Potential dementia treatment target identified using stem cell research

Researchers have identified a new treatment target for treating a common form of dementia after studying stem cells derived from patients.

Dementia treatment target identified using stem cell research

A stem cell model of a certain type of dementia has pointed to a new potential target for treatments, according to research published in Stem Cell Reports
on 31 December 2014. 

Stem cells with a mutation that causes frontotemporal dementia (FTD) are less able to develop into cortical neurons than stem cells without the mutation, it was found. Researchers used this model to identify processes inside the cell that are going wrong and that could be targeted by future treatments. 

FTD is the third leading cause of dementia in those aged under 65 years and yet there are no effective treatments for the condition, according to the Alzheimer’s Society.

This type of dementia has a strong genetic association — 40% of patients have a family history and their disease is usually linked to mutations in one of three genes.

Researchers at the Stem Cell Institute in Leuven, Belgium, took skin cells from patients with FTD who had mutations in a gene for progranulin, a protein that tells certain cells how to grow and develop.

Previous research into FTD using these types of stem cells looked at their ability to become a mixture of different types of neuron (brain cells). But this research looks specifically at the stem cells’ ability to become cortical neurons, the type of brain cell most affected in FTD. Development into cortical neurons decreased in the stem cells with the progranulin mutation and correcting the mutation — by inserting a healthy copy of the gene — reverses this effect.

Researchers also tried to identify how this mutation might be hindering cortical neuron development and they found that a signalling pathway called Wnt is very active compared to stem cells without the progranulin mutation. To confirm that the Wnt signalling pathway plays a role, the scientists inhibited Wnt and found that this allows the stem cells to develop into cortical neurons. The scientists now believe Wnt could be a therapeutic target in the future.

“Turning patient skin cells into brains cells in a dish holds tremendous promise for research into the condition as it allows us to unpick the complex biological pathways that go wrong in the brains of those affected,” says a spokeswoman for the Alzheimer’s Society. “As this research study shows, this can help researchers identify potential targets for the development of new drug treatments.”

The study’s authors believe the research supports the idea that the cellular and molecular defects in patients with this type of dementia may already be present in patients at a much younger age than when they develop the disease. “Causes of these diseases of aging may often already be present earlier in life and [this suggests] that additional events ultimately lead to the full manifestation of the symptoms of the disease,” say the authors.



[1] Raitano S, Ordovàs L, De Muynck L et al. Restoration of progranulin expression rescues cortical neuron generation in an induced pluripotent stem cell model of frontotemporal dementia. Stem Cell Reports 2014. doi:10.1016/j.stemcr.2014.12.001.

Last updated
The Pharmaceutical Journal, PJ, 17 January 2015, Vol 294, No 7845;294(7845):DOI:10.1211/PJ.2015.20067496

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