Parkinson’s disease is a brain disorder that affects movement, balance, and coordination. It is one of the most common diseases of aging, but there are currently no treatments that can stop or slow it down. A protein called alpha-synuclein builds up in the brains of people with Parkinson’s disease and forms clumps known as Lewy bodies. These clumps may damage brain cells and are thought to play an important role in the disease.
In our research, we used a new type of gene-editing tool called CRISPR interference (CRISPRi) to lower the amount of alpha-synuclein made by brain cells. This version of CRISPR does not cut DNA—instead, it safely reduces the activity of a gene. We focused on the SNCA gene, which tells cells to make alpha-synuclein. Using special guide molecules called sgRNAs, we tested different spots in the SNCA gene to find the best way to turn it down.
We tested this system in brain cells grown from stem cells taken from a patient with a rare inherited form of Parkinson’s disease that causes too much alpha-synuclein. After using our CRISPRi tool, the cells made less alpha-synuclein and showed signs of improved health, including less stress and less damage to their DNA.
These results show that it is possible to use CRISPRi to carefully lower alpha-synuclein in brain cells. This could lead to a new and safer treatment for Parkinson’s disease and other related disorders. Our approach also helps researchers learn how much alpha-synuclein can be safely reduced without harming the cells.