A man in his mid-50s with Parkinson’s disease had fetal brain cells injected into his brain. He is the first person in nearly 20 years to be treated this way – and could recover full control of his movements in roughly five years.
“It seemed to go fine,” says Roger Barker of the University of Cambridge, who is leading the international team that is reviving the procedure.
The treatment was pioneered 28 years ago in Sweden, but two trials in the US reported no significant benefit within the first two years following the injections, and the procedure was abandoned in favor of deep brain stimulation treatments.
What these trials overlooked is that it takes several years for fetal cells to “bed in” and connect properly to the recipient’s brain. Many Swedish and North American recipients improved dramatically, around three years or more after the implants – long after the trials had finished. “In the best cases, patients who had the treatment pretty much went back to normal,” says Barker.
After the fetal cells were wired up properly in their brains, they started producing the brain signalling chemical dopamine – low levels of this cause the classic Parkinson’s symptom of uncontrolled movements. In fact, the cells produced so much dopamine that many patients could stop taking their Parkinson’s drugs. “The prospect of not having to take medications for Parkinson’s is fantastic,” says James Beck of the Parkinson’s Disease Foundation in the US.
Because the early trials missed this improvement no one had received fetal brain cells since the 1990s. But the man treated at Addenbrooke’s Hospital in Cambridge on May 18th did not receive a full treatment, because the team only had enough cells to treat one half of his brain.
The transplant depends on fetal cell donations from women terminating pregnancies, so the researchers don’t know when cells are likely to be available. It takes cells from at least three fetuses to treat each half of the brain, and four earlier attempts to treat the same man had to be stopped due to a lack of cells.
But Barker hopes to treat the other half of the man’s brain soon. “We would expect that if we do both sides, he will see an improvement in around six months to a year,” says Barker. But the maximum benefits are predicted to happen in three to five years’ time, and should then be sustained for more than a decade, he says.
The team plans to test the treatment in a further 19 people, in a trial split between Cambridge and Sweden.
Barker sees the revival of the technique as a stepping stone to injecting dopamine-producing cells made by stem cells. Trials of such treatments are expected as early as 2017, and Barker hopes lessons learned from the fetal cell transplants will guide how to apply and assess them once they are ready.
“We are now on the road towards a 2.0 version of the cell therapy paradigm,” says Lorenz Studer of the Memorial Sloan Kettering Cancer Center in New York. He thinks future treatment will eventually involve the use of dopamine neurons that come from stem cells rather than fetal cells, which will permanently resolve the supply problem.
Members of the Parkinson’s Disease Global Force met in New York last month to discuss the progress of this stem cell work. When Barker announced that his team’s first patient had just left the operating theatre, the meeting’s attendees burst into spontaneous applause.
“There’s a real sense within the community that this is a collaborative effort to make cell treatments work, and that there’s real potential to change the lives of hundreds of people worldwide,” said Barker.
The team behind the fetal cell treatment hopes it will pave the way for specific, custom stem cell treatments to replace the missing dopamine in people with Parkinson’s disease. Rather than relying on fetal cells, these stem cell treatments could in theory be made to order.
Four teams – two in Europe and two in the US – have managed to make neurons from embryonic stem cells and all are hoping to use them to treat people with Parkinson’s. Unlike fetal cells, these stem cells can provide a limitless supply of neurons because they can divide many times.
Meanwhile in Japan, researchers are using “induced pluripotent” stem cells to make dopamine-producing cells. Unlike embryonic stem cells, such iPS cells can be created from an adult’s ordinary body tissues.
Roger Barker of the University of Cambridge says all these teams are now gearing up to test their cells in patients, hoping to begin in 2017.