Researchers in Oxford have begun creating a bank of artificially grown brain cells from Parkinson’s patients, BBC news has learned.
They are using a new stem cell technique that allows them to turn a small piece of skin from the patient into a small piece of brain.
This is the first time this has been done in a large-scale study aimed at finding cures for the disease.
Researchers say they can analyse nerve cells as they start to deteriorate.
The first batch of nerve cells have been grown from a 56-year-old Oxfordshire man, Derek Underwood.
He had to take early retirement because of the progression of the disease.
Mr Underwood will be the first of 50 patients whose skin cells will be grown into brain cells as part of a five year study.
Brain cells
According Dr Richard Wade Martins of Oxford University, who is leading the study, the aim is to build up a “brain bank” which will enable researchers to study how the disease develops in unprecedented detail.
“The brain is an inaccessible organ and you can’t get bits of people’s brain to study very easily,” he said.
“But what we have here is a disease in a dish, that are just like Derek’s brain cells but are accessible and can be produced in unlimited quantities”
The first step, according to Dr Michelle Hu of the John Radcliffe Hospital in Oxford, is to compare the brain cells grown from Parkinson’s patients, with those grown from healthy volunteers and see how they differ.
“For the first time we can look at the cells before they deteriorate and look at the earliest changes,” she said.
“We can look at what cellular processes are happening that make the cells die and learn why it is that the cells get sick. And we want to see if there are any treatments we can offer to reverse that process and help patients regain normal function.”
This is the first large scale clinical study to use a technique which was developed by Japanese scientists three years ago, called “induced pluripotent stem cell” or IPS for short.
Genes are inserted into the skin cells, reprogramming them to become something else.
IPS is similar to the embryonic stem cell technique which was used to create Dolly the Sheep, but IPS does not result in the creation of an embryo and so is regarded by some as an ethically more acceptable approach.
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A Californian team say they have managed to convert human skin cells directly into functioning brain cells.
The scientists manipulated the process by which DNA is transcribed within foetal skin cells to create cells which behaved like neurons.
The technique had previously been demonstrated in mice, says the report in Nature.
It could be used for neurological research, and might conceivably be used to create brain cells for transplant.
The scientists used genetically modified viruses to introduce four different “transcription factors” into foetal skin cells. These transcription factors play a role in the “reading” of DNA and the encoding of proteins within the cell.
They found the introduction of these four transcription factors had the effect of switching a small portion of the skin cells into cells which functioned like neurons.
Unlike other approaches, the process did not involve the reprogramming of the skin cells into stem cells, but rather the direct transformation of skin cells into neurons.
Marius Wernig, an assistant professor of pathology at Stanford University School of Medicine in California, was one of the researchers.
“We showed that it is possible to convert human skins cells directly into nerve cells which look and behave like nerve cells which usually only exist in the brain,” he told BBC News.
“It was known that it was possible to change a specialised cell back into a stem cell, what’s called an induced pluripotent stem cell (iPS), but it was not known whether a specialised cell could be pushed into another direction, other than backwards.”
Professor Wernig conceded that there were examples, some dating back many years, where specialised cells have been switched into similar cell types, but he believes this is the first example of where cells have undergone such radical conversion.
He believes the immediate application will be in modelling diseases, whereby skin cells from a patient with a known neurological condition could be used to produce new brain cells for research.
“It is very very difficult to look into the brain. There is a big skull which protects the brain very well and therefore it’s difficult to image,” he said.
“Everything that can be done at a cellular level is only possible after a patient has died, by which time the disease is usually in the final stages and you have no chance of seeing how the disease develops.”
The technique might one day also be used to create new brain cells which could be transplanted into patients with neurological disorders, he said.
Created from the patient’s own skin, these cells would be an exact match for the patient, although there would be many obstacles to overcome, not least the challenge of producing enough of the right type of brain cells.
Commenting on the study, Jim Huettner, an associate professor at Washington University School of Medicine, said the research was “convincing and important”.
“They have shown similar things in mice before but in humans they’ve discovered some subtle differences which often turn up when moving from mice to humans,” he said.
“But the work solidifies the idea that this kind of transition is possible and that it’s not just some fluke in the mice model.”