Inflammatory bowel diseases and Parkinson’s disease are often linked. Now researchers have identified the genes that probably link them. A researcher says that this could pave the way for treating one disease with drugs developed for the other disease.
Many people with Parkinson’s disease also have an inflammatory bowel disease such as ulcerative colitis or Crohn’s disease and vice versa. The association between these diseases has been known for some time, and now researchers have identified the genes that probably link them.
Genes influence the body’s response to inflammation, and according to a researcher behind the study, drugs developed for one disease might also benefit the other disease.
“This raises the possibility of completely new treatments for these diseases, and some studies have also indicated that some treatments for people with inflammatory bowel diseases can lower the risk of developing Parkinson’s disease. More studies are needed to investigate this potential, and this study indicates some areas in which drugs can affect both diseases,” explains Johan Burisch, consultant gastroenteroloigst, professor, PhD, DMSc, Gastrounit, medical division, Copenhagen University Hospital - Amager and Hvidovre.
The research has been published in Genome Medicine.
LRRK2 associated with both Parkinson’s disease and inflammatory bowel diseases
Several previous studies have found genetic overlap between inflammatory bowel diseases and Parkinson’s disease.
Mutations in the LRRK2 gene increase the risk of developing these diseases.
Several studies of people with either inflammatory bowel disease or Parkinson’s disease have shown that LRRK2 missense variants are associated with disease development. Variants are associated with increased risk of developing at least one of the diseases.
The special feature of LRRK2 is that it increases the production of certain autophagy-related proteins.
Autophagy plays an important role in the immune system’s ability to eliminate harmful cells, including bacteria and the body’s own cells. LRRK2 is thus involved in the immune regulation of inflammation.
“Dysregulated inflammation in the intestines can lead to the development of inflammatory bowel disease, and inflammation in the brain can lead to the breakdown of the dopamine-producing cells, which can lead to Parkinson’s disease,” says Johan Burisch.
Seventy-six people in Denmark have both diseases
In the new study, the researchers aimed to learn more about the genetic variants associated with these diseases. They therefore examined blood samples of 76 people with both inflammatory bowel disease and Parkinson’s disease from the Danish National Biobank.
They investigated the genetic links for the diseases and validated the results in two other large biobanks, including the UK Biobank, the world’s largest.
“The aim was to identify genes associated with risk that we did not know about beforehand and that can explain why people with inflammatory bowel disease have an increased risk of developing Parkinson’s disease and vice versa. Improving genetic understanding makes it easier to identify new drug targets and personalise the treatment to each individual,” explains Johan Burisch.
Fifteen genes link Parkinson’s disease and inflammatory bowel diseases
The new study confirms that LRRK2 has a role in these diseases and that LRRK2 variants are thus associated with increased risk for both inflammatory bowel diseases and Parkinson’s disease.
Further, the researchers identified for the first time 14 other genes associated with the development of both diseases.
Some of these genes are well known, such as NOD2, which also has an important role in regulating the immune system, whereas others were completely new and had never linked these diseases before.
“This is not surprising and confirms the theory that a systemic inflammatory disease can affect other locations other than the organ directly affected,” says Johan Burisch.
Personalised treatment is possible
According to Johan Burisch, the discovery may lead down several paths. He would like the result to be confirmed in other studies and also preferably with people differing in ethnicity, since the current study mainly comprises people of northern European origin.
Other relevant tasks include investigating the role of the various genes in the diseases and whether the genes or the associated proteins can become targets for new forms of treatment.
Finally, the study also provides insight into the fact that there may be genetic differences in the background for developing the two types of diseases and the links between them.
This indicates that more personalised treatment based on the genes that affect the diseases might benefit.
“Ultimately, we would like to find a treatment that works for the people who have an increased risk of developing both inflammatory bowel disease and Parkinson’s disease. There are already indications that some treatments can do this, and our study may explain why this is possible,” concludes Johan Burisch.
