Overview

Our focus is finding and assigning function to the genes involved in movement disorders, primarily Parkinson's disease (PD) and Lewy body dementia. We create etiologic, genetic models of the disorders and work with the Pharmaceutical Industry to develop novel drugs with which to halt their progression.

Parkinsonism is an insidious and progressive clinical syndrome that results from genetic and environmental factors. Over the last decade, Professor Matthew J. Farrer has built an international team of geneticists, neurologists and neuroscience researchers, and has established a world leading laboratory in Parkinson's disease research. Current research collaborations span more than 20 countries in five Continents. The Neurogenetic laboratories are part of a Udall Center for Excellence in Parkinson’s disease Research at the Mayo Clinic. The initial misson of the Neurogenetics laboratories at the Mayo Clinic in Jacksonville was to identify the underlying genetic causes of PD and related neurodegenerative disorders. Subsequently, the genes and mutations identified have been used to create experimental models of the disease, to understand the biological pathways peturbed and to develop novel therapeutic strategies aimed at halting disease progression.

In the last decade, mutations in seven genes have been identified that cause parkinsonism to be genetically inherited from one generation to the next. Prof. Farrer and his group have played an instrumental role in these monumental discoveries. In 2001, we showed that common genetic variability in alpha-synuclein (the first identified gene with a mutation causing parkinsonism (1997), and a major component of the protein aggregates (Lewy bodies) observed in the brains of PD patients) contributed to the risk of PD in the general population. In 2003, we identified alpha-synuclein multiplication mutations as a cause of early-onset parkinsonism with subsequent dementia. The discovery was made in a family that had been longtitudinally followed by Mayo Clinic neurologists for over 80 years. Affected family members have four copies of the alpha-synuclein gene rather than the normal two copies, therefore resulting in twice the protein amount. By 2007, we discovered many families with multiple copies of the alpha-synuclein gene, the largest kindred originating in Southern Sweden where family members still reside.

In 2004, in collaboration with researchers in Germany we identified the LRRK2 gene. LRRK2 protein has kinase activity and may provide a 'duggable target' for which novel therapies aimed at halting disease are now being developed. In 2005, we identified a ‘common’ LRRK2 mutation in patients from the US, Norway, Ireland and Poland that results in a single glycine to serine amino acid change in the protein at position 2019. In the US, approximately one million persons live with PD (~50,000 people are diagnosed every year), and in approximately ten thousand US patients LRRK2 G2019S is the cause. In collaboration with Tunisian neurologists in North Africa, we have since found the frequency of LRRK2 G2019S is highest, and the cause of PD in ~30% of patients of Berber-Arab descent.

The Udall Center for Excellence in Parkinson’s disease Research at the Mayo Clinic integrates Genetic, Clinical and Neuropathological Cores and provides support for number of research Projects. The Clinical Core lead by Prof. Zbigniew Wszolek is a multi-national effort to identify and characterize multiplex families with PD (with 2 or more affected family members) for genetic studies of PD. The Clinical Core also recruits and follows sporadic PD patients and arranges for postmortem studies. The Neuropathology Core lead by Prof. Dennis Dickson, performs postmortem evaluations of PD, provides histologic support for projects and provides postmortem material collected through several different avenues for the research projects.