Stem Cells Mimic “Miracle Grow” in Damaged Hearts
FDA May Give “Green Light” to Houston Study

This year, Nelson Aguia is planning his 70th birthday celebration. Last year, he was planning his funeral.

“This will be the happiest birthday party in all of Brazil,” says Aguia, a native of Rio de Janeiro. “I have reason to celebrate, God knows!”

Only recently, Aguia lay in bed, waiting to die. Brought down by the effects of end-stage heart failure, he was unable to walk, talk or breathe without severe chest pain.

Doctors had tried all the conventional therapies – bypass surgery, angioplasty, medication – but nothing worked.

“I was told to prepare for one final, fatal heart attack,” says Aguia. “There was nothing left to do but wait for the inevitable. I started planning my funeral to spare my wife the burden.”

Then, Aguia’s daughter who is a pediatrician in Brazil, read a newspaper article about an experimental trial that she believed could provide her father with one last chance for recovery.

“I never accepted the fact that my father would die ... I always held out hope,” says Terezinha Aguia, who has been labeled a “guardian angel” by her father.

At his daughter’s urging, doctors at Pro-Cardiaco Hospital in Rio de Janeiro offered a fast-failing Aguia an opportunity to become the first of 21 patients enrolled in what is believed to be the largest cardiovascular stem cell study in the world.

Conducted collaboratively between Houston’s Texas Heart Institute and Pro-Cardiaco Hospital, Houston doctors have been making frequent trips to Brazil since December 2001, when the study began, to treat damaged human hearts with stem cells taken from the patients’ own bone marrow. When implanted in the heart, would these stem cells, doctors wondered, help strengthen damaged heart muscle?

A year later, they had their answer. Patients not only improved, but they wildly improved, surpassing all expectations.

The results are published in the May 13 issue of Circulation, the journal of the American Heart Association.

Bouncing Back in Brazil

Only two months after being implanted with stem cells, the hearts of the treated patients were pumping much more efficiently. Patients did well on treadmill tests and their angina, or chest pain, decreased. Subsequent months showed continued, steady improvement.

Nelson Aguia, for example, bounced back in a splendid show of resilience. Within six months of receiving stem cell therapy, the man who couldn’t get out of bed was walking three miles every day around Brazil’s largest soccer stadium, swimming laps, and working eight hours a day as a pharmaceutical sales representative – a job he gave up years ago. This month, he’s learning some popular new dance steps, designed to “wow” his party guests.

“I’m ready for anything. This treatment has given me life,” says a grateful Aguia.

Others enrolled in the trial tell similar stories. Take for example, the patient who effortlessly sprinted up eight flights of stairs when a power outage in his apartment building made the elevator inoperable – a move that set his doctors’ nerves on edge.

Another was ecstatic when he regained his sexual functioning. Once a week, he now “intimately visits” his wife.

“These people are reborn. The stem cell injections ‘woke up’ their hearts,” says Emerson Perin, M.D., Ph.D., director of New Interventional Cardiovascular Technology at the Texas Heart Institute. Perin, a native Brazilian who maintains close clinical and research ties with Pro-Cardiaco Hospital, performed the stem cell implantations in Brazil.

While the clinical team is optimistic about the patients’ dramatic improvement, doctors aren’t sure yet exactly how the stem cells do what they do, says James T. Willerson, M.D., senior author of the Circulation article and medical director and director of cardiology research at Texas Heart Institute.

“Either these stem cells became new blood vessel cells and new heart muscle cells, and/or their presence stimulated the development of one or both.”

Nelson Aguia doesn’t care why it works – only that it does.

“Getting my life back is good enough for me,” he says.

The Houston Connection

In the Brazilian study, 14 patients with an average age of 56 received the stem cell therapy, and were compared to another seven who served as a comparison, or “control group” that received no stem cells. Two patients died – one control patient and a treated patient who died 14 weeks into the trials.

The fact that only two deaths occurred in such desperately ill patients speaks volumes, says Perin, noting that without the stem cell therapy, the number of deaths would far exceed two.

“This is encouraging news for cardiac patients who have exhausted all treatment options and reached the end of the road. Now we have hope on the horizon.”

The Food and Drug Administration may soon agree. Currently, the agency is negotiating with Perin and other key Texas Heart Institute and St. Luke’s Episcopal Hospital players on the final details for a similar study to be held in Houston. If approved, the study could begin as soon as this summer.

