Induced Pluripotent Stem Cell Therapy in a Primate Model of Parkinson's Disease
Cell therapy continues to be a promising approach to establishing a treatment for Parkinson's disease. The intent is to replace the dopamine-generating neurons that are lost as the condition progresses. Researchers here report on the past few years of a cell transplant study carried out in monkeys made to exhibit the same cell loss that is produced by Parkinson's in humans. Unlike earlier efforts, the researchers here are using induced pluripotent stem cells in order to generate the neurons to be transplanted.
One of the last steps before treating patients with an experimental cell therapy for the brain is confirmation that the therapy works in monkeys. Researchers have now shown that monkeys with Parkinson's disease symptoms show significant improvement over two years after being transplanted neurons prepared from human induced pluripotent stem cells (iPS cells). The study is expected to be a final step before the first iPS cell-based therapy for a neurodegenerative disease.
Parkinson's disease degenerates a specific type of cells in the brain known as dopaminergic (DA) neurons. It has been reported that when symptoms are first detected, a patient will have already lost more than half of his or her DA neurons. Several studies have shown the transplantation of DA neurons made from fetal cells can mitigate the disease. The use of fetal tissues is controversial, however. On the other hand, iPS cells can be made from blood or skin, which is why researchers plan to use DA neurons made from iPS cells to treat patients.
To test the safety and effectiveness of DA neurons made from human iPS cells, researchers transplanted the cells into the brains of monkeys. It is generally assumed that the outcome of a cell therapy will depend on the number of transplanted cells that survived, but the researchers found this was not the case. More important than the number of cells was the quality of the cells. "Each animal received cells prepared from a different iPS cell donor. We found the quality of donor cells had a large effect on the DA neuron survival." To understand why, he looked for genes that showed different expression levels, finding 11 genes that could mark the quality of the progenitors. One of those genes was Dlk1. "We are investigating Dlk1 to evaluate the quality of the cells for clinical applications."
Another feature of the study that is expected to extend to clinical study is the method used to evaluate cell survival in the host brains. The study demonstrated that magnetic resonance imaging (MRI) and position electron tomography (PET) are options for evaluating the patient post surgery. The group is hopeful that it can begin recruiting patients for this iPS cell-based therapy before the end of next year.
Link: http://www.cira.kyoto-u.ac.jp/e/pressrelease/news/170831-090000.html
We need to develop some form of cell therapy that doesn't involve surgery, even more so in the case of brain surgery and old patients, like those with PD. But anyway this is an important step forward.