Using a virus to reprogram cells in the brain could be a radical way to treat Parkinson’s disease.
People with Parkinson’s have difficulty controlling their movements due to the death of neurons that make dopamine, a brain signalling chemical. Transplants of fetal cells have shown promise for replacing these dead neurons in people with the disease, and a trial is currently under way.
But the transplant tissue comes from aborted pregnancies, meaning it is in short supply, and some people may find this ethically difficult. Recipients of these cells have to take immunosuppressant drugs too.
Ernest Arenas, at the Karolinska Institute in Stockholm, Sweden, and his team have found a new way to replace lost dopamine-making neurons. They injected a virus into the brains of mice whose dopamine neurons had been destroyed. This virus had been engineered to carry four genes for reprogramming astrocytes – the brain’s support cells – into dopamine neurons.
Five weeks later, the team saw improvements in how the mice moved. “They walked better and their gait showed less asymmetry than controls,” says Arenas. This is the first study to show that reprogramming cells in the living brain can lead to such improvements, he says.
The effect of the virus was localised to the specific area where the team injected them. They did not see astrocytes turn into dopamine neurons in any other areas of the brain, nor were there any signs of tumours or other unwanted effects.
The team has also used the same four genes to convert human astrocytes into dopamine neurons in a dish, suggesting that a technique like this may be possible in people. However, Arenas says careful safety checks and improvements to the technique are necessary before such a procedure could be tried in people.
“The critical question will be whether this would work in the aged human brain, and generate enough dopamine cells of the right type that can connect up with the brain in the same way that transplanted dopamine cells can,” says Roger Barker at the University of Cambridge, who is leading the fetal transplant trial.
Journal reference: Nature Biotechnology, DOI: 10.1038/nbt.3835