Gene Therapy Shown to Remove Core Component of Parkinson’s Disease


Source: Rush University Medical Center

Summary: An international team of researchers has moved a step closer to developing a treatment to clear brain cells of a protein that is an integral cause of Parkinson’s disease.


Parkinson’s disease is a chronic, progressive movement disorder that affects the body’s ability to control movement. The condition is a result of damage to brain cells that produce dopamine, a chemical that relays messages to the parts of the brain that control movement, resulting in trembling, stiffness, slow movement and poor balance and coordination. Working with rats induced with a simulation of Parkinson’s disease, a research team from the Rush University Medical Center showed that a genetically engineered fragment of an antibody, called a nanobodycleared away toxic clumps of the protein alpha-synuclein after the team injected the nanobody into the rats’ brains. The hope is that once this therapy is introduced, it will continue to keep brain cells clear of the alpha-synuclein for the rest of the person’s life. The study findings were published in the journal Nature Parkinson’s Disease.

Brain disorder

Photomicrograph of regions of substantia nigra in a Parkinson’s patient showing Lewy bodies and Lewy neurites in various magnifications. Credit: Suraj Rajan

The team is testing is part of a rapidly evolving approach that deploys therapeutic nanobodies to invade cells as part of genetically-altered viruses. In this study, once inside the cell, the nanobody appears to have stopped the clumping of the dysfunctional α-syn that leads to a loss of nerve cells and, eventually, full-blown PD. Stopping the clumping should prevent the progression of the disease. The team created an “overexpression” (overabundance) of α-syn in the test rats’ brains. They then tested two types of the gene therapy, each on a different group of rats, and used saline in a control group, to see if the nanobodies could clear away the clutter inside those cells. One of the treatments, VH14*PEST, clearly worked best. It improved dopamine levels and reduced motor-function symptoms significantly better than the saline given the control group. VH14*PEST measurably improved the symptoms by one measure, the stepping test, and somewhat by another measure called the cylinder test. 

Prof. Jeffrey Kordower said, “We’re looking for ways to reduce alpha-synuclein levels, accumulation and toxicity resulting from the spread of alpha-synuclein around the nervous system” and further added, “down the road, this nanobody treatment could have implications for other parts of the brain as well, including the cortex, where misfolded α-syn may cause dementia.”


More Information: Diptaman Chatterjee et al. Proteasome-targeted nanobodies alleviate pathology and functional decline in an α-synuclein-based Parkinson’s disease model, npj Parkinson’s Disease (2018). DOI: 10.1038/s41531-018-0062-4


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