New study will examine use of gene modified stem cells to aid Dobermans with heart condition

Expanding earlier research, University of Florida College of Veterinary Medicine cardiologists have begun a pilot study using adult stem cells to repair heart function in Doberman pinschers with a common heart condition.

Researchers hope to build on their results to further explore the technique in other breeds of dogs.

"Our goal would be to try to regenerate and bring new muscle cells into the heart," said Amara Estrada, D.V.M., an associate professor and chief of the UF Veterinary Medical Center's cardiology service.

The Doberman Pinscher Club of America has provided $72,000 for Estrada's team to study up to 15 dogs with early stage dilated cardiomyopathy, known as DCM. A common disease of the heart muscle, DCM affects both dogs and people. Although people may benefit from aggressive therapy, such as heart transplants or ventricular-assist devices, medical therapy is the only current treatment option for dogs afflicted with the disease. At best, however, such treatment only prolongs the inevitable.

"When a person gets this disease and their heart fails, they typically go on a list to receive a transplant," Estrada said. "But when our patients get it, they are done."

Procedures such as open heart surgery or ventricular assist devices would be cost-prohibitive for most animal owners, Estrada said.

"If this technique works, it would provide an affordable treatment option and one which never existed before," she said. "People wouldn't have to watch their dogs suffer."

Dobermans are afflicted with DCM more frequently than any other dog breed, and experience extremely high mortality rates. Most Dobermans with this condition die within six months. "Other breeds of dogs with this condition do not have as rapid a course, but do eventually succumb due to refractory heart failure," Estrada said.

Judith Brown from the Doberman Pinscher Club said she heard Estrada's name mentioned by another researcher with an interest in DCM. Brown contacted Estrada right away.

"This disease is an enormous problem in our breed," she said. "We are all losing dogs because of it. We have been looking for some time for a viable study to donate funds, and which we could really believe in," Brown said. "I feel like if you are going to donate to anything, you might as well make a difference."

Brown said she had spoken to a lot of investigators, but was immediately impressed with Estrada.

"Our dogs are dropping dead in front of our faces," Brown said. "Dr. Estrada had the empathy and understanding of what we're dealing with. A lot of people don't seem to get it, but she did."

Preliminary data from Estrada's study will be used to apply for larger-scale clinical trials for Dobermans with DCM, and also for possible exploration as a translational model for additional studies of the disease in people, Estrada said. Over the past one and a half years, Estrada and her colleagues at the Powell Gene Therapy Center at UF have removed stem cells from rats and mice, modified them, and returned them to the animals to repair damaged heart tissue.

"The major advantage of this cell type is their ability to avoid the immune system, therefore allowing them to engraft in the heart and survive without rejection," Estrada said.

Transplantation of these stem cells has emerged as a safe and effective means to repair left ventricular pump function in experimental animal and human patients, researchers said. The cells are cultured and maintained in the laboratories of Barry Byrne, M.D., Ph.D. and Thomas Conlon, Ph.D., at the Powell Gene Therapy Center.

"This technique follows the latest trend in gene therapy with combination of stem cells as a platform for expressing therapeutic proteins," Conlon said. "We are really encouraged by the previous studies and excited to be a part of Dr. Estrada's research as not only a potential treatment in canines, but it could be potentially therapeutic in people too."

Dogs participating in the study will be anesthetized and cells will be injected via catheter into the coronary sinus — essentially a channel through which blood flows into the heart. Follow-up examinations will take place at one month, six months, 12 months and 18 months.

To identify registered Dobermans appropriate for the study, Estrada will be arranging several screening clinics at dog shows and other venues during the next few months. To meet the criteria, dogs must be asymptomatic but will show evidence of cardiac dysfunction as the result of various screening tests.

For more information, contact Estrada via email at estradaa@vetmed.ufl.edu or through UF's small animal hospital at 352-392-2235.