



Drugs that suppress a patient’s immune system are a necessity when battling a variety of diseases and after life-saving organ transplant procedures. Unfortunately, these essential drugs also come with an array of unwelcome potential side effects—namely increasing the patient's susceptibility to normally well-tolerated infections, which then become life-threatening. However now, new data from investigators at Washington University School of Medicine in St. Louis (WUSM) may help to add Parkinson’s disease (PD) onto the list of disorders that immunosuppressive drug users need not worry over. Remarkably, the WUSM team found that individuals who take drugs that suppress the immune system are less likely to develop PD.

Findings from the new study—published today in the Annals of Clinical and Translational Neurology, in an article entitled “Immunosuppressants and Risk of Parkinson Disease”—suggest that a person's own immune system helps nudge them down the path toward PD. Conversely, restraining the immune system with drugs could potentially prevent the neurological disorder, which is characterized by tremors, slow movements, stiffness, and difficulty walking.

“The idea that a person's immune system could be contributing to neurologic damage has been suggested for quite some time,” explained lead study investigator Brad Racette, M.D., professor of neurology at WUSM. “We've found that taking certain classes of immunosuppressant drugs reduces the risk of developing PD. One group of drugs, in particular, looks really promising and warrants further investigation to determine whether it can slow disease progression.”

Dr. Racette and his colleagues analyzed millions of medical records, developing an algorithm to predict which people would be diagnosed with PD. As they mined the data, the researchers discovered that people with several types of autoimmune diseases, including ulcerative colitis, were less likely to be diagnosed with PD than the general population. The autoimmune diseases were a mixed bag, linked to myriad glitches in the immune system and affecting a variety of organ systems. It was hard to see how such a hodgepodge of immune system malfunctions all could end up having the same beneficial effect.

“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,” the authors wrote. “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.”

Interestingly, the researchers noted that many autoimmune diseases do have one thing in common: They are treated with drugs that dampen immune activity. While having an autoimmune disease may not be a good thing, the research team surmised that being treated for one could be.

During their analysis, the researchers identified 26 commonly prescribed immunosuppressant drugs, representing six classes of medications. The researchers determined which people in the dataset had been prescribed any of the drugs a year or more before the date of diagnosis or by a preset cutoff date. Prescriptions written in the 12 months before diagnosis or by the cutoff were excluded from ruling out any chance that the prescriptions might have been linked to early signs of the disease.

The WUSM team found that people taking drugs in either of two classes were significantly less likely to develop PD than those taking no immunosuppressants. People taking corticosteroids, such as prednisone, were 20% less likely to be diagnosed with PD, while those on inosine monophosphate dehydrogenase (IMDH) inhibitors were about one-third less likely.

When the researchers included specific autoimmune diseases in their analysis, the calculated risks didn't change, suggesting that the difference was due to using the drugs, not the underlying diseases they were treating.

The findings suggest that tamping down immunity with drugs may keep PD at bay. But doing so also makes people more susceptible to infectious diseases and cancer. The benefits of immunosuppressive drugs outweigh the costs for people with serious autoimmune diseases like rheumatoid arthritis. But doctors probably would hesitate to prescribe risky drugs to healthy people to stave off PD, especially since there is no reliable way to predict who is on track to develop the disease.

“What we really need is a drug for people who are newly diagnosed, to prevent the disease from worsening,” Dr. Racette noted. “It's a reasonable assumption that if a drug reduces the risk of getting PD, it also will slow disease progression, and we're exploring that now.”

Corticosteroids have many side effects, and doctors already try to minimize their use, so the investigators have turned their attention to IMDH inhibitors.

“Our next step is to conduct a proof-of-concept study with people newly diagnosed with PD to see whether these drugs affect the immune system that we'd expect,” Dr. Racette concluded. “It's too early to be thinking about clinical trials to see whether it modifies the disease, but the potential is intriguing.”



























