It has long been suspected that the most common mutation linked to both sporadic and familial Parkinson’s disease wreaks its havoc by altering the function of mitochondria in neurons that produce the neurotransmitter dopamine. This theory is based on previous research involving fruit flies. Now, using stem cells derived from patients who have Parkinson’s disease, researchers at the Buck Institute have confirmed that finding in human cells for the first time.
In an opensource study published in the journal Stem Cell Reports, the researchers also provide a valuable tool for testing potential treatments for the progressive, incurable neurodegenerative disease. The team state that if they can find existing drugs or develop new ones that prevent damage to the mitochondria the medical community would have a potential treatment for Parkinson’s disease. To the group’s knowledge this is the first time a real and observable change in mitochondria in human cells affected by a Parkinson’s disease mutation has been shown.
The team explain that mitochondria are energy-producing organelles found in large numbers in most cells and are necessary for life. The Park2 mutation altered mitochondrial structure and function in dopamine producing neurons, causing them to die. Dopamine is an essential neurotransmitter which regulates movement and emotion.
The current study involved making mutations in the Park2 gene in well-characterized induced pluripotent stem cell (iPSC) lines as well as generating iPSC lines from skin cells of four patients who have Parkinson’s disease. In an extraordinary finding the same characteristics were observed in the dopaminergic neurons derived from patients as well as ones derived from the lines where the mutation was introduced.
The team state that the data findings promise to be significant in the search for treatments for an incurable disease, which affects nearly one million Americans and causes a progressive decline in movement and muscle control. Existing drugs can ease symptoms but often cause troubling side effects over time.
While using patient-specific iPSC lines has been held as a potential gold standard for testing potential therapeutics for Parkinson’s disease, the researchers state that there has always been concern that background genetic differences between patients would render the testing inconclusive for larger populations of Parkinson’s disease patients. According to the current study the findings address those concerns and paves the way for testing of compounds for Parkinson’s disease in human cells, an activity that is underway in the lab.
The team surmise that there are up to ten mutations linked to PD. The lab is developing human iPSC models based on mutations in Pink1, SNCA, Park7 and Lrrk2, which are those more closely implicated in Parkinson’s disease. The team is also involved in research aimed at getting a stem cell derived treatment for Parkinson’s disease ready for testing in humans.
Source: Buck Institute for Age Research