Researchers think they’ve found a way to more permanently treat an incurable movement disorder, by transplanting reprogrammed neurons made from stem cells into patients’ brains.
Parkinson’s is a neurological disorder that affects roughly 10 million people globally. It’s not fatal, but it gets progressively more difficult to live with; over the course of 15 years or so, people living with the disease may go from having a slight tremor in their hand to being unable to walk. These symptoms are caused by the death of the brain cells that produce dopamine, a neurotransmitter associated with movement.
Scientists working in Japan published a study in Nature on August 30 that showed they could successfully create these dopamine-producing neurons in the lab, and transplant them into macaque monkeys with a disease similar to Parkinson’s. These monkeys showed better control of their movement without adverse side effects for the two years the experiment continued. The authors believe this work suggests the therapy is ready for human testing.
The team, led by Jun Takahashi, who studies stem cells at Kyoto University, took advantage of the fact that all of our cells contain the same DNA. The reason we have so many cell types is because different parts of our DNA are expressed in different cells. Eyes only express eye DNA, skin only expresses skin DNA, and so on. Normally, once undifferentiated cells, called stem cells, “decide” what kind of tissue they’re going to be, they stay that way for the rest of their lives.
However, chemical coaxing can force genetic changes on adult tissue cells that make them behave like stem cells. These are called induced pluripotent stem cells, or iPSCs, and with a bit more chemical prodding, they can grow into almost any other kind of cell.
Takahashi said that he and his team spent 17 years figuring out exactly the right cocktails needed to make dopamine-producing neurons from human iPSCs. For this experiment, they took skin or blood cells from four human donors who did not have Parkinson’s, and three who did. They converted these cells into iPSCs, and then into neurons which were transplanted into monkeys that had been given drugs that made them express symptoms of Parkinson’s disease. After the transplant, overall the monkeys’ movements were a lot more controlled, suggesting that the neurons made from stem cells had worked.
One concern the researchers had was that the monkeys’ immune cells would attack the stem cell transplants, forming tumors. In a separate paper published simultaneously in Nature Communications, the team showed that adding a group of the monkey’s own immunity proteins to the cell transplant helped suppress their natural immune response. “The grafted cells survived for two years in the brain without forming any tumors,” Takahashi says. This particular species of macaque lives to up to 30 years old, so these results are comparable to roughly six human years.
At the moment, one of the most common treatments for Parkinson’s disease are drugs that mimic dopamine. Unfortunately, because dopamine also plays a role in the brain’s reward cycle, these drugs often have horrible side effects—including compulsive gambling, shopping, and sex.
Takahashi says that he hopes that clinical trials for his stem cell therapy, for patients with a moderate form of Parkinson’s, can get underway by the end of 2018.
A previous version of this story incorrectly stated that the monkeys had been genetically modified to express symptoms of Parkinson’s. In fact, they were given drugs to accomplish this.