News in Science

Cells in a dish 'replicate schizophrenia'

Model brain Researchers have successfully grown human schizophrenia nerve cells, enabling them to test out new drugs and better understand the complex mechanisms underlying the disease.

The cells, grown in a Petri dish, offer researchers a new way to study neurons from people with schizophrenia, which until now had been limited to using post mortem brain samples.

The team, led by Professor Fred H Gage of The Salk Institute for Biological Studies in the United States, used skin biopsies taken from four severely schizophrenic patients. They induced skin fibroblast cells to turn into embryonic stem cells, and then made these develop into a mix of three different types of neuron.

In effect they have made a living two dimensional model of the neurons likely to exist in a schizophrenic brain. Their work is reported in this week's online edition of Nature.

Gage and his team have also devised an ingenious way to assess 'neural connectivity', measuring how many other nerve cells each neuron is connected to.

Significantly, the schizophrenic neurons in their Petri dish only had about half the usual number of connections. This low connectivity is also seen in post mortem brains from people with the disease.

Interestingly, they found that growing the nerve cells with loxapine, a drug sometimes used to treat schizophrenia, had a dramatic effect on the neural connectivity, increasing it to 80 per cent of normal levels.

Gage and his team then looked at the genes expressed in the schizophrenic neurons and found that amazingly almost 600 genes were being expressed to a greater or lesser extent than normal. About a quarter of these genes are already implicated in schizophrenia from post mortem and blood studies. Some of the other 450 genes are likely to be involved too.

Individualised treatments

Gage envisages that one of the future uses of his laboratory neurons may be to help patients discover what drug will be best for them. "Most psychiatric patients may try many drugs before they find one that works", he says. "This may circumvent that process by enabling individualised treatments with the best drug for them"

Professor Vaughan Carr, CEO of the Schizophrenia Research Institute in Australia welcomes the work. But he points out that it is early days yet, as the cells have come from only four patients.

"What we would hope to see as cells from more patients accumulate is a stronger signal as to which genes are the most important," says Carr. "This could become a very useful technology."