Mapping cells for better Parkinson's research
Parkinson's disease is a common disorder with no cure available yet. An EU-funded project has produced a genetic and chemical map of the neurons affected by the disease, to support new research into diagnosis and treatments.
© Marco Antonio Fdez. - fotolia.com
Caused by the death of neurons in the brain that make dopamine, a neurotransmitter necessary for the control of muscle movement, Parkinson’s disease makes muscles increasingly stiff and causes shaking.
Researchers do not know why dopamine-producing neurons are vulnerable . However, it particularly affects older people The disease is expected to place an increasing burden on health-care systems as the EU’s population ages.
The EU-funded DOPAMINET project has taken an important step towards helping researchers understand how the disease takes hold by mapping how dopamine-producing neurons – dopaminergic neurons – function.
The research team discovered which genes make a cell into a dopaminergic neuron, the mechanism that switches genes in these cells on or off, and how the neurons respond to different types of chemical signal to produce dopamine.
“This research will make it easier for researchers to identify new molecules that could be made into drugs to diagnose and treat the disease,” says project coordinator Stefano Gustincich of Italy’s Scuola Internazionale Superiore di Studi Avanzati (International School for Advanced Studies).
Although a cure for Parkinson’s disease is still far away, he says, the project’s results should make it easier for researchers to work towards treatments that give a better quality of life of sufferers and cut the high healthcare costs associated with the disease.
State of the art studies
DOPAMINET was able to identify the new genetic information much more quickly than traditional research by taking advantage of automated screening and computer modelling tools. By examining genetic material from mice, zebrafish and sea squirts using very fast automatic analysis, the team found the genes that the different species had in common in their dopaminergic neuron cells.
Using their custom-built technique for analysing small amounts of genetic material – microCAGE analysis – and further automated screening, they then identified how these genes are activated, which ultimately leads to the production of dopamine. At the same time, they used computer-based mapping to model the network of chemical reactions that take place when dopaminergic neurons make dopamine.
Once all this information was in place, the team had a model for dopaminergic neurons that could be valid for different species, including humans. They tested their models for accuracy and used them to look for clues to possible lines of research for Parkinson’s disease treatments.
Separate work used the project’s data to convert skin cells into stable dopaminergic cells, confirming that its results are accurate. As part of their research, the DOPAMINET team also discovered a new class of DNA that helps activated genes produce the proteins that neurons need to function.
Sharing the data
The fundamental research and data from the project is publicly available, says Gustincich, while the project’s partners are applying for new funding to develop their research further.
To ensure that their data helps Parkinson’s disease research move forward, the project shared its discoveries as widely as possible, holding seminars with other scientists, pharmaceutical companies and, in particular, Parkinson’s disease associations.
For the new generation of Parkinson’s researchers, the project held a summer school in July 2012 to train them on the latest relevant expertise from different fields such as biology and computer modelling.
Gustincich says: “We are basic researchers – when we find out that what we do has such a positive effect on others, it is very motivating. For patients, these seminars help them know that they are not alone with the disease – they have thousands of people helping them.”
After the project ended in July 2012, a spin-off company was created to provide researchers and pharmaceutical companies with molecules that deliver this new class of protein-producing DNA to cells. This spin-off aims to help researchers find cures for some genetic diseases and to further finance further work into Parkinson’s disease.