An Unexpected Link Between Gaucher and Parkinson’s Disease
For many years, it has been known that a link exists between Gaucher disease and Parkinson’s disease, but determining the exact mechanism behind this link has proven enigmatic. Recent research has begun to unveil the link by determining an inverse relationship between the production of two proteins associated with the two diseases. This provides hope for new and innovative treatments for Parkinson’s patients, and with continued research into this link, there is the possibility of developing better diagnosis and treatment methods for both diseases.
Gaucher disease, a rare disease affecting 6,000 people in the United States, is a lysosomal storage disease characterized by a deficiency of the enzyme glucocerebrosidase, also known as GCase.1 This deficiency is caused by mutations to GBA1, the gene which encodes for the GCase enzyme, and allows for the accumulation of glycolipids within the lysosome of cells.1 Glycolipids are lipids attached to a carbohydrate, and they play important structural roles within a cell. Their accumulation in the lysosome, however, results in the lysosome becoming engorged.2 The collection of engorged lysosomes in a cell causes the formation of Gaucher cells (Figure 1), disrupting the cell’s normal function and giving rise to the symptoms of Gaucher disease.2
Though the symptoms experienced by Type 1 Gaucher patients may vary, some of the most common include: low red blood cell counts, enlarged liver, osteoporosis, and bruising.3 In contrast, Parkinson’s disease has notably different symptoms including fatigue, tremors, and poor balance.4 Unlike Gaucher disease, which may exhibit symptoms as early as infancy, Parkinson’s is typically diagnosed later in life.4 Although the diseases may appear quite different at the surface, a link between the two was first observed in the 1900s.5 Since then, much research has gone into elucidating the specific biochemical mechanisms responsible for the association.
In the process of studying Gaucher disease, many different researchers have come across patients with symptoms resembling those of Parkinson’s. These patients have many similarities, including a low mean age of outset of 48.8 and rapid development of Parkinsonian symptoms.5,6 Upon further investigation, it was determined that relatives of Gaucher disease patients also have an increased risk of developing Parkinson’s. This may be because they carry a mutation to the GBA1 gene.7 But what is it about the GBA1 gene that increases an individual’s susceptibility to Parkinson’s? Current research indicates that the answer lies with the GCase enzyme.
Parkinson’s disease is a complex disorder caused by the formation of structures called Lewy bodies in nerve cells.8 These Lewy bodies are masses of protein that disrupt the transmission of signals between neurons, resulting in the characteristic symptoms of Parkinson’s disease. The bodies likely form due to an excess accumulation of one particular protein, which sticks together to form the blockade.8 It has recently been determined that there is a relationship between this Parkinson’s protein and the amount of GCase produced, indicating that individuals with small amounts of the former may have high amounts of the latter.2 The exact reason for this relationship is still not fully understood, but it may have tremendous impacts on treatments.
Current treatment for Gaucher disease typically includes enzyme replacement therapy, which involves the injection of the GCase enzyme.3 There is potential to use similar treatment methods for Parkinson’s, and it has recently been shown in mouse models that enzyme replacement therapy may be effective in relieving some symptoms.9
Ultimately, this current research provides hope for Gaucher and Parkinson’s patients alike and reminds the scientific community of the important message that research into rare diseases is not fruitless. Research such as this can make a huge impact on an individual’s life, while also propelling forward scientific discovery. As researchers continue to investigate the exact relationship between the two diseases, it is hoped that a greater understanding of the processes involved will lead to improved diagnosis and expanded treatment options for both diseases.
1. Bultron G, Box PO, Haven N, Box PO, Haven N. The risk of Parkinson’s disease in type 1 Gaucher disease. J Inherit Metab Dis. 2011;33(2):167-173. doi:10.1007/s10545-010-9055-0.
2. Aflaki E, Westbroek W, Sidransky E. The Complicated Relationship between Gaucher Disease and Parkinsonism : Insights from a Rare Disease. Neuron. 2017;93(4):737-746. doi:10.1016/j.neuron.2017.01.018.
3. Gaucher Disease - NORD (National Organization for Rare Disorders). NORD (National Organization for Rare Disorders). 2017. Available at: https://rarediseases.org/rare-diseases/gaucher-disease/.
4. About Parkinson’s - Parkinson Canada. Parkinson. 2017. Available at: http://www.parkinson.ca/site/c.kgLNIWODKpF/b.5184077/k.CDD1/What_is_Parkinsons.htm.
5. Neudorfer O, Elstein NGILADD, Abrahamov A, et al. Occurrence of Parkinson's syndrome in type I Gaucher disease. Q J Med. 1996;89:691-694.
6. Tayebi N, Callahan M, Madike V, Stubblefield BK, Orvisky E. Gaucher Disease and Parkinsonism : A Phenotypic and Genotypic Characterization. Mol Gene. 2001;73:313-321. doi:10.1006/mgme.2001.3201.
7. Schiffmann R, Lamarca ME, Nussbaum RL, Sidransky E. Parkinsonism among Gaucher disease carriers. J Med Genet. 2004;89:937-941. doi:10.1136/jmg.2004.024455.
8. Yoshikawa K. Early pathological changes in the parkinsonian brain demonstrated by diffusion tensor MRI. J Neurol Neurosurg Psychiatry. 2004;75(3):481-484. doi:10.1136/jnnp.2003.021873.
9. Sardi SP, Clarke J, Viel C, et al. Augmenting CNS glucocerebrosidase activity as a therapeutic strategy for parkinsonism and other Gaucher-related synucleinopathies. Proc Natl Acad Sci USA. 2013;110(9):3537-3542. doi:10.1073/pnas.1220464110.
Cite This Article:
Coles V., Chan G., Palczewski K., Lewis K., Ho J. An Unexpected Link Between Gaucher Disease and Parkinson’s Disease. Illustrated by Cindy Nguyen. Rare Disease Review. March 2018. DOI:10.13140/RG.2.2.27808.07680.