Rakesh Sindhi has performed hundreds of pediatric organ transplants since arriving in Pittsburgh in 1998, extending the lives of children in desperate need of a chance at a full life.
But he’s been in the game long enough that he’s seeing what he would rather not: repeat customers. About 20 percent of pediatric transplant recipients will require a second transplant surgery within 20 years, with more than half of pediatric transplant patients facing that reality at some point in their lifetime.
Sindhi, director of pediatric transplantation research at the University of Pittsburgh, has made it his research priority to extend the life of transplanted organs in the hope that one is all a recipient will ever need.
Since launching a company with the first FDA-approved test to predict transplant rejection in pediatric recipients, Sindhi has explored emerging precision and machine learning tools, enabling him to develop a new platform for choosing the best anti-rejection drugs for an individual patient. He wants to give future transplant recipients the best opportunity to avoid re-transplantation later in life.
“There are only a handful of anti-rejection drugs to choose from,” he said. “All we can do is learn how to use them well. Predicting rejection is one thing. Predicting the right drug to use is a whole different ballgame, and that’s the approach we have taken.”
Now he is back with a new startup that recently licensed his growing portfolio of intellectual property. He has approached the FDA to address the approval pathway and is preparing to approach the Center for Medicare & Medicaid Services (CMS) to address reimbursement.
Building on the Starzl Legacy
Sindhi came to Pitt from India to follow in the footsteps of Thomas Starzl, the godfather of organ transplantation, who arrived at Pitt from the University of Colorado in 1981. In 1989, Starzl and his team published results of a trial of a new anti-rejection drug that demonstrated a quantum leap in efficacy over the status quo of the time, cyclosporine, and with fewer side effects.
His discoveries across the spectrum of organ transplantation, from organ procurement and preservation to tissue matching, and surgical transplant technology paved the way for expanding beyond an initial focus on liver transplants to heart, lung, pancreas, intestinal and kidney. On the strength of these discoveries, Pittsburgh became the pre-eminent transplant capital of the world.
Today, the bespoke Thomas E. Starzl Transplantation Institute is carrying his legacy forward by exploring the immunologic complexities of transplantation to improve clinical outcomes.
Sindhi’s research at the Starzl Institute has centered on exploring the use of new precision medicine tools that can pair each transplant patient with the anti-rejection drug most likely to protect their new organ.
“If we can nail down injury pathways with precision, that would be the best way to choose a drug that addresses the type of rejection,” he said. “The goal is to, on day one, be able to pick the right drug. If you pick the right one up front, one organ may last a lifetime.”
Ready to Launch
The platform that Sindhi’s new company, CellPlex Biosciences, is building upon looks at 6,000 curated genes in tissue samples left over from decades of transplants done at the UPMC Transplant Center.
“We examine injury pathways cell by cell across different tissue regions to determine the type of rejection and the dominant pathways involved. Linking pathways to the cells and sites of injury acts as a force multiplier, improving our ability to select the best-suited anti-rejection drug,” he said.
But screening for large number of genes and pathways is expensive. His lab is currently using AI tools to determine the smallest number of genes that are the most relevant for screening, which could reduce the time and cost for the healthcare system.
Commercialization Support from the Pitt Ecosystem
Sindhi said he has received reliable support for his commercialization activity from Senior Vice Chancellor for Health Sciences Anantha Shekhar, the Office of Innovation and Entrepreneurship, and the Conflict of Interest Office for its role in managing issues related to research integrity.
He said he maintains a close working relationship with Maria Vanegas, director of licensing for the Innovation Institute (part of the OIE), who has helped him develop his intellectual property portfolio, which he said includes roughly 25 filed patent applications to date.
Sindhi said he has witnessed a sea change in the resources and the energy behind commercialization at Pitt since his arrival.
“It used to be a much more risk-averse landscape. It really has become much more encouraging and supportive,” he said.
That extends to Conflict of Interest, which he said has been more proactive in engaging with innovators to help them understand what is possible around innovation commercialization. “They will give you a fair hearing and tell you what you can do and what you cannot do. It’s a very good environment,” he said.
He is also grateful for the intramural support outside of his NIH grants that have propelled his work, including support through the Department of Surgery, the Hillman Center for Pediatric Transplantation, the Pediatric Surgery Scientific Research funds, as well as from families that have been impacted by the care they have received and have given back financially.
With his company established, Sindhi said he recently had an informational meeting with the FDA to explain the platform and how it will rank the different types of organ rejection. He has begun seeking seed funding to conduct the validation studies necessary for FDA approval.
He is also collaborating with other major transplant centers around the country to explore the potential of integrating his company’s platform into the transplantation process itself by testing, then perfusing donated organs with anti-rejection drugs before transplant.