The sequencing of the exome (the coding region of the genome) of more than 2,000 patients with familial Parkinson’s disease, and its comparison with data from nearly 70,000 healthy subjects, led to the discovery of a mutation in the RAB32 gene in 0.7% of Parkinson’s disease patients. The international study was coordinated by the University of Massachusetts and also involved researchers from the IRCCS Istituto Auxologico Italiano and the University of Milan. The results have been published in the journal Nature Genetics.

The results obtained during the project help to explain the genetic causes and pathogenetic mechanisms of the disease. Indeed, the research has shown how mutation of the RAB32 gene significantly increases the kinase activity of the LRRK2 protein, whose mutations represent one of the most common genetic forms of Parkinson’s disease. This results in the development of the neurodegeneration typical of this disease.
‘This study represents a significant step forward in the understanding of Parkinson’s disease,’ commented Nicola Ticozzi, director of the U.O. of Neurology at Auxologico and associate professor of Neurology at the University of Milan, co-author of the study. ‘The identification of a new disease-associated gene offers new opportunities for research and treatment. Indeed, knowing that the RAB32 gene is involved in the pathogenesis of the disease will make it possible to explore new biological pathways and potential therapeutic targets.’ From a practical point of view, this discovery could firstly improve the ability to diagnose Parkinson’s disease earlier, especially in familial cases, allowing early intervention. Secondly, a better understanding of the role of the RAB32 and LRRK2 genes in the disease could lead to the development of new targeted drugs that act on these specific pathogenetic mechanisms, thus improving the available treatment options. The resulting improvement in the diagnosis and treatment of Parkinson’s disease could help improve the quality of life of patients and reduce the economic and social burden associated with this disease.

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