While the primary focus of the Brazilian study was to demonstrate the technique’s safety, the Houston study’s goal is to prove its effectiveness. Already, 30 Houston patients have been selected to undergo the same type of stem cell implantation as their Brazilian counterparts.

The procedure is minimally invasive, and uses a catheter to carry harvested bone marrow stem cells straight to the heart. Under the right conditions, stem cells will potentially give rise to, or differentiate into, the cell types that make up the organism into which they are injected – in this case, the heart muscle.

“The goal of this treatment is to replace damaged heart muscle cells and promote the growth of new blood vessels that will supply oxygen to the damaged heart muscle. The stem cells are going ‘to the rescue’ to accomplish this,” explains Perin.

To conduct the procedure, doctors harvest stem cells from a patient’s bone marrow, isolate those cells most likely to develop into the cell type needed in the heart, culture them for three hours, then inject the candidate cells into the heart.

The cells are carried to the left ventricle, the main pumping chamber of the heart, through a small catheter that is inserted through a tiny incision in the patient’s groin and threaded upward through the body, into the heart. A needle then is sent traveling through the catheter until it emerges into the left ventricle, where the catheter ends.

Using a 3-D map of the heart shown on a video screen, doctors identify the areas of the heart that are suffering the most and target those specific areas for injection.

“We make sure the tip of the catheter is perfectly situated against the heart wall, then we inject the needle into the heart muscle, delivering millions of stem cells to that one little spot,” says Perin.

Injections are placed into the areas of the heart that are in greatest need of repair. In Nelson Aguia’s case, 11 sites were targeted within his heart.

To prevent infection, the entire procedure – from harvesting bone marrow to injecting stem cells – is done in one day.

“Take the cells out of the marrow, get them into the heart quickly – that’s the goal. The longer the cells are exposed, the greater the risk of infection,” explains Perin.

The therapy stems from Texas Heart Institute animal research conducted by Willerson and Yong J. Geng, M.D., Ph.D., director of the institute’s heart failure laboratory, in which stem cells from dog embryos were used to treat adult dogs with heart attacks. After two weeks of treatment, scar tissue which forms where heart muscle dies after a heart attack was reduced in the adult dogs by 30 percent.

Willerson and Perin praise the therapy because it is inexpensive, simple to perform, and poses no risk of rejection, since patients are donating their own cells.

“Patients usually go home the next day ... it’s elegantly simple,” Perin says.

The proposed Houston study, like the Brazilian study, will last one year.

“The money is there (the study is funded by St. Luke’s Episcopal Hospital), the protocols and people are in place, the lab is ready,” Perin says. “Thanks to the Brazilian study, the groundwork is already laid.”

Plans for the Houston study specify that 20 participants will receive stem cell injections, and 10 will not. Because the trial will be randomized, patients won’t know if they received the treatment.

“I’m sensitive about the 10 who get left out,” Perin says. “Six months into the study, I plan to offer the stem cells to them as well. Most of the benefits resulting from the treatment occur within six weeks of implantation, so by six months, we’ve got solid data. It’s not a problem to let the control group have the stem cells at that point.”

Patients’ progress will be evaluated at one, three, six and 12 months, using the most sophisticated imaging techniques available.

“We’re going to follow the hell out of these people,” Perin says.

A Whole New Ball Game

As the Houston trial prepares to move forward, Phase 2 of the Brazilian trial is gearing up at Pro-Cardiaco Hospital. In this second go-around involving 30 new Brazilian patients, doctors are extracting from participants’ bone marrow two types of cells (top secret, Perin says, can’t tell you which ones) that were identified in the first Brazilian study as more effective than others in repairing heart muscle.

“These cells are to the heart like ‘Miracle Grow’ is to plants,” Perin says.

If the Houston and Phase 2 Brazilian trials go well, the next step is to conduct additional trials at centers throughout the world using the “Miracle Grow turbo cells.”

“Then we can talk treatment. If these studies produce spectacular results, and we have every reason to believe they will, it’ll be a whole new ball game for patients with heart disease,” Perin says.

---

©2006 Texas Medical Center

---

E-Mail: tmcinfo@texmedctr.tmc.edu
URL: http://www.tmc.edu/tmcnews/06_01_03/page_01.html