By Michelle Jaffee
University of Florida neuroscientists have discovered a novel insight into the pathophysiology of Parkinson’s disease by using stem cell technology to create human dopamine neurons from stem cells of a patient with a genetic mutation that causes Parkinson’s disease as well as stem cells of an unaffected healthy sibling.
The study, published in the journal Acta Neuropathologica Communications, examines the interaction of the protein α-synuclein with the activity of human dopamine neurons prior to their death in the context of Parkinson’s disease.
A research team led by UF neuroscientists including Min Lin, M.D., Ph.D., an assistant scientist in the department of neuroscience, and Phillip Mackie, an M.D.-Ph.D. fellow in the lab of Habibeh Khoshbouei, Pharm.D., Ph.D., used induced pluripotent stem cells, or iPSCs, which are derived from skin or blood cells. The stem cells came from a Parkinson’s patient carrying a genetic mutation called the α-synuclein triplication mutation, which produces more of the protein and leads to progressive loss of dopamine neurons.
“We found an administration of an FDA-approved drug called quinpirole partially restores the neuronal activity of Parkinson’s disease patients and slows the rate of neuronal loss,” said Khoshbouei, a professor of neuroscience and psychiatry and senior author of the paper. “Thus, our data suggest administration of quinpirole in Parkinson’s disease patients with this genetic mutation might reduce the rate of neuronal loss.”
The study’s methods provide a meaningful and clinically relevant pathway to examine the mechanism of progression of neurodegenerative diseases such as Parkinson’s prior to the degeneration of dopamine neurons, Khoshbouei said.
“This work will provide the technology to develop patient-specific therapeutic strategies,” she said.