Delmar Chase, 74, has had two coronary bypass surgeries, stents inserted into his arteries to prop them open, and a pacemaker to keep his heart beating normally. Still, he gets chest pain when he walks even a block.
Relief may be on the way. Chase is enrolled in a Baxter International Inc. study, to be completed in 2009, testing if stem cells taken from his bone marrow can strengthen his heart. The trial is one of 50 involving 3,200 patients worldwide conducted by academic researchers and a dozen companies racing to market new treatments for heart disease, the No. 1 U.S. killer.
In March, Osiris Therapeutics Inc. and Mytogen Inc. showed in separate studies involving 60 patients that stem cells improved the pumping of diseased hearts. Two weeks ago, Baxter said a similar therapy decreased chest-pain in two dozen people, spurring a 4.5 percent stock rise. Further reports may help investors determine if these new therapies will crack the $33 billion-a-year U.S. cardiac-care market.
“There's a lot of money to chase and a lot of companies want a piece,'' says Jose Haresco, an analyst with Merriman Curhan Ford & Co. in San Francisco. “Cardiology is the largest area of health expenditures in the country, bigger than cancer.''
Most heart therapies prevent cardiovascular damage by lowering blood pressure or cholesterol. No existing treatment can actually reverse heart failure, a condition that weakens cardiac muscle and often follows a heart attack. More than 5 million Americans have the disorder, according to the American Heart Association.
Only Adult Cells Tested
The new experiments all use adult stem cells harvested from blood, bone, muscle and fat. Stem cells extracted from embryos may be more effective in rebuilding hearts, researchers have said. American trials use the less controversial adult cells because the U.S. government won't finance research that derives stem cells from embryos.
The human studies generated criticism from scientists who say it is premature to test stem cells in patients, and that much of the positive data is coming from company-sponsored trials.
Adult stem cells are gathered from a patient's own organs, purified and grown in the laboratory before being injected back into an individual's heart. In March, closely held Mytogen, based in Phoenix, reported that it used such a technique to treat 12 heart failure patients.
Six months after the cells were injected, the participants' hearts were pumping more efficiently, researchers reported at the American College of Cardiology's science meeting. New heart tissue that grew in scarred areas also had the electrical signature of viable cardiac muscle, said the report's author, Nabil Dib, director of clinical cardiovascular cell therapy at the University of California, San Diego.
Mytogen
In May, Advanced Cell Technology Inc., an embryonic stem cell company based in Alameda, California, agreed to acquire Mytogen for $5 million and to assume $1 million in debt. The acquisition is expected to close later this month, and Advanced Cell said it already has tentative commitments that will cover the $20 million to $25 million needed to finish the research.
Osiris, based in Baltimore, is developing a treatment technique that promises to be easier for hospitals to use. The company uses cells gathered from unrelated donors and injects them into a patient's vein.
Since as many as 5,000 treatments can be made from one donor, “the cells can be produced in quantity, in advance, offering the chance for an off-the-shelf product,'' said Marc Penn, director of the Bakken Heart-Brain Institute at the Cleveland Clinic.
Osiris
“It's an exciting concept, perhaps sea-changing,'' said Penn, who wasn't involved with the study.
The Osiris procedure reduced risks of irregular heartbeats in patients given the cells within 10 days of a heart attack, compared with patients on placebos, the study found. The company says it may begin larger trials next year.
Osiris's shares yesterday fell 38 cents, or 2.95 percent, to $12.50 in Nasdaq Stock Market composite trading. The stock rose as much as 25 percent on March 26 when the company presented its study.
Boston Scientific Corp., a Natick, Massachusetts-based heart-device maker, paid Osiris $5 million in 2003 for the right to market the therapy and agreed to provide an additional $25 million if the treatment wins approval from the FDA.
Critics say the human experiments are moving quicker than warranted. On June 29, Lancet, the U.K. medical journal, published a commentary by four cardiologists arguing that large- scale trials should be postponed until more is known about how best to administer the therapy.
Criticism
The doctors, led by Harald Arnesen, a professor at Oslo's Ullevaal University Hospital, noted that the most positive findings primarily come from company-sponsored research.
