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The researchers employed iPSCs gathered from the skin cells of two people suffering from Parkinson’s disease to create young, disease-specific neurons, which were then transplanted into a rat model with the same condition. This rat model allowed the researchers to precisely identify the point of development at which the neurons derived from iPSCs need to be transplanted to mature into neurons that can combat the symptoms of the disease in the brain of the animal.

A crucial step forward in clinical trials for Parkinson’s disease in human patients was published in Stem Cells and Development on June 22, 2023. The research involves the utilization of autologous induced pluripotent stem cell-derived neurons.

“This paper reports important progress toward development of an autologous cell replacement therapy for Parkinson’s disease,” says senior author Jeanne Loring, PhD, professor emeritus and director of the Center for Regenerative Medicine at Scripps Research and co-founder of Aspen Neuroscience, Inc. “These results give us confidence that personalized therapy is feasible for Parkinson’s disease.

For over 10 years, researchers have been working on creating ways to use induced pluripotent stem cells (iPSCs) for the treatment of many illnesses caused by faulty or inadequate cells. Those with Parkinson’s disease lack the neurons in their brains that produce dopamine, a chemical messenger. This lack leads to a decrease in dopamine and the distinctive tremors and slow action associated with Parkinson’s. Sadly, there is currently no remedy for this condition, and minimal methods of managing the symptoms. Each year, approximately 90,000 individuals receive a Parkinson’s diagnosis, and 10 million people around the globe are living with this disease.

Clinical trials involving stem cells as a replacement for dopamine-producing neurons to treat Parkinson’s disease are already underway. Instead of using cells from the patient’s own body, these trials make use of unmatched cells from either the laboratory or a donor.

“When you transplant neurons derived from someone else’s cells, those cells will be rejected by the immune system, requiring the use of immunosuppressive drugs that are often not well tolerated” says Loring.

Mariah Lelos and her co-senior author Loring, from Cardiff University, shifted their focus to iPSCs extracted from patients in their recent undertaking. In the study, they sought to pinpoint the peak stage of development in which transplanting the precursor neurons would mend optimal results.

Upon closer examination, the researchers uncovered the reason why two stages of early-neuron progenitors could both be feasibly grafted into the brain, but only the earlier progenitors were actually effective in treating the symptoms of Parkinson’s disease – younger cells had a much greater ability to connect with other neurons.

Examining the cells of the neuronal precursor stages, the scientists discovered that many genes associated with neuronal differentiation were switched off in the younger cells and switched on in the older ones.

“At this earlier time point, the cells are poised to become neurons, and when they are put into the brain, they receive the signals to turn on those genes and finish their development. This allows them to make connections with the host,” explains Lelos. “If they’re farther along in development, they no longer respond to those initial developmental signals.”

“Knowledge of which genes are turned on in neuronal precursors that are in the optimal developmental state to treat Parkinson’s can help researchers screen cells before transplanting them into patients,” Loring adds. “The gene expression analysis should greatly improve the probability of successful transplants,” she says.

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