ShRNA Based Gene Therapy Prevents Neurodegeneration In Rat Model


Written by Kelsey on June 17, 2015. Posted in Blog

Brain Scan

Scientists at the University of Pittsburgh School of Medicine have found that gene therapy to reduce the production of a specific brain protein can successfully prevent the onset of Parkinsons disease in rats.

The study took an innovative approach to studying two causes of Parkinsons disease by looking at their combined effect on cells rather than looking at how each effects cells on an individual level.

Principal investigator Edward A. Burton, M.D.,D.Phil., associate professor of neurology, Pitt School of Medicine said, Our data show that mitochondria and a-synuclein can interact in a damaging way in vulnerable cells, and that targeting a-synuclein might be an effective strategy for treatment.

As Parkinsons disease progresses, dopamine-producing cells are lost. The team decided to examine what would happen if they stopped the production of a-synuclein in the brains substantia nigra, the same place where dopamine-producing cells are lost.

In order to stop the production of a-synuclein, researchers used genetic code to block the fabrication by delivery through a modified virus. This was carried out first on the brains of rats which were later exposed to a pesticide known to interfere with mitochondrial function. By combining the gene therapy and the pesticide treatment, scientists are able to look at the effect of both on the rats' brains.

Our previous work established that retenone exposure in rats reproduces many features of Parkinsons disease that we see in humans, including movement problems, Lewy bodies, loss of dopamine neurons and mitochondrial dysfunction, said co-investigator J. Timothy Greenamyre, M.D.,Ph.D., Love Family Professor of Neurology, and director of the Pittsburg Institute for Neurodegenerative Diseases at Pitt, in GEN News. We found that our gene therapy prevented those symptoms from appearing, which is very exciting.

Through an examination of the rats motor skills, the scientists concluded that by treating the left side of the rats brain, movement in their right sides did not suffer any changes whereas on the left side of the body, whose corresponding brain side was not was treated, movement became slow and stiff. From this, they concluded that the treated side of the brain was protected from the pesticide that alters mitochondrial function.

However, untreated animals and animals that received a control virus which did not reduce a-synuclein production, both developed progressive Parkinsonism and an acute loss of dopamine neurons.

This new development may provide a way to prevent the neurodegeneration that occurs in Parkinsons disease.

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