A new $6.9 million grant from the California Institute for Regenerative Medicine (CIRM) will support preclinical development of an investigational cell therapy for the heart created by USC Stem Cell scientists. The treatment aims to achieve something that's never been done before - healing cardiac muscle after a severe heart attack.
Clinical trials to test safety and feasibility in humans are targeted to launch in late 2027, thanks to support from the Marcus Foundation. The resources from CIRM will underwrite the activities necessary to obtain the Food and Drug Administration's go-ahead to begin that clinical trial, with sites at USC and the University of Washington.
It's a blessing and a privilege to be selected for funding like this. Now, with CIRM's support, we can just focus on the science and medicine."
Chuck Murry, MD, PhD, principal investigator, head of USC Stem Cell and the Robert A. Day Professor of Medical Innovation, Keck School of Medicine of USC
The therapy is designed to benefit a population at high risk, people who have suffered major heart attacks that leave the organ so damaged that it no longer functions properly. This is compounded by the heart's extremely limited ability to regenerate tissue. One in four of these patients dies within a week, and half within a month. Survivors of the condition, which doctors call "myocardial infarction with cardiogenic shock," face serious challenges to their quality of life, including further heart problems, psychological distress, cognitive impairment and frailty.
Today's standard of care can only treat symptoms, using drugs and devices that stabilize the heart and augment its work circulating blood through the body. Murry's research addresses the root cause by aiming to actually regenerate the heart instead. The investigational treatment is designed to seed new cardiac muscle derived from stem cells.
Tests of the treatment will represent the first time that a cell therapy to regrow heart muscle has been delivered to patients with acute heart injury.
"With the current state of the art, we essentially slow the rate of decline," Murry said. "Physicians can add years of life - and some life to those years - but it isn't healing. We shouldn't accept that as the status quo. I think we can do something about it."
A bridge that leads to the clinic
CIRM-backed preclinical development encompasses rigorous testing, process development, manufacturing and clinical planning.
The research team will map out a precise series of steps that ensures the consistency and potency of the treatment. Partners at the USC/CHLA Cell Therapy Program, a facility aligned with current good manufacturing practices, will then refine the process with an eye toward quality, safety and scalability.
From there, stem cells are banked, with a subset developed into cardiac muscle then frozen. Those cells constitute the therapy that will later be thawed, washed and used in the clinical trial.
In parallel, a final set of animal experiments will confirm the treatment's safety and effectiveness, conducted respectively at a specialized laboratory and in-house at the Keck School of Medicine.
Targeting patient impact and access
The last preclinical step will be to select participants for the trial. For this, Murry is collaborating with Sanjeet Patel, MD, PhD, Vaughn Starnes, MD, and other senior cardiac surgeons from the Department of Surgery at USC's medical school. To identify patients who will most benefit, the team will deploy an artificial intelligence algorithm developed by Patel.
An additional consideration will be ensuring that people from underrepresented populations can take part in the trial.
"CIRM wants to make medicines that are accessible to patients regardless of the ZIP code they were born into," Murry said. "The way I see it, this therapy shouldn't be available only to people in wealthy neighborhoods."
The treatment will be "off the shelf" - with no need to customize it for individual patients. This means it can be manufactured at large scale, contributing to its potential reach.
"Heart failure is a disease of the masses, the No. 1 cause of death in the United States," Murry said. "If we want to move the needle, we need something that is scalable. Being off-the-shelf reduces cost, which makes it more accessible."
As a tradeoff, the version moving toward clinical testing will require the administration of drugs that quiet the immune response to avoid rejection. Ongoing investigations in Murry's lab focus on developing a future generation of universal cells that won't call for immunosuppression.
Cell therapy to repair the heart has been at the center of Murry's research mission for decades. The prospect of testing his treatment in patients is a major signpost in his quest.
"It feels like we're finally on the precipice of doing this," he said. "I alternate between being thrilled and a bit humbled by what we're attempting. We're going to learn enormous things from this, and I just hope we do well for patients."
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