Researchers from the University of Copenhagen have developed stem cell models that can reveal the mechanisms behind the development of dementia – a common disease for which no treatment is currently available. The new stem cell models have revealed new imbalances in nerve cells. This paves the way for developing medication that can stop dementia before it manifests itself.

A team of researchers from the University of Copenhagen have now developed stem cell models that reveal imbalances in nerve cells, making it possible to develop medication to treat dementia.

“We have uncovered a number of the disease characteristics that are evident in the brains of people with Alzheimer’s disease and frontotemporal dementia. We have found clear imbalances in the nerve cells that end up killing the cells. If we develop medication targeted at restoring balance in the nerve cells, we can prevent them dying and thus treat dementia at a very early stage,” says Kristine Freude, Associate Professor at the Department of Veterinary Clinical and Animal Sciences.

The disease progression in dementia has long been a challenge to research in the area. The nerve cells in the brain cannot be studied closely enough while the patient is alive, and when the patient dies it is too late to look for the important early stages of these serious diseases. There has therefore been a great need to develop a stem cell model for patients’ brains, to make it possible to study how the disease develops. Using special stem cells, researchers have now succeeded in developing microbrains, which express the patients’ disease and can be studied at close hand.

When a person suffers from dementia, scientists generally cannot say why the disease has occurred. But in a few cases the disease is hereditary and can be seen in the form of a gene mutation. This mutation provides the basis for the researchers’ stem cell model.

“We have used the hereditary dementia case, which is due to a mutation, to study the disease characteristics that are generally seen in dementia. Put briefly, we compare nerve cells which have the mutation with healthy nerve cells. The places the mutated nerve cells are different from the healthy cells are the places we can target with new drugs to treat dementia,” says Kristine Freude.

The process starts with the researchers taking a tissue sample from a dementia patient with the mutated gene. They then use a special technique to convert the tissue samples into special stem cells – ‘induced pluripotent stem cells’ (iPS cells). These are a type of stem cell which has the ability to develop into any cell type in the body, including nerve cells. The mutation that causes the disease is then corrected in some of the iPS cells, making them ‘healthy’. Researchers make nerve cells from both the mutated and the healthy iPS cells.

The researchers then have two kinds of nerve cells – some with the mutation, and other healthy cells. Apart from the mutation, the cells are completely identical. The researchers can therefore be quite confident that the characteristics unique to the mutated nerve cells are related to the development of dementia, and are possible targets for treatment of the disease.

The researchers are the first in Denmark to use this special stem cell technique to develop dementia in a petri dish, raising Denmark to an international standard in this area.

The study, "Patient iPSC–Derived Neurons for Disease Modeling of Frontotemporal Dementia with Mutation in CHMP2B," was published in the journal Stem Cell Reports.