Australian researchers have begun injecting insulin-producing cells taken from healthy pigs into people with type 1 diabetes in an attempt to cure their condition.
Crucially, the scientists claim to have all but eliminated the risk of infection from the animal transplants. Transplanted cells are encased in a porous gel that protects them from attack by the host immune system, doing away with the need for harmful immuno-supressive medication.
The trials follow preliminary tests in which two volunteers with type 1 diabetes, an autoimmune disease that results in the destruction of the insulin-producing islet cells in the pancreas. Insulin is vital for controlling blood-sugar levels, and patients with the disease currently face life-long insulin injections to prevent life-threatening surges in blood-glucose levels. The volunteers demonstrated independence from insulin shots for several months when treated by the technique, according to project leader Robert Elliott, cofounder and medical director of Living Cell Technologies. Preliminary tests were also done on primates, who suffered no side effects from the treatment.
“In the preliminary tests we showed that there is a clear benefit and a vanishingly small risk,” Elliot says. “So we have demonstrated what we need to go ahead with this large clinical trial.” The preliminary results were reported at the annual meeting of the International Society for Cell Therapy in May this year.
The radical technique will now be tested on 18 volunteers in a larger clinical study that will take place in Russia and New Zealand, because a moratorium on xenotransplantation exists in Australia–although that is up for review later this year.
Volunteers in New Zealand began receiving the encapsulated porcine cells in their abdomens this week in a “simple procedure” done under local anesthetic, Elliot says. All the volunteers have type 1 diabetes.
The Australian researchers are deliberately including in the trial some patients with unstable diabetes, whose condition is poorly controlled by insulin treatment. After an initial two-month evaluation period, the volunteers will continue to be monitored for months or years. If the transplants are successful, the researchers hope to be able to wean the subjects off insulin injections.
A lack of human donors has long pointed to the need for animal pancreatic tissue in such transplants. But earlier studies using xenotransplants to treat diabetes failed to show clear benefits. And none used the encapsulation technique, which spares clusters of transplanted pig cells, which are the size of grains of sand, from the ravages of the host immune system.
“This is the main thing, “Elliot says, “protecting the transplanted cells from this double whammy that comes from rejection of foreign tissue and the diabetes itself, in which the body attacks its own pancreatic tissue.”
Elliot says that the pigs used for the transplants were bred and kept in an exceptionally sterile environment, which meant they were “free of viruses, bacteria, and parasites.”
In addition, he says tests have shown that retroviruses hidden away in the pigs’ genes are not capable of producing viable viral particles. The discovery of such viruses in pigs in the late 1990s has been a key factor holding back xenotransplantation.
Anthony d’Apice, director of the Immunology Research Centre of St Vincent’s Hospital Melbourne, says demonstrating a good risk-to-benefit ratio will decide whether the trial is successful. “It’s about minimizing the risk of failure–and the risk of infection, which is not just a risk for the patients but also their contacts and the community, and this may be from known or unknown organisms including porcine endogenous retroviruses.”
Jonathan Stoye, a virologist at the U.K.’s National Institute of Medical Research and an advisor to the British government on xenotransplant safety, backs the study. “The risk from these porcine viruses is probably much lower than we feared at first–although you can never completely discount it,” he says. “I would like to see the clinical data before I draw any conclusions, but it seems to me to be a very good trial to be doing.”