Researchers at the UCF College of Medicine’s Burnett School of Biomedical Sciences (BSBS) are using the CRISPR gene editing tool to gain insights into Parkinson’s disease, specifically to monitor the activity of the gene responsible for the production of the protein alpha-synueclein.
Parkinson’s disease affects approximately 1 million Americans, with new cases of the disease being diagnosed at a rate of around 60,000 each year. The Parkinson’s disease is a progressive neurological disease that results in damage to the brain causing body tremors and stiff and inflexible muscles. While the condition is not fatal, it can result in severe incapacity and reduces longevity.
While there are genetic factors known to play a role in the disease, for most individuals, the cause of the disease is unknown. Drugs can be used to limit some of the symptoms, although it is currently not possible to stop the progression of the disease nor reverse damage to the brain and neurons.
Researchers have discovered that Parkinson’s disease results in increased levels of the protein alpha-synueclein in brain cells. The protein is suspected of being toxic, causing the death of neurons as it accumulates in the brain. The researchers at BSBS believe that if drugs can be developed to inhibit aggregation of the protein in brain cells it may be possible to prevent damage to neurons.
The researchers have turned to the CRISPR gene editing tool to study the activity of the gene responsible for triggering the synthesis of alpha-synueclein.
CRISPR allows scientists to remove, add or edit specific genes. In this case, they used CRISPR to add a fluorescent marker next to the gene responsible for triggering the synthesis of alpha-synueclein. The marker allows the researchers to see when the gene is active as well as monitor protein levels.
The aim is now to introduce various compounds to determine their effect on gene activity and protein levels. The researchers chose kidney cells for the study rather than neurons as they are easier to work with and are currently testing various compounds.
While a cure of Parkinson’s disease may still be a long way off, the researchers hope their work will help to improve understanding of the disease and identify potential treatments. Compounds found to be effective at reducing alpha-synueclein will be assessed for toxicity and used in animal studies.
The use of CRISPR and the team’s new methodology are detailed in the paper – A novel tool for monitoring endogenous alpha-synuclein transcription by NanoLuciferase tag insertion at the 3′end using CRISPR-Cas9 genome editing technique – published in Nature Scientific Reports in April 2017.