Research suggests new paths for combined therapeutic strategies

Health

There are genetic connections between the chronic condition inflammatory bowel disease (IBD) and the incurable Parkinson’s disease (PD), according to researchers at the Icahn School of Medicine at Mount Sinai Medical Center in New York. 

The significant discovery – just published in the journal Genome Medicine titled, “The landscape of rare genetic variation associated with inflammatory bowel disease and Parkinson’s disease comorbidity, highlighted the potential for joint therapeutic strategies to target these two disabling diseases.

IBD refers to ulcerative colitis and Crohn’s disease in which the patient suffers from chronic inflammation of the gastrointestinal tract, risking damage to the digestive system. Both of them involve diarrhea, rectal bleeding, weight loss, weakness, and abdominal pain. 

Parkison’s disease is a brain disorder that causes unintended or uncontrollable movements, such as shaking, difficulty with balance and coordination, and stiffness whose symptoms usually begin gradually and worsen over time.

The team, led by Dr. Meltem Ece Kars, a postdoctoral researcher at the Bronfman Institute for Personalized Medicine; genetics and genomics Prof. Yuval Itan; and genetics Prof. Inga Peter, 

The team used advanced genomic analysis techniques to investigate the genetic overlap between IBD and PD. Their findings point to mutations in the LRRK2 gene as a common element connecting both conditions and identified novel genes that are likely to be affected in people suffering from both IBD and PD.

Genetic links

A DNA analysis of the remains of four individuals from Tylos-period Bahrain (300 BCE to 600 CE), the first ancient genomes from Eastern Arabia, revealed the malaria-protective G6PD Mediterranean mutation in three samples. Illustrative. (credit: INGIMAGE)

Kars explained: “We’ve found that IBD and PD are caused by certain shared genetic factors, including variants in LRRK2 and other genes previously unknown for this combined condition. This could dramatically change our approach to these diseases, allowing for therapies that target both conditions simultaneously.”

The study analyzed data from the Mount Sinai BioMe BioBank, the UK Biobank, and a group of 67 patients diagnosed with both IBD and PD from the Danish National Biobank. This combined dataset enabled the researchers to explore high-impact rare genetic variants and identify new genes and biological pathways that contribute to IBD-PD comorbidity.

“Our research not only links these two diseases genetically but also sets the stage for new forms of treatment, and potentially prevention strategies, that could lessen the burden of these diseases on patients,” Dr. Kars said.

The researchers used a variety of computational methods to uncover significant associations between the LRRK2 gene variants and the co-occurrence of IBD and PD, including the network-based heterogeneity clustering approach that they have found to be very effective for gene discoveries in small cohorts that cannot be analyzed by traditional gene association methods. Their analysis also revealed several pathways related to immunity, inflammation, and autophagy – the body’s cellular recycling system – that are involved in both conditions.

These discoveries have potential implications across numerous medical fields, suggesting that understanding genetic factors could lead to better-targeted therapies. The study underscores the importance of genetic research in developing personalized medicine approaches that could improve treatment for patients with both diseases.

The promise of these findings extends beyond current treatments. “By pinpointing the genetic underpinnings common to both IBD and PD, we pave the way for innovative treatments, whether through the development of novel drug targets or the repurposing of existing drugs, that could potentially tackle the root causes of these conditions,” Kars added. The results of this study could also influence future research directions, encouraging a more integrated approach to studying diseases 

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