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Anti-TNF Therapy: Could Inflammatory Bowel Disease Therapies Pave a Path to a Treatment for Parkinson’s?

A recent study by Inga and colleagues at the Mount Sinai Beth Israel Parkinson’s Foundation Center of Excellence in New York examined the incidence of Parkinson’s disease in inflammatory bowel disease patients. The authors were also interested as to whether exposure to anti-tumor necrosis factor therapy (anti-TNF) could possibly reduce the risk of the later development of Parkinson’s disease. In this month’s Whats Hot in PD? blog we will discuss the links between inflammatory bowel disease and also examine the intriguing possibility that anti-TNF or related approaches may one day be used as Parkinson’s disease treatments.

The idea that inflammation is an important factor in the development of Parkinson’s disease is not new and systemic inflammatory diseases may provide an important clue to pathogenesis. There are almost two million people in the United States suffering from inflammatory bowel disease and there has been great interest in its potential links to neurodegeneration. The LRRK2 (leucine-rich repeat kinase 2) geneMutations in this gene are the most common cause of inherited Parkinson’s. Researchers have identified more than 100 LRRK2 gene mutations that increase the risk of developing PD. It is particularly common in people of Ashkenazi Jewish, North African Arab Berber and Basque descent, and variants have also been found in Chinese and Japanese populations. This gene is also known as PARK8, denoting its link to Parkinson’s disease and the order in which it was found to have a connection to PD (8th). is a well-established risk factor for Parkinson’s disease. LRRK2 has also been strongly linked to Crohn’s disease, and this link has raised the question as to whether there is a relationship between inflammatory bowel and Parkinson’s disease. Ulcerative colitis is the other common inflammatory bowel disease, and although much less is known about its links to Parkinson’s disease there has been recent interest in exploring this area. Many inflammatory bowel disease studies include both Crohn’s disease and ulcerative colitis patients.

Inga and colleagues, in a recent issue of JAMA Neurology, examined administrative health insurance claims from approximately 170 million people (Truven Health MarketScan administrative claims database and the Medicare Supplemental Database) and observed that inflammatory bowel disease patients were 28% more likely to develop Parkinson’s disease. Even more intriguing was the observation that exposure to anti-TNF therapy was associated with a 78% reduction in Parkinson disease incidence.

Though the studies were observational and the results derived from analysis of data from health insurance claims, the idea that systemic inflammation plays a key role in Parkinson’s disease is intriguing. Anti-TNF or other anti-inflammatory therapies may be candidates for future clinical trials.

Selected References

Inga Peter, PhD; Marla Dubinsky, MD; Susan Bressman, MD; Andrew Park, PhD, MPH; Changyue Lu, MS; Naijun Chen, MS; AnthonyWang, PhD, MPH Anti–Tumor Necrosis Factor Therapy and Incidence of Parkinson Disease Among Patients With Inflammatory Bowel Disease. JAMA Neurology Online April 23, 2018

Witoelar A, Jansen IE, Wang Y, Desikan RS, Gibbs JR, Blauwendraat C, Thompson WK, Hernandez DG, Djurovic S, Schork AJ, Bettella F, Ellinghaus D, Franke A, Lie BA, McEvoy LK, Karlsen TH, Lesage S, Morris HR, Brice A, Wood NW, Heutink P, Hardy J, Singleton AB, Dale AM, Gasser T, Andreassen OA, Sharma M; International Parkinson’s Disease Genomics Consortium (IPDGC), North American Brain Expression Consortium (NABEC), and United Kingdom Brain Expression Consortium (UKBEC)Investigators. Genome-wide Pleiotropy Between Parkinson Disease and AutoimmuneDiseases. JAMA Neurol. 2017 Jul 1;74(7):780-792. doi:10.1001/jamaneurol.2017.0469. PubMed PMID: 28586827; PubMed Central PMCID:PMC5710535.

You can find out more about our National Medical Director Dr. Michael S. Okun by visiting the Center of Excellence University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life.

What's Hot in PD?
Tue, 05/08/2018
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