Technique Generates More Accurate Parkinson’s Model

Researchers in Sweden and Canada have developed a method for producing more accurate model cells for Parkinson’s disease research. The technique, described in a recent issue of Stem Cell Reports, reprograms skin cells to mimic aged neuronsandmay aid research into the causes of the Parkinson’s and accelerate development of new therapies.

The ability to make virtually all cell types of the human body from induced pluripotent stem cells (iPSCs), which are embryonic-like cells generated from a patient’s skin by reprogramming, has opened new avenues for disease modelling in the lab.

However, a shortcoming of this technique is that the donor age-specific cellular features are erased during reprogramming, so that cells made from iPSCs typically resemble cells in the human embryo or fetus rather than cells in the adult or aged human individual. This has hindered the development of useful models for neurodegenerative diseases like Parkinson’s disease, which mainly affect older individuals and are therefore difficult to model with PSCs-derived neurons that lack many defining features of aged neurons.

Led by Janelle Drouin-Ouellet of the University of Montreal and Malin Parmar of University of Lund in Sweden, the team was able to preserve the aged characteristics of neurons by making them directly from the patient’s skin, without an iPSC intermediate. The researchers succeeded in turning skin cells from patients with Parkinson’s disease into dopaminergic (DA) neurons, which are the type of neurons progressively lost in the disease, by introducing a specific combination of neural-inducing genes into the skin cells.

Compared to the cells generated from iPS cells, this process of generating DA neurons preserved the aged genetic, epigenetic, and metabolic characteristics of the donor age. When compared to aged DA neurons from healthy skin donors, neurons from PD patients featured Parkinson’s-specific cellular defects, which now could be modelled for the first time from sporadic Parkinson’s patients which lack a known genetic mutation.

With this new tool, the researchers hope to model Parkinson’s disease-related neuronal defects from a much larger cohort of patients with the aim to identify identity causes of the disease as well as potential future therapies.