The use of nonsteroidal anti-inflammatory drugs, such as aspirin, and the immune system have been linked to late-onset Parkinson’s Disease, according to research conducted by a team of researchers including members of Hopkins’ Center for Inherited Disease Research.
Their work, published in this month’s issue of Nature Genetics, utilized a genome-wide association study among 2,000 patients with Parkinson’s and 1,986 unaffected individuals.
The researchers discovered a connection between the HLA, a group of genes located on chromosome six that encode antigens essential to the immune system, and the disease. Links to Parkinson’s from two other genes, SNCA and MAPT, were further solidified by evidence gathered in this study.
The SNCA gene encodes a protein which is involved in signal trafficking and possibly the release of dopamine. Defects in SNCA have been linked to Parkinson’s.
The MAPT gene encodes a protein associated with microtubules, components of the cell’s skeleton, which can give rise to several different mRNA species through alternative splicing. Mutations in MAPT have been associated with various neurodegenerative disorders.
The researchers also found that use of nonsteroidal anti-inflammatory drugs (NSAIDs) had benefit in preventing the onset of Parkinson’s. These fever-reducing drugs include common, over-the-counter compounds such as aspirin and ibuprofen.
How the immune system and NSAID use are specifically related to the onset of Parkinson’s has yet to be determined.
“Conceptually, [the] immune system may have a triple function — genetic predisposition (HLA), protective as it tries to clear up whatever that is not supposed to be there (maybe infection, excess alpha-synuclein) and damaging as inflammation goes into over drive,” wrote Haydeh Payami, director of The Genome Institute at the New York State Department of Health Wadsworth Center, in an email with The News-Letter. “It would make sense that NSAIDS calm the inflammation and hence [are] somewhat protective.”
Parkinson’s Disease, which results in the degeneration of the central nervous system and subsequent impairment of motor skills, speech and other functions, has previously been thought to lack genetic precursors. Environmental factors have been the focus of much of the past research into the disease. Recent discoveries of genetic factors have lead to the development of genetic screening methods.
However, according to Payami, there is little that can be offered to help those who are diagnosed with Parkinson’s. “We have little to offer the patients — with a positive or negative test result — to improve their quality of life,” she wrote.
Identification of these new genetic precursors may prove helpful in future studies and clinical trials for drugs meant to treat or delay the onset of Parkinson’s, as genetic testing is essential for such studies of potential treatments.
“Here is the opportunity that can turn the failure of neuroprotective trials around. [Parkinson’s disease] clinical trials should be genotyping the patients and testing efficacy and safety conditioned on genotype. I bet some of the drugs that fell short of FDA benchmarks will surpass the requirement in patients with relevant genotype,” Payami wrote.
In their paper, the researchers note that new drug targets to treat or delay Parkinson’s disease may one day arise because of the newly identified genetic precursors.
More effective treatments may someday be developed to target these mechanisms as soon as further research explores these specific ties. Payami notes that because of their work, more researchers are becoming involved or have been expressing interest in research into Parkinson’s disease.
“So far, I have been approached by and set up collaborations with researchers who were not previously working on [Parkinson’s disease] to follow up the immune link - they are gurus in their respective fields,” Payami wrote. “I am thrilled.”
Payami and her collaborators have spent 18 years working together on this project and collecting patient data for their analysis. The Center for Inherited Disease Research here at the Hopkins School of Medicine contributed their genotyping services to this project.
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