In a new study published in Nature Genetics, Paul Hop and colleagues describe the discovery of a gene responsible for a heritable form of Parkinson’s disease. The study was an international collaboration coordinated by the Kenna lab and multiple partners in the US and Italy. The research team used the RVAT software package developed by the Kenna lab and specialized computational infrastructure to analyze DNA from over 2,100 patients with familial Parkinson’s disease and 70,000 volunteers. The partnership with project MinE, an independent initiative to unravel the genetic basis of amyotrophic lateral sclerosis made the scale of the analyses possible.

“We’re very excited about this finding. This was the largest genetic analysis of familial Parkinson’s disease to date, and we believe that the discovery of the RAB32 mutation and it’s effect on LRRK2 open up important new research lines” – Paul Hop

Paul Hop is a PhD student at the UMC Utrecht Brain Center under the supervision of Kevin Kenna and Jan Veldink. Paul is also a lead developer for the RVAT analysis package. His analysis revealed a mutation in the RAB32 gene that significantly increased the risk of Parkinson’s disease. Subsequent investigations of this mutation in laboratory grown cell models revealed that the mutation led to abnormal increases in the activity of a key Parkinson’s related protein called LRRK2. Such abnormal increases in LRRK2 activity are  important in Parkinson’s disease. Furthermore, research community is already exploring this increase as a potential target for therapeutic intervention. Until now, only a handful of genes have been definitively implicated in heritable forms of Parkinson’s disease. The discovery of the RAB32 mutation and its effect on the LRRK2 protein are therefore an important step forward.

For more information about the study please see:

https://www.parkinson-vereniging.nl/archief/bericht/2024/06/10/nieuw-gen-voor-de-ziekte-van-parkinson-ontdekt

https://www.parkinsons.ie/new-gene-parkinsons-disease/