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NIH scientists try a new twist on using ‘personalized’ stem cells for studying dementia

Researchers will test out more than 100 genetic mutations linked to Alzheimer's disease and related dementias

In an article published in the journal Neuron, National Institutes of Health (NIH) researchers outlined their plans for the iPSC Neurodegenerative Disease Initiative (iNDI), a project designed to help scientists better understand how genetic mutations lead to the brain cell damage underlying Alzheimer’s disease and other dementias. It is among the first projects supported by NIH’s Center for Alzheimer’s and Related Dementias (CARD), which aims “to stimulate, accelerate, and support research that will lead to the development of improved treatments and preventions for these diseases.” 

Cluster of neurons derived from induced pluripotent stem cells.
Dementia in a dish 2.0

Above are three clusters of neurons derived from induced pluripotent stem cells (iPSCs). Researchers who are part of the NIH iPSC Neurodegenerative Disease Initiative plan a new approach to testing out genetic mutations linked to Alzheimer's disease and related dementias in cells like the ones pictured above. Courtesy of the Ward lab, NIH/NINDS

The project is led by the laboratories of Michael E. Ward, M.D., Ph.D., principal investigator at NIH’s National Institute of Neurological Disorders and Stroke (NINDS), and Mark Cookson, Ph.D., principal investigator at NIH’s National Institute on Aging, (NIA).

iNDI relies on induced pluripotent stem cells (iPSCs). Like most stem cells, iPSCs can be raised in petri dishes to become new brain cells. However, iPSCs are different from other stem cells in that they can be derived, or reborn, out of a person’s skin or blood. Scientists have found the cells appealing to work with because they create the ability to study a patient’s disorder in disease-relevant cell types.

The downside of this approach is that cells from one person are genetically different from the cells of another. This makes it hard for scientists to consistently evaluate the impact a disease-causing mutation has on brain cells, and hard to figure out how different mutations relate to each other biologically.

To address this issue, the iNDI researchers plan to create a new set of induced pluripotent stem cell lines. Each line will carry one disease-causing mutation but in the same genetic background as all the other lines. They plan to do this for more than 100 different mutations known to cause Alzheimer’s disease and related dementias, making it the largest iPSC genome-engineering project to date.

Other scientists will be able to obtain samples of each cell line and any accompanying data that may result from future experiments. Drs. Ward and Cookson hope this library will speed the development of promising treatments for millions of people who suffer from these devastating disorders.

Reference: Ramos, D.M., et al. Tackling neurodegenerative diseases with genomic engineering: A new stem cell initiative from the NIH. Neuron, April 7, 2021.