD, Chronix Biomedical’s Chief Executive Officer.

“We are looking forward to the improvements in precision medicine we can offer with ddPCR and this example in transplantation highlights the diagnostic value for the technology,” said Paula Stonemetz, Director Diagnostic Business Development, Digital Biology Center, Bio-Rad Laboratories.

The researchers were awarded a National Academy of Clinical Biochemistry (NACB) Distinguished Abstract Award at the 2013 AACC annual conference. The results are part of a larger planned study to determine if cfDNA is the earliest indication of a transplant organ rejection.

Source: EurekAlert!

Urine Biomarker Test Can Diagnose as well as Predict Rejection of Transplanted Kidneys

A breakthrough non-invasive test can detect whether transplanted kidneys are in the process of being rejected, as well as identify patients at risk for rejection weeks to months before they show symptoms, according to a study published in The New England Journal of Medicine (NEJM).

By measuring just three genetic molecules in a urine sample, the test accurately diagnoses acute rejection of kidney transplants, the most frequent and serious complication of kidney transplants, says the study’s lead author, Dr. Manikkam Suthanthiran, the Stanton Griffis Distinguished Professor of Medicine at Weill Cornell Medical College and chief of transplantation medicine, nephrology and hypertension at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

“It looks to us that we can actually anticipate rejection of a kidney several weeks before rejection begins to damage the transplant,” Dr. Suthanthiran says.

The test may also help physicians fine-tune the amount of powerful immunosuppressive drugs that organ transplant patients must take for the rest of their lives, says Dr. Suthanthiran, whose laboratory developed what he calls the “three-gene signature” of the health of transplanted kidney organs.

“We have, for the first time, the opportunity to manage transplant patients in a more precise, individualized fashion. This is good news since it moves us from the current one-size-fits-all treatment model to a much more personalized plan,” he says, noting that too little immunosuppression leads to organ rejection and too much can lead to infection or even cancer.

Given the promise of the test first developed in the Suthanthiran laboratory at Weill Cornell and previously reported in NEJM, the National Institutes of Health (NIH) sponsored a multicenter clinical trial of nearly 500 kidney transplant patients at five medical centers, including NewYork-Presbyterian/Weill Cornell Medical Center and NewYork-Presbyterian/Columbia University Medical Center. The successful results of that trial are detailed in the July 4 issue of NEJM.

Such a test is sorely needed to help improve the longevity of kidney transplants and the lives of patients who receive these organs, says study co-author Dr. Darshana Dadhania, associate professor of medicine and medicine in surgery at Weill Cornell Medical College and associate attending physician at NewYork-Presbyterian Hospital.

Dr. Dadhania says that the primary blood test now used to help identify rejection — creatinine, which measures kidney function — is much less specific than the three-gene signature.

“Creatinine can go up for many reasons, including simple dehydration in a patient, and when this happens we then need to do a highly invasive needle-stick biopsy to look at the kidney and determine the cause. Our goal is to provide the most effective care possible for our transplant patients, and that means individualizing their post transplant care,” she says. “Using an innovative biomarker test like this will eliminate unnecessary biopsies and provide a yardstick to measure adequate immunosuppression to keep organs — and our patients — healthy.”

Although a number of researchers have tried to develop blood or urine-based tests to measure genes or proteins that signify kidney organ rejection, Dr. Suthanthiran and his research team were the first to create a gene expression profile urine test — an advance that was reported in NEJM in 2001 and, with an update also in NEJM, in 2005.

The research team measured the levels of messenger RNA (mRNA) molecules produced as genes are being expressed, or activated, to make proteins. To do this, they developed a number of sophisticated tools to measure this genetic material. “We were told we would never be able to isolate good quality mRNA from urine,” he says. “Never say never.”

He and his colleagues found that increased expression of three mRNAs can determine if an organ will be, or is being, rejected. The mRNAs (18S ribosomal (rRNA)–normalized CD3ε mRNA, 18S rRNA–normalized interferon-inducible protein 10 (IP-10) mRNA, and 18S rRNA) indicate that killer T immune cells are being recruited to the kidney in order to destroy what the body has come to recognize as alien tissue.

The signature test consists of adding levels of the three mRNAs in urine into a composite score. Tracked over time, a rising score can indicate heightened immune system activity against a transplanted kidney, Dr. Suthanthiran says. A score that stays the same suggests that the patient is not at risk for rejection.

“We were always looking for the most parsimonious model for an organ rejection biomarker test,” Dr. Suthanthiran says. “Minimizing the number of genes that we test for is just more practical and helps to give us a clearer path towards diagnosis and use in the clinic.”

Physicians can tailor a patient’s use of multiple immunosuppressive drugs by lowering the doses steadily, and monitoring the patient’s composite score over time. Any increase would suggest a somewhat higher dose of therapy is needed to keep the organ safe.

