One of the motivating factors behind the launch of the CGRF many years ago was what we heard from the research community – the 21st century would be “The Century of Understanding the Brain” – that if we could fund research that would unravel the mystery of how Gaucher diesase affects the brains of young children, this science may very well unravel the mysteries of how over 20 other lysosomal diseases affect the brains of children. We realized then that this quest to find a cure was not soley for a rare orphan disease (neuronopathic Gaucher disease) but a quest to find cures for all lysosomal diseases that affect the brains of children which combined have a prevelance of 1:6000 births. Combined, certainly not an orphan disease but a set of diseases that are quite common and more often than not lead to death.
In our wildest dreams we did not think that the benefits of our research might impact an even larger segment of brain disease. However, researchers are currently pursuing a connection between Gaucher disease and Parkinson’s.
Parkinson disease is a common degenerative disease of the brain and parkinsonism refers to diseases that have similar clinical and pathological characteristics to Parkinson disease. The global term for this group of diseases is the synucleinopathies because of the common involvement of the alpha-synuclein protein in affected neurons.
In recent years it has become clear that mutations in GBA, the gene that codes for the lysosomal enzyme glucocerebrosidase that is deficient in Gaucher disease, are risk factors for the development of parkinsonism including Parkinson disease. That is, individuals who have GBA mutations, most of whom are carriers of such mutations (heterozygotes), are on average 5 times more likely to develop Parkinson disease compared to subjects that do not have mutations in this gene. This finding has been confirmed in a number of different ethnic groups.
Having GBA mutations as a risk factor means however that the vast majority of subjects with such mutations will not develop Parkinson disease or parkinsonism but that they are statistically more likely to develop these brain disorders. The mechanism of this phenomenon is not yet understood and may be related to the toxicity of the mutant glucocerebrosidase protein itself, to the partial deficiency of glucocerebrosidase or to another mechanism. Unraveling the relationship between Gaucher disease and the synucleinopathies will advance our understanding of the etiology, genetics, and pathogenesis of the both disorders, and could also lead to the development of new therapeutic strategies.
At the 2006 and 2008 Lysosomal Diseases and the Brain conferences hosted by the Children’s Gaucher Research fund representatives from the Parkinson research community were invited to share and compare research, expose themselves to cutting edge science on neuronopathic Gaucher disease, and engage in lively debate with regards to the viability of a connection between Gaucher disease and Parkinson’s. Since that time researchers within the Parkinson’s research community have initiated research with regards to this potential connection. In addition, the Michael J. Fox Foundation now looks seriously at funding research that pursues a better understanding of the potential connection between Gaucher disease and Parkinson disease.