Frontotemporal degeneration (FTD) is a form of dementia that tends to occur at a relatively young age, generally between the ages of 45 and 65.
Although the disease is just as prevalent as Alzheimer’s in this age group, it manifests itself quite differently. While Alzheimer’s affects all brain regions, FTD only affects the cell processes in the frontal and temporal lobe.
FTD causes progressive degeneration in cortical nerve cells (nerve cells in the cerebral cortex), which can in turn cause significant cognitive impairment in the patient in a relatively short frame of time. Patients with FTD often experience behavioural changes and difficulties with language. Memory loss and forgetfulness, however, are not among FTD’s common initial symptoms.
FTD is an inherited disease. Among its most common causes are mutations in DNA, which decrease the production of progranulin, a growth factor for cortical nerve cells. Until now, the direct link between a deficiency in progranulin and cortical nerve cell death had yet to be verified.
In the study, Susanna Raitano (KU Leuven Stem Cell Institute), Philip Van Damme (VIB and Clinical and Experimental Neurology, University Hospitals Leuven) and Catherine Verfaillie (KU Leuven Stem Cell Institute) used induced pluripotent stem cells (iPSCs) to study the effect of progranulin deficiency on the development of cortical nerve cells.
iPSC is a technology developed in 2006 that makes it possible to reprogramme any adult human cell into any other human cell type with the help of embryonic stem cells.
The KU Leuven and VIB research team took skin cell samples from various FTD patients and reprogrammed those cells into cortical nerve cells, which were then examined in cell cultures. The team’s analysis shows that the reprogrammed cells indeed developed slower than normal due to the genetic mutation and the associated shortage of progranulin.
The team was also able to correct this mutation, which normalised cortical nerve cell growth.
The researchers also observed an overabundance of the signal molecule Wnt in the mutated nerve cells. When the Wnt signalling pathway was supressed, cortical nerve cell growth normalised as well.
Reprogramming the cells of patients with dementia can lead to new insights into the mechanisms at the basis of the disease, says Professor Catherine Verfaillie. “In this study, we looked at dementia caused by hereditary factors. But this technology also opens the possibility of studying disease profiles for which no specific genetic cause is known, something we are unable to do with animal models.”
Vlaams Instituut voor Biotechnologie (VIB)