“This is akin to monitoring blood glucose in a patient with diabetes,” Dr. Suthanthiran says. “Because different people have different sensitivity to the two-to-four immunosuppressive drugs they have to take, this test offers us a very personalized approach to managing transplantations.”

Predicting rejection weeks before it happens

The clinical trial began in 2006 with participation from five medical centers — NewYork-Presbyterian/Columbia University Medical Center, the University of Pennsylvania’s Perelman School of Medicine, the Northwestern University Feinberg School of Medicine, the University of Wisconsin School of Medicine and Public Health and NewYork-Presbyterian/Weill Cornell Medical Center, which contributed 122 of the total 485 kidney transplant patients.

The gene-expression studies were led by Dr. Suthanthiran with his laboratory serving as the Gene Expression Monitoring (GEM) core and the clinical trial was led by Dr. Abraham Shaked, director of the PENN Transplant Institute at the Perelman School, on behalf of the Clinical Trials in Organ Transplants 04 (CTOT-04) Study Investigators. The GEM core was blinded to the clinical status of the patients including their biopsy results and the data collection and analysis were performed by an independent statistical center sponsored by NIH.

Researchers collected 4,300 urine specimens during the first year of transplantation, starting at day three post-transplantation. The urine samples were shipped to the GEM core at Weill Cornell Medical College, where analysis of the urine revealed that the three gene-based biomarkers signature could distinguish kidney recipients with biopsy confirmed rejection from those whose biopsies did not show signs of rejection or who did not undergo a biopsy because there was no clinical sign of rejection.

The researchers used the signature to derive a composite score and identify a threshold value indicative of rejection. This score accurately detected transplant rejection with a low occurrence of false-positive and false-negative results. “It is about 85 percent accurate, which is much higher than the creatinine test used today,” Dr. Suthanthiran says. Investigators then validated the diagnostic signature by obtaining similar results when they tested a set of urine samples collected in a separate CTOT clinical trial.

Dr. Suthanthiran anticipates conducting another NIH-funded clinical trial to test whether the signature test can be used to personalize individual immunosuppressive therapy. He says that NIH is also interested in submitting the test to the federal Food and Drug Administration for approval.

These studies have provided enough information that many medical centers can test their own kidney transplant patients for rejection using the publicly-available formula for the biomarker test. Dr. Suthanthiran also is working to develop a way for patients to submit samples via mail for biomarker testing, and avoid an office visit. The study was supported by NIH grants UO1AI63589 and R37AI051652, the Qatar National Research Foundation (NPRP 08-503-3-111) and by a Clinical and Translational Science Center Award (UL1TR000457, to Weill Cornell Medical College).

Study: Urinary-Cell mRNA Profile and Acute Cellular Rejection in Kidney Allografts

Source: Weill Cornell Medical College

Biomarker Predicts Organ Rejection and Death in Heart Transplant Patients

Critical Diagnostics announced recently the recently-published results of a Utah Transplantation Affiliated Hospitals Cardiac Transplant Program study involving the use of a novel biomarker, ST2, to monitor heart transplant patients for rejection. Subjects with the highest levels of ST2 had a more than 3-fold increase in the risk for death than those with the lowest ST2 levels. Moreover, this risk was present early and sustained from the time of initial blood draw to many years forward.

Just over 45 years ago, on December 3, 1967, Dr. Christian Barnhard transplanted the first human heart into 53-year old Lewis Washkansky, a South African grocer dying of chronic heart disease. After his surgery, Washkansky was given drugs to suppress his immune system, but they also left him vulnerable to deadly infections. He died 18 days later from double pneumonia.

Medicine has come a long way since then. Worldwide, over 3,500 heart transplants are performed annually, more than half in the U.S. Post-transplant survival rates now average 15 years, yet rejection and death are still all too common.

Currently, biopsy-driven diagnoses are used to predict transplant organ rejection, but this type of procedure is costly, involves risk, and offers little consideration of the underlying biological processes that predict the presence or severity of rejection and/or likelihood of adverse consequences.

In the ST2 study (“Interleukin receptor family member ST2 concentrations in patients following heart transplantation”), a total of 241 transplant patients were followed for a period of just over 7 years, during which time there were 62 deaths, or some 25 percent. The prognostic ability of ST2 was examined for both rejection and death. ST2 concentrations were measured approximately a month after transplantation and found to be highly predictive of short-, intermediate-, and longer-term outcomes.

“A monitoring strategy for the rejection that directly relates to its underlying pathophysiology would be an attractive choice,” notes the study authors. “Biomarkers reflective of rejection are an option . . . a novel biomarker candidate worthy of consideration for this application is ST2.”

Study: Interleukin receptor family member ST2 concentrations in patients following heart transplantation.

Source: Critical Diagnostics