ACTRI-Supported Cardiologist Adler Studies Novel Therapies for Rare Heart Disease

March 20, 2017 | Patti Wieser

Eric Adler, MD

Seven years ago, Eric Adler, MD, was at a hospital bedside, puzzling over a patient’s condition. The exploration took the physician-scientist back and forth between the bedside and the lab to analyze blood and tissue samples. Eventually, Adler diagnosed an extremely rare heart condition called Danon disease – one that affects perhaps one in a million. “We couldn’t figure out what the patient had for the longest time and even figuring it out there was no therapy,” said Adler, a cardiologist at UC San Diego.

Today, his journey continues. With support from UC San Diego Altman Clinical and Translational Research Institute (ACTRI), Adler is studying a novel treatment for Danon disease using gene replacement therapy in Danon mouse models. Adler received a 2016 ACTRI pilot project award and the 2016 Daniel T. O’Connor Memorial Award to supplement his pilot research. The project period concludes March 31.

“With the help of ACTRI, we’ve been able to fund and perform critical mouse experiments,” Adler said. “These are very patient-oriented studies to develop a potential new treatment for Danon disease that may have implication for a whole host of other diseases.” For example, a discovery could also be relevant to treating heart conditions resulting from some chemotherapies that affect cell function.

A mutation in the LAMP2 gene causes Danon disease, which is characterized by improperly functioning autophagy. Autophagy is a self-regulating process in which cells rid themselves of unneeded components. The effects of malfunction are heart disease, muscle weakness and learning issues. “Patients with Danon disease can’t perform autophagy well and they get premature heart disease and typically die in their 20s from heart failure, and there are no real therapies,” Adler said.

During the past seven years, Adler has expanded his Danon disease research from patient samples to stem cells to mice, and has seen the development of national and international collaborations strongly connected to Danon patients and groups. “We began by taking samples from a patient’s skin, turning those skin samples into stem cells to model the disease and then those stem cells into heart cells,” he said. To gain a better understanding of affected genes, Adler tested cell responses to a library of drugs and then moved into mouse studies.

Results from his ACTRI-supported study are coming in, and Adler anticipates publishing a paper within the next six months. He credits the success of the study to collaboration with Seaweed Canyon at UC San Diego for mice analysis, support from ACTRI and the O’Connor Award, and the bedside-to-bench-to-bedside circle—a circle in which the clinician-researcher flourishes.

“We’re inspired by what we see at the bedside and in the clinic and at the hospital to do the work that we do,” Adler said. “Having funding has galvanized our work.”

When the pilot project concludes, he plans to conduct more research on animals to test a promising therapy and consider early designs for a clinical trial with patients. “We want to understand mechanisms and we want to advance the science, but we really want to improve the lives of our patients,” Adler said.

Read the abstract of Dr. Adler’s 2016 ACTRI Pilot Project