Immunosuppressants and risk of Parkinson disease

Abstract

We performed a population‐based case–control study of United States Medicare beneficiaries age 60–90 in 2009 with prescription data (48,295 incident Parkinson disease cases and 52,324 controls) to examine the risk of Parkinson disease in relation to use of immunosuppressants. Inosine monophosphate dehydrogenase inhibitors (relative risk = 0.64; 95% confidence interval 0.51–0.79) and corticosteroids (relative risk = 0.80; 95% confidence interval 0.77–0.83) were both associated with a lower risk of Parkinson disease. Inverse associations for both remained after applying a 12‐month exposure lag. Overall, this study provides evidence that use of corticosteroids and inosine monophosphate dehydrogenase inhibitors might lower the risk of Parkinson disease.

A plea to stop using the case‐control design in retrospective database studies

“…Perhaps the greatest success of the case‐control design stands its contribution to the evidence that smoking causes lung cancer . Since this landmark finding, researchers increasingly have applied the design, occasionally generating spectacular findings leading to headlines in major news outlets, such as a recent study linking anticholinergic drugs to an increased risk of dementia, or another recent study linking immunosuppressants to a lower risk of Parkinson's disease …”

COVID-19 infection may increase the risk of parkinsonism – Remember the Spanish flu?

“…Intriguingly, given that several recent reports support the notion that elevation of pro-inflammatory cytokines levels including IL-6 and IL-1β may hasten the onset of Parkinson's symptoms [2,3,19,20] and, concomitant intake of non-steroidal anti-inflammatory medication is inversely associated with a later diagnosis of Parkinson's disease [21]. Immunosuppression with steroids such as methylprednisolone may help in attenuating parkinsonism progression in selected patients [28].…”

Immunotherapies in Huntington's disease and α-Synucleinopathies

“…Azathioprine is an inosine monophosphate dehydrogenase (IMDH) inhibitor with an immunosuppressive function. Azathioprine treatment is associated with a lower risk of PD (121). Azathioprine inhibits IMDH which leads to the blockage of DNA synthesis and consequent suppression of circulating T-cell activity.…”

“…Three other antibodies, 1H7 (epitope aa 91-99), 5C1, and 5D12 (epitope aa [118][119][120][121][122][123][124][125][126] were also tested in Thy1 promoter-controlled human α-Syn transgenic mice (131). All these antibodies showed some beneficial effects on PD motor behavior deficits and neuropathology Several N-terminaldirected antibodies against α-Syn were also developed and tested in various rodent models of PD.…”