Old Drug May Get New Life in Parkinson's Prevention

Megan Brooks

April 25, 2018

Patients with inflammatory bowel disease (IBD) are at increased risk for Parkinson's disease (PD), but early treatment with anti–tumor necrosis factor (anti-TNF) therapy appears to offer protection, results of a large observational study suggest.

"We believe that our findings have potential clinical implications, including considering TNF-α inhibitors for Parkinson's disease prevention in high-risk individuals," Inga Peter, PhD, professor, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai in New York City, told Medscape Medical News.

The study was published online April 23 in JAMA Neurology.

Repurposing an Old Drug?

To compare the incidence of PD among adults with and without IBD and see whether the risk for PD among patients with IBD is altered by anti-TNF therapy, Peter and colleagues analyzed 16 years' worth of data on more than 170 million people in the Truven Health MarketScan claims database and the Medicare Supplemental Database. 

They identified 144,018 patients with IBD (mean age, 51 years; 44% men) and a matched cohort of 720,090 controls without IBD.

Overall, 1796 individuals had a diagnosis of PD. The incidence of PD was 28% higher in those with IBD (adjusted incidence rate ratio, 1.28; 95% confidence interval [CI], 1.14 - 1.44; P < .001). This association was seen in individuals with Crohn's disease and ulcerative colitis.

Of note, say the researchers, the incidence of PD was 78% lower in patients with IBD who received anti-TNF therapy compared with those who did not (adjusted incidence rate ratio, 0.22; 95% CI, 0.05 - 0.88; P = .03).

These findings support a role of systemic inflammation in the development of both PD and IBD, the researchers say. Further studies are needed to see whether anti-TNF therapy given to high-risk individuals may mitigate the risk for PD.

TNF inhibition has been considered as a therapeutic target for neurodegenerative diseases. Clinical trials have been conducted in Alzheimer's disease, amyotrophic lateral sclerosis, and multiple sclerosis  but not PD, "with some minor benefits observed in Alzheimer's patients only," said Peter. Several reasons could explain poor outcomes of these trials, she explained.

"One, TNF inhibition is ineffective once the disease is already established, and two, that TNF-α inhibitors do not cross blood-brain barrier. Our results indicate that reducing systemic inflammation earlier in life may help decrease the risk of Parkinson's disease. It can be testable in retrospective studies or in prospective clinical trials. However, the timing, dosage, and target population should be determined," said Peter.

Exciting Evidence

In a linked editorial,  Abby Olsen, MD, PhD, and colleagues from the Precision Neurology Program at Brigham and Women's Hospital in Boston, Massachusetts, note the study "builds on mounting genetic and molecular evidence supporting a causal association between the gut, systemic inflammation, and PD."

The analysis "provides exciting evidence in support of the concept of virtual repurposing of old drugs for new benefits. It turns pre-existing TNF inhibitor pipelines for treatment of IBD into potential research and development goldmines for treatment of PD," they write.

"Stay tuned for more surprising discoveries from treasure troves of big health data. Every physician knows how much can be learned by listening to a patient. Imagine how much might be learned by scaling this singular experience to torrents of digital health data from millions of patients," they add.

Peter has disclosed no relevant financial relationships. AbbVie provided salary support to three coauthors. One editorial author reports consulting for Sanofi and Biogen.

JAMA Neurol. Published online April 23, 2018. Article, Editorial  

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