'Disease in a Dish' Could Help Huntington's Patients

Researchers have discovered that working with pluripotent stem cells or iPS cells could help to establish "disease in a dish" to treat certain medical conditions, ranging from diabetes to Alzheimer's disease.

"A highlight of our model is that our progenitor cells and neurons developed cellular features of HD such as intranuclear inclusions of mutant Huntingtin protein, which most of the currently available cell models do not present," said lead study author Anthony Chan, PhD, DVM, associate professor of human genetics at Emory University School of Medicine and Yerkes National Primate Research Center, in a news release. "We could use these features as a readout for therapy using drugs or a genetic manipulation."

Researchers first worked to create a transgenic nonhuman primate model of Huntington's disease--a neurodegenartive disorder that affects muscle and cognitive function. The disease is typically caused by a mutation that introduces an expanded region where one amino acid (glutamine) is repeated dozens of times in the hungtingin protein.

Researchers used a non-human primate model with extra copies of the hungtington gene that contains the expanded glutamine repeats for their studies. However, in the non-human primate model, motor and cognitive deficits appear more quickly than in most cases of Huntington's disease in humans, which become noticeable within the first two years of the monkey's development.

They created a technique that uses retroviruses to introduce reprogramming factors into somatic cells and induce a fraction of them to become pluripotent stem cells-tissues that are able to differentiate into any type of cell in the body, with the right conditions.

The researchers used iPS-derived neural cells developed intracellular and intranuclear aggregates of the mutant hungtingtin protein--a classic sign of Hungtington's pathology, as well as increased sensitivity to oxidative stress.

"We tested two known experimental interventions, but our findings are a proof of principle that this system could be a valuable tool for the discovery and evaluation of other therapies," Chan concluded.

More information regarding the findings can be seen via the journal Stem Cell Reports.