The first human trial to demonstrate the efficacy of an implant-based treatment of this form of artificial pancreas starts
Fourteen years ago, during the heightened «stem cell wars» between scientists and the George W. Bush White House, there was a group of research advocates you could always count on to campaign: the parents of children with type 1 diabetes. Motivated by researchers who told them that these cells would result in incredible cures, they spent millions on television commercials, lobbying campaigns and countless congressional calls.
Now the first trial of a treatment for type 1 diabetes using stem cells has finally begun. In October last year, two bags of laboratory-cultivated pancreatic cells derived from human embryonic stem cells were inserted through an incision in the back of a San Diego man (USA). Since then, two other patients have received a substitute pancreas designed by a small San Diego company called ViaCyte.
It is also an important step because this trial of ViaCyte is only the third stem cell-based treatment to be tested in the United States. These cells, once extracted from human embryos in their early stages, can be grown in the laboratory and maintain their ability to become any type of cell or tissue in the body. Another trial, which has already been cancelled, treated several patients with spinal cord injuries (see Geron closes a pioneering stem cell research program), while trials to transplant laboratory grown retinal cells into the eyes of people who are going blind continue (see Retinal transplants from stem cells).
Patients with type 1 diabetes have to constantly monitor their blood glucose level by pricking their fingers, carefully measure when and what they eat, and routinely inject the insulin that their pancreas should make. Insulin triggers the removal of excess glucose from the blood to store it in fat and muscles. In the case of type 1 diabetics, the pancreas does not make it because its own immune system has attacked and destroyed pancreatic islets, the tiny groups of cells that contain beta cells that secrete insulin.
The routine is especially hard for children, but if they don’t manage their glucose properly, they may suffer neural, kidney, blindness, and lower life expectancy. But despite years of research, there’s still «nothing» to offer patients, explains University of California at San Diego (USA) physician Robert Henry, whose center is doing the surgeries for ViaCyte.
Henry exaggerates a little, but not too much. There is something called the Edmonton Protocol, a surgical technique first described in the New England Journal of Medicine in 2000 that uses islets collected from corpses. By transplanting them, doctors at the University of Alberta (Canada) ensured that the seven transplanted patients did not have to use insulin for a whole year.
However, the hopes placed in the Edmonton Protocol were quickly dashed. Only half of the patients treated have remained without long-term insulin use and the procedure, which forces patients to take potent immunosuppressive drugs throughout their lives and is still considered experimental in the United States, is not covered by health insurers. In addition, there are very few suitable pancreas donors.
The success of the Edmonton Protocol came just two years after the discovery of embryonic stem cells in 1998. Those seeking a cure for diabetes quickly set a new goal: to combine something like the Edmonton Protocol with laboratory cultured beta cell technology, whose supply is theoretically infinite.
«We already had proof of concept that a transplant restores beta function and insulin independence,» says the scientific director of the Juvenile Diabetes Research Foundation (JDRF), Richard Insel. The JDRF is a non-profit organization with 300,000 members. «So it was clear that if we had another renewable cell source, a lot of people would benefit.
That’s why JDRF fought against the restrictions threatened by the Bush White House, and why its members backed a popular initiative in California (USA) that created the California Institute of Regenerative Medicine, a state agency authorized to invest $3 billion (about 2.64 billion euros) in stem cell research. The California institute has given ViaCyte six grants worth $39 million (about 34 million euros), more than any other company, and JDRF has invested another $14 million (about 12 million euros) directly into the company.
Although conceptually the idea of cultivating replacement beta cells is simple, in practice it has proved more difficult to do than you might have imagined. «When I arrived at ViaCyte 12 years ago, stem cell replacement was so evident. We were all saying:»That’s the easy part, the fruit closest to the ground,» says Kevin D’ Amour, the company’s scientific director. «But the fruit has turned out to be a coconut, not an apple.»
One of the challenges has been to turn stem cells into authentic and functional pancreatic cells, especially beta cells that secrete insulin. As no recipe has been found to achieve this, ViaCyte’s current method is to grow immature pancreatic cells and wait for the body to do the work of transforming them into beta cells.
The second problem is how to mislead the patient’s immune system, which attacks any transplanted cells. ViaCyte’s solution is a plastic mesh capsule filled with about 40 million immature pancreatic cells grown in your San Diego lab. The objective of the capsule is to block the passage of the immune system’s killer T cells, which are too large to pass through the mesh, while allowing transplanted cells to receive nutrients from the blood flow and detect and respond to the blood sugar level.
Animal study data from animal studies provided by ViaCyte to the U. S. Drug Agency last year to be cleared for human trials show that cells produce insulin, glucagon (which is secreted in response to low blood sugar levels) and somatostatin, a growth hormone, and successfully regulate blood sugar levels, at least in mice.
Although the trial now underway is primarily to test the safety of the method, Henry suspects that his patients may be able to reduce the amount of insulin they need to inject. Henry explains that he has already recovered a bag of evidence from the first patient, whose identity has not been released, and that it appears to be working properly. No one is sure how long the implanted cells will survive, but it is known that patients would have to receive implants periodically.
There are at least two other groups that claim to have controlled diabetes in rodents and may begin to conduct their own trials in the near future. One of them is BetaLogics Venture, a subsidiary of pharmacy giant Johnson & Johnson, which last year reported that it had reversed diabetes in mice using what its patents describe as a yarn scaffold inside a polyester shell. Whatever the exact device, it contains what Johnson & Johnson researcher Alireza Rezania calls «phase 7″cells, which are not mature islets yet, but are not as immature as ViaCyte’s precursors.
Harvard University (USA) biologist Douglas Melton, who has two children with type 1 diabetes, is concerned that the ViaCyte system is not working. It believes that deposits of fibrosis, a scar-like tissue, will adhere to the capsules, depriving the cells they contain of oxygen and blocking their ability to detect sugar and release insulin. Melton also believes that immature cells may take up to three months to become fully functional cells. And many of them will not turn into beta cells but end up feeling another type of pancreatic cells.