A breakthrough in understanding 
age-related disease

Researchers at IBEC have made an important leap towards understanding the second most common neurodegenerative illness, Parkinson’s disease (PD), which affects around 5% of the population by age 85.

Previously, it wasn’t clear whether induced pluripotent stem cells (iPSCs) – adult cells genetically reprogrammed to an embryonic stem cell-like state, which offer an unrivalled opportunity to understand many human diseases – were able to shed any light on illnesses which are age-related.

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However, in monitoring iPSCs from patients with two types of Parkinson’s alongside a healthy control group, the researchers witnessed the changes in the dopaminergic neurons that are necessary for the onset of the disease — and pinpointed the trigger for these changes.

“Parkinson’s, which can be either genetic or sporadic, is caused by a selective loss of these particular neurons in the part of the brain responsible for controlling movement,” explains Ángel Raya, who leads the Control of Stem Cell Potency group at IBEC. “We mimicked the ageing process outside the body by culturing three types of iPSCs – those from genetic PD patients, sporadic PD patients and a healthy control group – over a period of more than two months. We saw that the ones from both types of PD patients exhibited the changes in dopaminergic neurons necessary to the development of the disease, but not the ones from the healthy patients.”

This reveals that susceptibility to sporadic (non-hereditary) PD should be coded in patients’ genomes just as clearly as other patients’ tendency to the hereditary kind, and it’s also the first time that the spontaneous phenotypes that lead to sporadic PD have been described. The researchers were also able to identify that the neuronal alteration leading to both types of PD are the result of altered autophagy (the process by which cells ‘spring clean’ themselves by degrading their toxic waste and damaged parts).

“As well as shedding light on some of the key players and pathological mechanisms of the disease, this means we now have a reliable experimental model that captures patients’ genetic complexity, displays the prominent features of PD, and can eventually enable the identification of new therapeutic strategies that may prevent or remedy PD-related neurodegeneration,” says Ángel. “In a wider context, it also reveals that iPSC-based technology may be used to explore other late-onset diseases, such as Alzheimer’s.”

Sánchez-Danés, A. et al (2012). Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson’s disease. EMBO Mol Med, in press