Parkinson‘s Disease is a common neurodegenerative disorder that is believed to affect about 10 million people worldwide. In contrast, Gaucher disease is a rare lysosomal storage disorder that affects about approximately 1 in 40,000 to 60,000 people in the world. Researchers and clinicians who studied Gaucher disease realized that that patients with Gaucher disease were more likely than other people to have Parkinson‘s disease, but the way in which the two conditions were related was not at all understood. It is now known that Gaucher disease, Parkinson‘s disease, and another neurodegenerative condition, Lewy body dementia (LBD) all involve abnormal proteins. Mutations in the glucocerebrosidase (GBA) gene, which encodes the lysosomal enzyme that is deficient in Gaucher disease have been shown to both important and frequent risk factors for Parkinson’s disease and related disorders, such as LBD. As a result of the defect in GBA, patients with Gaucher disease have increased levels of a molecule called α-synuclein. It is now known that aggregates of this molecule contribute to the cascade of events that promote neuronal dysfunction in Gaucher disease as well as the pathology of Parkinson‘s disease. Understanding the relationship between α-synuclein and both neurologic symptoms in patients with Gaucher disease and those in patients with Parkinson‘s disease increased the focus on therapies with the potential to treat both diseases. Molecular chaperones aimed at correcting defects in the cellular manufacture of GBA in patients with Gaucher disease have been studied since the early 2000‘s and medications in this class are now in late-stage clinical development. Remarkably, this approach to restoring GBA function and normalizing levels of α-synuclein is now under development for the treatment of Parkinson‘s disease. This underscores the potentially very broad importance of understanding the pathology of rare diseases and development of effective therapies. This enterprise will not only enhance the lives of patients with these conditions, but benefits may also to extend to those with other more common serious diseases.
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