Dr. Ivar Mendez
Parkinson’s, is not a kind disease. As dopamine-generating cells in their brains deteriorate, patients must deal with tremors; their feet may suddenly seem to freeze to the floor; they may have difficulty swallowing. …
Parkinson’s, is not a kind disease. As dopamine-generating cells in their brains deteriorate, patients must deal with tremors; their feet may suddenly seem to freeze to the floor; they may have difficulty swallowing. Walking becomes a stiff-limbed shuffle.
While drugs such as levodopa and dopamine agonists have greatly enhanced quality of life for Parkinson’s patients, their effectiveness diminishes over time. Deep brain stimulation has also proved helpful, but it does not slow the pace of neurodegeneration.
Stem cell transplants, however, may offer a longer-lasting solution.
“I think Parkinson’s is going to be the first neurological condition where stem cell therapy will be used widely,” says Dr. Ivar Mendez, Unified Head of the Department of Surgery at the University of Saskatchewan. “We’re looking at transplanting one cell type. So we can direct the stem cells to become that type of cell — a Group A9 dopaminergic neuron.”
Transplanting cells into the brains of Parkinson’s patients in the hope of restoring dopamine neurotransmission is nothing new: it’s been going on for more than 25 years. The results, according to a 2013 report in The Lancet, “have been variable and, thus, the merits of this approach have been both questioned and championed.”
The variation in results has been attributed to, among other things, the use of different strategies or protocols for transplanting the cells. A key Canadian contribution to solving that problem is the Halifax Protocol for injecting cells into the human brain. Developed by Dr. Mendez, who was then at Dalhousie University, in collaboration with researchers from Toronto, Montreal and Calgary, the Halifax Protocol is regarded as the gold standard for effective brain repair using cell implantation.
“We developed the methodology for clinical transplantation,” says Dr. Mendez. “When reviewers looked at all the grafts of all the patients who have been transplanted across the world, it was felt that ours did the best, in large part because of the methodology we developed.”
Dr. Mendez is working with fellow Parkinson’s stem cell pioneer Dr. Ole Isacson of Harvard to use induced pluripotent stem cells created from skin tissue to make dopamine-generating cells that, once transplanted, will integrate into the brain circuitry and restore motor function.
The process is autologous, meaning the stem cells come from the patient themselves, so no immunosuppression therapy is required. As well, researchers have come up with ways to generate the millions of cells required and have developed processes to make those cells robust enough to do the job. So far, tests with large animals have shown positive results.
“We are continuing to work with animal models until we’re ready to start on a clinical trial, which should go ahead probably in the next two to three years,” says Dr. Mendez. “But I’m always concerned not to build unnecessary expectations among people affected by the disease.”
Other research centres are also working on a stem cell solution to Parkinson’s, with clinical trials using fetal cells currently underway in the United Kingdom.
“We’re very enthusiastic,” says Dr. Mendez. “Resolving the issue on a long-term basis, that is really the attraction. If one cell deteriorates or degenerates with time, can we actually replace that cell and reconstruct the circuitry? If we can, it’s a one-shot procedure. You do it only once and then the transplant will integrate into the host.”
Such a solution, however, could still be many years away. Researchers need to be sure the cells they inject will do the intended job, without causing additional problems or perhaps generating tumours.
“We’re quite advanced in terms of realistically looking at a clinical trial,” says Dr. Mendez. “But we have to make sure that the preclinical scientific evidence is solid to ensure success”
[Find out more about stem cells and Parkinson’s here.]