Scientists at the Buck Institute for Research on Aging have derived 10 induced pluripotent stem cells (iPSC) lines from Parkinson’s disease (PD) patients that carry the most common mutations associated with the disease. These cell lines and related genomic information will be made available to the larger scientific community, and PD models created using them may help to further understanding of the disease’s underlying causes, and to discover new diagnostic biomarkers and therapeutic drugs.
The cell lines are in the process of being deposited at a facility approved by the U.S. National Institutes of Health (NIH).
PD, a progressive and neurodegenerative disease, is characterized by the loss of control of balance, movement, and coordination, as well as a higher risk of dementia. While some patients have a family history of the disease, most cases are not inherited. Scientists believe the underlying causes of PD stem from a combination of genetic, environmental, and epigenetic factors, but questions remain. According to the National Parkinson Foundation, about 10% to 15% of Parkinson’s cases are thought to derive from mutations in specific genes, such as LRRK2, PARK2 and GBA.
Researchers, led by Xianmin Zeng, PhD, derived iPSC lines from skin cells donated by PD patients carrying the mutations SNCA, LRRK2, PARK2 and GBA. These cells were them reprogrammed to exhibit embryonic stem cell behavior, and induced to differentiate into dopaminergic neurons, the cells affected in PD. At each stage of the process, the scientists performed whole genome expression analysis.
“This work combined with dozens of other control, isogenic and reporter iPSC lines developed by Dr. Zeng, will enable researchers to model PD in a dish,” Dr. Brian Kennedy, Buck Institute president and CEO, said in a news release. “Her work, which we are extremely proud of, will help researchers dissect how genes interact with each other to cause PD, and assist scientists to better understand what experimental drugs are doing at the molecular level to decide what drugs to use based on mutations.”
A need exists for new and accurate PD models, since neurons obtained from patients have limited value, and animal models inadequately represent the human disease process.
“We think this is the largest collection of patient-derived lines generated at an academic institute,” said Dr. Zeng, who is working on a stem cell replacement therapy for PD. “We believe the lines and the datasets we have generated from them will be a valuable resource for use in modeling PD and for the development of new therapeutics.”
The research article, “Derivation, Characterization, and Neural Differentiation of Integration-Free Induced Pluripotent Stem Cell Lines from Parkinson’s Disease Patients Carrying SNCA, LRRK2, PARK2, and GBA Mutations,” was published in PLOS One.
The Buck Institute, a nonprofit and independent biomedical research center, is based in Novato, California.