Researchers at the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s Hospital and Baylor College of Medicine have developed a mouse model that closely mimics both early non-motor symptoms and motor difficulties associated with Parkinson's disease. This significant advancement in neurodegenerative disease research was led by Dr. Huda Zoghbi, Distinguished Service Professor at Baylor, director of the Texas Children’s NRI, and a Howard Hughes Medical Institute investigator.
Dr. Zoghbi’s team used CRISPR-Cas9 technology to introduce a known Parkinson's disease-causing mutation, G51D, into the SNCA gene in mice. The research was published in the Proceedings of the National Academy of Sciences.
Parkinson's disease affects around 6 million people worldwide annually, including about 1 million Americans. The Parkinson's Foundation predicts that this number will increase by 20% in the U.S. by 2030. Currently, there is no cure for Parkinson's disease.
Dr. Zoghbi noted that one challenge in using mice to model Parkinson’s disease is that "even though mice can be aged, their neurons...are not exactly as challenged as human neurons that have been around for decades." This means that sometimes mice modified to carry human mutations do not exhibit all characteristics seen in humans because the disease takes longer to manifest.
More than 25 years ago, scientists found that mutations in the SNCA gene lead to an accumulation of α-Synuclein protein, causing loss of dopamine-producing neurons—a hallmark of Parkinson's disease. Several mouse models have been generated to overproduce mutant forms of α-Synuclein; however, these models did not display all features seen in humans with Parkinson's.
The new G51D mouse model shows early signs of Parkinson’s disease as early as three months old with symptoms appearing first in their olfactory systems and guts due to α-Synuclein accumulation. Motor difficulties and loss of dopamine-producing neurons appear between eight to ten months when the mice show gait and balance issues similar to those experienced by humans.
Kim characterized this G51D mouse model stating: "The mirroring of human early onset symptoms not displayed by other models means that these mice can be used to monitor biological changes during Parkinson’s progression."
The study involved several contributors from Baylor College of Medicine and NRI at Texas Children's Hospital including Joseph McInnes, Jiyoen Kim, Yan Hong Wei Liang, Surabi Veeraragavan, Alexandra Rae Garza, Benjamin David Webst Belfort, Benjamin Arenkiel, and Rodney Samaco. The work received support from grants provided by the Huffington Foundation, JPB Foundation, and HHMI.