The idea that stem cells, the building blocks of all cells, will evolve into heart tissue and rebuild the heart is “a fascinating theory,'' Arnesen said in a telephone interview. “We just don't have the right protocol.''
Kenneth Chien, a Harvard University researcher, says human studies should be put on hold until scientists better understand how stem cells work. He also contends that the focus of research should shift to more adaptable embryonic cells. Last year, Chien published research identifying a single “master'' cardiac cell, derived from an embryonic cell, that turns into each of the three major cell types found in the heart.
He says scientists should carry out more studies in test tubes and animals before moving to people.
Questions
“What's the best way to deliver cells?'' Chien asks. “Injection into the heart, in the bloodstream, through catheters? Which cells? Bone marrow? Fat cells? Skeletal muscle myoblasts? We don't really know.''
Answering such questions is the point of early studies, said Stephen Minger, director of the stem cell biology laboratory at King's College in London. Adult stem cells may also serve as a useful bridge until researchers better understand how to work with embryo-derived cells, he said.
Minger thinks the bone marrow cells are helping form new blood vessels, which the damaged heart needs. The ultimate stem cell treatment may be a combination of adult cells to stimulate blood flow and embryo-derived cardiac cells to form new heart muscle, he said in an interview.
Advanced Cell hopes to use the experience it's now gaining with adult cells to move embryonic stem cells into human trials and onto the market, says CEO Caldwell.
First Piqued
“We are looking at adult stem cells as a first generation therapy to be followed by later generations which will be more powerful,'' Caldwell said.
Interest in the potential of adult stem cells to treat heart disease was first piqued in the mid-1990s after studies showed the cells could be coaxed into forming cardiac muscle cells that contracted rhythmically in a dish. In subsequent studies, stem cells delivered to damaged hearts in live animals appeared to reduce the amount of scar tissue.
In 1998, Doris Taylor, a researcher then at Duke University Medical Center in Durham, North Carolina, took myoblasts — a type of stem cell derived from muscle — from the legs of rabbits and transplanted them into their hearts after they'd had a heart attack.
New cells grew in damaged parts of the heart and its pumping ability improved. The stricken bunnies got better.
Delmar Chase says he hopes cells derived from his bone marrow will help strengthen his heart as well. Because researchers don't know if patients received stem cells or a placebo, Chase won't be told until at least 2009 if he was given the treatment.
`Great Faith'
Chase received the cells in February at the Scripps Institute's Green Hospital in La Jolla, California. “This is something we've been waiting for,'' Chase said in an interview just prior to undergoing the procedure. “I have great faith.''
During the operation, cardiologist Richard Schatz, a 54- year-old former Army surgeon, peered intently at six monitors that displayed graphic images of Chase's heart produced by a camera mounted on a catheter, a thin, hollow wire threaded into an artery running from his groin to his heart.
Guided by the images, Schatz and other doctors manipulated the catheter to areas of the heart getting too little blood and oxygen. Then, using a syringe on the catheter, they plunged a needle into the heart's wall and discharged either the stem cells or the saline solution.
Over two hours, the doctors repeated the process 10 times.
A New Use
For Baxter, a Deerfield, Illinois-based maker of drugs and medical equipment, the result could provide a new use for its $50,000 to $60,000 Isolex machine, originally produced to select the stem cells in bone marrow for cancer patients getting marrow transplants.
Baxter plans to treat the last of the 150 patients in the study by March next year, and will follow the patients for a year after that. Then, Baxter will decide whether to finance a larger trial that could be submitted to the FDA, says Andrea Hunt, the company's vice president for cellular therapies.
The company's shares rose $1.19 or 2.1 percent, to $58.09 yesterday in New York Stock Exchange composite trading. The stock has increased 58 percent in the past 12 months.
Chase believes the Baxter study is already a success, at least for him. He's needed only about one nitroglycerine tablet a week, mostly when he walks on the treadmill, since three weeks after the operation occurred. Before the trial, he was averaging four a day, he said. For that reason, he assumes he got stem cells, not saline.
“I'm pretty sure we're on the right road,'' Chase says. “It's the best news I've had in 35 years.''
