Scientists led by The New York Stem Cell Foundation (NYSCF) Research Institute studied a pair of identical (monozygotic) twins, one affected and one unaffected with Parkinson's disease, another unrelated Parkinson's patient, and four healthy control subjects.
They were able to observe key features of the disease in the laboratory, specifically differences in the patients' neurons' ability to produce dopamine, the molecule that is deficient in Parkinson's disease.
Parkinson's disease is moderately heritable, but the mechanisms of this inheritance are not well understood.
"The unique scenario of identical twins, one with this disease and one without, allowed our scientists an unprecedented look into the mechanisms of Parkinson's disease," said Susan L Solomon, NYSCF Chief Executive Officer.
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This discordance suggests that multiple factors contribute to the development of Parkinson's disease, including both genetic and non-genetic factors.
To date, there has been no appropriate model to identify and test multiple triggers leading to the onset of the disease.
In the study, published in journal Cell Reports, a set of identical twins, both with a GBA mutation, provided a unique opportunity to evaluate and dissect the genetic and non-genetic contributions to the development of Parkinson's disease in one twin, and the lack of disease in the other.
Upon analysing the cell models, the scientists found that the dopamine-producing neurons from both twins had reduced GBA enzymatic activity, elevated alpha-synuclein protein levels, and a reduced capacity to synthesise and release dopamine.
In comparison to his unaffected brother, the neurons generated from the affected twin produced less dopamine, had higher levels of an enzyme called monoamine oxidase B (MAO-B), and poor ability to connect with each other.
This suggests that a combination therapy for the affected twin may be possible by simultaneously targeting these two enzymes.
The study was published in the journal Cell Reports.