In an animal study a gene-based therapy inhibiting the production of a brain protein thwarted the development of Parkinson’s disease, according to a report published online in the Journal of Clinical by researchers at the University Of Pittsburgh School Of Medicine. The findings may throw new light on how genetic and environmental factors join to cause the disease. This in turn could lead to the development of treatments that may prevent the progression, which disables and kills millions of people worldwide every year.
Parkinson’s disease is characterized by the dysfunction of mitochondria, which make energy for cells, and the proliferation of Lewy bodies– clumps of the cellular protein α-synuclein within neurons, according to principal investigator Edward A. Burton, M.D., D.Phil. at Pitt School of Medicine. “Until now we have pursued these as separate lines of PD research,” says Dr Burton. “According to our data mitochondria and α-synuclein are prone to interacting damagingly in vulnerable cells.” Targeting α-synuclein might, therefore, be an effective treatment strategy.
The scientists set out to see what happens if the production of α-synuclein in the brain’s substantia nigra, home to the dopamine-producing cells that disappear as Parkinson’s progresses, is knocked out. For this, they used an innocuous virus called AAV2 to carry a strand of genetic code that blocks the production of α-synuclein into the neurons of mouse models. They then exposed the animals to the pesticide rotenone, which inhibits mitochondrial function.
“Previous studies had proved that when exposed to rotenone, rats exhibit many features of Parkinson’s disease that are seen in humans like movement problems, Lewy bodies, loss of dopamine neurons and mitochondrial dysfunction,” said co-investigator J. Timothy Greenamyre. “We found that our gene therapy prevented those symptoms from appearing, which is very exciting.”
The left side of the body is controlled by the brain’s right side and vice versa. So, it is significant that the rats which received the gene therapy on the right side of their brain showed no signs of stiffness or any of the other telltale symptoms of Parkinson’s on the left sides of their bodies. However, the right sides of their body showed all the signs of the disease.
Clearly, this was because the gene therapy administered on the right side of their brains protected them from rotenone. In contrast, the untreated animals developed progressive Parkinsonism and loss of dopamine neurons. Following this finding, the researchers aim to uncover the molecular pathways that enable α-synuclein levels to influence mitochondrial function and develop drugs that can target the underlying mechanisms.