A gene therapy to reduce production of a brain protein successfully prevented Parkinson’s disease from developing in rats, according to a study by the University of Pittsburgh.
Researchers said the findings, published Monday in the Journal of Clinical Investigation, could lead to new understanding of how genetic and environmental factors merge to cause the disease, which can cripple the nervous system affecting movement, speech and daily activities.
“For the person with Parkinson’s, I think this is one step closer to having an effective treatment that prevents the disease from progressing,” said Edward Burton, Pitt neurology professor and the study's lead investigator. “We’re still in animal models; there’s a lot of work to do.”
In previous work, scientists observed dysfunctional mitochondria, which power cells, and Lewy bodies, characteristic aggregates of protein, primarily alpha-synuclein, that develop inside neurons.
Mitochondria and alpha-synuclein can interact in a damaging way in vulnerable cells, he said.
Researchers wanted to see what would happen if they blocked the expression of alpha-synuclein cells in the part of the rats' brain where dopamine-producing cells – those lost as Parkinson’s disease progresses – reside, so they used a virus to transport a small piece of genetic code that blocks the proteins production in the neuron.
Rats were then exposed to the pesticide rotenone, which inhibits mitochondrial function. Prior research showed rotenone exposure in rats mimicked many of the same symptoms of Parkinson’s, including movement problems and a drop in dopamine production.
“Its subsequently been shown that people that are exposed to rotenone occupationally actually have an elevated risk of developing Parkinson’s disease," Burton said. "So we think that the model, at least in the biochemical mechanism and the clinical appearances both of the tissue and the rats afterwards, has a number of parallels with humans Parkinson’s disease.”
Each side of the brain controls the opposite side of the body. In the study, rats that received gene therapy to the right side of their brains didn't stiffen on their left sides, but their right sides did.
Burton said the research is ongoing.
