'Molecular microscope' system for transplant biopsy more effective than conventional methods

A transplant biopsy system that uses gene chips to read molecules is far safer and more effective than existing approaches used for heart transplant biopsies and is showing promising results for lung transplant biopsies, new University of Alberta-led research shows.

An international team of transplant specialists--including Philip Halloran, the founder of the "molecular microscope" system--presented early clinical trial findings of the system today at the 2018 meeting of the International Society for Heart and Lung Transplantation in Nice, France.

"Our research indicates that the molecular microscope system is more precise and accurate than conventional methods, which often involve extensive disagreement between doctors reading the biopsies, and therefore errors," said Halloran, a U of A transplant physician and globally recognized leader in the field.

The method uses gene chips (similar to computer chips) to read the molecules in heart and lung transplant biopsies. In the molecular microscope system developed by the U of A's Alberta Transplant Applied Genomics Centre (ATAGC) and investigators in North America, Europe and Australia, software converts the chip readings into diagnoses automatically.

Halloran said that the molecular microscope is a game changer in transplant medicine because it not only provides clinicians with insightful information for managing heart transplant rejection and treatment--which occurs in 150,000 patients worldwide every year--but also eliminates the confusion of unrecognized injury with rejection.

"Our findings suggest that, not infrequently, the current standard lacks the refinement to distinguish true rejection from other processes causing injury," said Daniel Kim, U of A transplant cardiologist. "This implies that, at times, patients could be treated for a condition they don't have. The molecular microscope's ability to more accurately diagnose rejection, before structural damage has occurred in a patient's heart, provides us with an essential tool in the evolution towards true precision medicine."

The molecular microscope system is now being developed for lung transplant biopsies, with the goal of changing care for those patients as well.

"Reading small lung transplant biopsies with a microscope is challenging--much more so than other transplantable organs--and that makes diagnosing rejection that much more difficult and prone to error," explained Kieran Halloran, assistant professor of medicine in the U of A's Faculty of Medicine & Dentistry. "This molecular diagnostic system is at an earlier stage in lung compared to heart and certainly to kidney, but is showing promising results that it can see similar information. That potential is very exciting for lung transplant clinicians."

He noted there is a huge unmet need for this type of precision medicine among lung transplant patients, who experience the shortest of all survival rates, often running into transplant trouble within five years.

"You can't hit what you can't see," added Philip Halloran. "Transplant rejection can be going on and we are missing it. And more commonly, rejection is way overdiagnosed, and patients are experiencing treatment complications for a condition they didn't have. Our system will change the approach to care."