Effects of high-risk Parkinson's mutation are reversible

Researchers have found a new way to target and reverse the effects caused by one of the most common genetic causes of Parkinson's disease.
Mutations in a gene called LRRK2 carry a well-established risk for Parkinson's disease, however the basis for this link is unclear.
Scientists from the University of Sheffield found that certain drugs could fully restore movement problems observed in fruit flies carrying the LRRK2 Roc-COR Parkinson's mutation.
These drugs, deacetylase inhibitors, target the transport system and reverse the defects caused by the faulty LRRK2 within nerve cells.
"Our study provides compelling evidence that there is a direct link between defective transport within nerve cells and movement problems caused by the LRRK2 Parkinson's mutation in flies," said Dr Kurt De Vos from the Department of Neuroscience.

"We could also show that these neuronal transport defects caused by the LRRK2 mutation are reversible," added co-investigator Dr Alex Whitworth from the Department of Biomedical Sciences.

"By targeting the transport system with drugs, we could not only prevent movement problems, but also fully restore movement abilities in fruit flies who already showed impaired movement marked by a significant decrease in both climbing and flight ability," he said.
The LRRK2 gene produces a protein that affects many processes in the cell. It is known to bind to the microtubules, the cells' transport tracks. A defect in this transport system has been suggested to contribute to Parkinson's disease.

The researchers have investigated this link and have now found the evidence that certain LRRK2 mutations affect transport in nerve cells which leads to movement problems observed in the fruit fly (Drosophila).
The team used several approaches to show that preventing the association of the mutant LRRK2 protein with the microtubule transport system rescues the transport defects in nerve cells, as well as the movement deficits in fruit flies.
"We successfully used drugs called deacetylase inhibitors to increase the acetylated form of alpha-tubulin within microtubules which does not associate with the mutant LRRK2 protein," De Vos added.
"We found that increasing microtubule acetylation had a direct impact on cellular axonal transport.

"These are very promising results which point to a potential Parkinson's therapy. However, further studies are needed to confirm that this rescue effect also applies in humans," De Vos said.
The study is published in the journal Nature Communications.