Parkinson Disease Cells Show Poor Ability to Form Nerve Extensions in Lab Setting

Nerve cells developed from the stem cells of people with Parkinson disease had significantly less ability to form the extensions necessary to create connections and transfer dopamine from one nerve cell to another compared with cells developed from healthy control subjects, according to a study published in the journal Cell Reports.

“We work with nerve cells in a petri dish, and we do not know if the same thing happens in a brain,” explained first author Helle Bogetofte Barnkob, MD, PhD, of the University of Southern Denmark and Oxford University. “But we can say that nerve cells developed from Parkinson disease patients’ stem cells cannot form extensions as well as those from healthy patients.”

Investigators tapped a large bank of stem cells from people with and without Parkinson disease at the Oxford Parkinson’s Disease Center in the United Kingdom. The study also relied on advanced, proteome-analyzing equipment at the University of Southern Denmark in Odense, which can provide insight into thousands of proteins and protein modifications simultaneously.

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When researchers investigated whether they could treat the lab-developed Parkinson disease nerve cells, they found the cells responded to a substance used to treat the rare Gaucher disease. By boosting the so-called GBA enzyme, the substance enabled the Parkinson disease cells to better form nerve extensions, the research team reported.

The stem cells used in the study came from Parkinson disease patients with a mutation in the GBA gene, the most common genetic risk factor for the illness. However, up to 90% of cases of Parkinson disease are not believed to be genetically determined alone but are rather sporadic and caused by a mix of genetic and environmental factors.

As such, Dr Barnkob is currently investigating nerve cells formed from the stem cells of patients with sporadic Parkinson disease to see whether the disease mechanisms behind sporadic and genetically determined Parkinson disease are similar.

References

Bogetofte H, Ryan BJ, Jensen P, et al. Post-translational proteomics platform identifies neurite outgrowth impairments in Parkinson's disease GBA-N370S dopamine neurons. Cell Rep. 2023;42(3):112180. doi:10.1016/j.celrep.2023.112180

New insight into dying cells in Parkinson's disease. News release. University of Southern Denmark; April 25, 2023. Accessed May 12, 2023.