Stem cells taken from people with an inherited type of dementia have been cultured in a lab with a hope of identifying possible new treatments, researchers in Belguim say.
Studying the stem cells with a mutation that predisposes people to development of frontotemporal dementia -- a form of the condition found in about half the dementia cases that develop before age 60 -- the researchers report identifying a defect that interferes with normal neurological development.
When the defect was targeted and corrected, the stem cells partially returned to normal, they said in the journal Stem Cell Reports.
Frontotemporal dementia, which can bring on behavioral symptoms or emotional and language disorders, is caused by damage to neurons in regions of the brain known as the frontal and temporal lobes.
Mutations in one gene known as progranulin (GRN) are often linked with frontotemporal dementia, but such GRN mutations have been difficult to study in usual animal lab experiments, since they do not display all the symptoms of the human version of the disorder, researchers say.
"Use of induced pluripotent stem cell (iPSC) technology makes it possible to model dementias that affect people later in life," says senior study author Catherine Verfaillie of KU Leuven.
The technology takes skin cells from patients and reprograms them into embryonic-like stem cells, which in turn can become specific cell types relevant to the study of a particular disease, she explains.
The researchers created iPSCs from skin cells taken from three patients who carry the GRN mutation, then turned those immature cells into specific mature cells called cortical neurons, which are the most affected type of cell seen in frontotemporal dementia.
A defect in the GRN-mutated stem cells affected a particular signaling pathway, known as the Wnt pathway, which is vital to neuronal development, but genetic correction restored the iPSCs cell's ability to mature into cortical neurons, the researcher found.
"Our findings suggest that signaling events required for neurodevelopment may also play major roles in neurodegeneration," says study co-author Philip Van Damme of the Leuven Research Institute for Neuroscience and Disease.
"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."
Further study of what goes on in GRN-mutated cells could help identify some precise molecular targets for possible drug treatments for dementia, the researchers note.
