Fresh hope for dementia patients
Cells used to study "dementia in a dish" have led scientists to a potential new treatment strategy for an inherited form of the brain disease.
Defective stem cells grown in the lab revealed a signalling pathway linked to frontotemporal dementia (FTD), which accounts for about half of dementia cases before the age of 60.
Treatment with a drug that suppressed the pathway, known as "Wnt", restored the ability of neurons affected by the disease to develop normally.
Professor Philip Van Damme, from the Leuven Research Institute for Neuroscience and Disease in Belgium, said: "Our findings suggest that signaling events required for neurodevelopment may also play major roles in neurodegeneration.
"Targeting such pathways, as for instance the Wnt pathway presented in this study, may result in the creation of novel therapeutic approaches for frontotemporal dementia."
Mutations in the progranulin (GRN) gene are commonly associated with FTD, which results in damage to the frontal and temporal lobes of the brain.
The fact that GRN mutations produced in mice do not display all the features of the human disorder has limited progress towards effective treatments for FTD.
Instead of relying on animal tests, the new research involved creating human cells in a laboratory dish.
The scientists reprogrammed skin cells from three dementia patients into induced pluripotent stem cells (iPSCs), immature cells that mimic stem cells taken from early-stage embryos.
Like embryonic stem cells, they have the potential to become any kind of body tissue.
Each of the patients taking part in the study had a GRN mutation.
The aim was to recreate damaged neurons in the laboratory.
But the researchers found that iPSCs derived from the patients' were unable to generate cortical neurons, the cell type most affected by FTD.
Cortical neurons are the cells responsible for most of the brain's complex higher activity enabling thought, perception and voluntary movement.
The findings, reported in the journal Stem Cell Reports, indicated that defective GRN altered the Wnt signalling pathway which plays an important role in neuronal development.
Inhibiting Wnt either with genetic correction or a drug compound restored the ability of the stem cells to convert into cortical neurons.
Co-author Dr Catherine Verfaillie, from the University of Leuven in Belgium, said: "IPSC models can now be used to better understand dementia, and in particular frontotemporal dementia, and might lead to the development of drugs that can curtail or slow down the degeneration of cortical neurons."
In their paper, the scientists suggested that the underlying causes of dementia "may often already be present earlier during life".
They add: "Signalling events required for neurodevelopment may also play major roles in neurodegeneration and ... targeting such pathways - as for instance, the WNT pathway presented in this study - may result in the creation of novel therapeutic approaches for FTD."