Where LRRK2 leads, other genes follow!

LRRK2  - as I said before, mutations in this gene are the most common cause of Parkinson's. When I started work on fly models of Parkinson's, I was given some good advice: just focus on LRRK2 because (even though genetic forms of Parkinson's are only about 1% of cases) this will help more people than working on any other gene. A second good reason is that it looks as if LRRK2 forms of Parkinson's closely resemble all the other, the non-genetic forms, including adult onset Parkinson's, the kind that appears in people aged > 60 years old. Working on LRRK2 proved a highly successful strategy, and we could show that young flies with the G2019S mutation in this gene have a very overactive visual system [1]. Old flies with this mutation have, as you might expect, really bad vision because the nerve cells in their eyes have died.

But I still get comments saying is this work relevant to other forms of Parkinson's? So we have looked at a range of other forms, focussing on early-onset forms, mediated by genes called PINK1 and DJ1. This week, we were able to publish our paper showing that, like the young LRRK2-G2019S flies, young flies with mutations in these genes (PINK1 and DJ1) show overactive visual systems [2]. Actually, the method we used to analyse flies was made by miniaturising a technique devised to analyse the vision of babies. We called this FlyTV - its not quite as simple as in our cartoon, but works really reliably. It showed that detailed physiology of the eye in these two mutants is quite revealing, and suggests that we might be able to develop a scheme to monitor both the occurrence and the progression of "Parkinson's" in our flies using visual stimuli. Some of our data even suggests that the very fine visual changes we see may occur before any movement problems occur. Because we used the technique for babies' vision to study flies, we hope the technology might be developed and applied to adults. Our hope is that any early high levels of visual signalling might be a warning sign to start seeking medical advice.

FlyTV - The flies get to watch a TV showing stripy patterns changing several times a second. © Ryan West et al - see ref [2]

1] http://dx.doi.org/10.1093/hmg/ddu159

2] http://www.nature.com/articles/srep16933