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Epigenetic modifications could lead to new IMID biomarkers, therapies
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BOSTON — Advances in the understanding of epigenetic modifications — changes in gene activity without changes in DNA sequencing — could lead to the development of new biomarkers and potential therapies for immune-modulated inflammatory diseases, according to a presentation given at the Interdisciplinary Autoimmune Summit.
The presenter, Joel Pekow, MD, assistant professor of medicine at the University of Chicago, said these modifications are brought on by environmental triggers and passed on to subsequent generations, even if the offspring is not exposed to that trigger. He said gaining more knowledge about the mechanisms through which these modifications occur could have a significant influence in the future diagnosis and treatment of diseases brought on by environmental triggers, such as immune-modulated inflammatory diseases (IMIDs).
“The environmental stimuli from one generation may affect the next generation and subsequent generations in their disease onset,” Pekow said. “We know environmental triggers are very important for many [IMIDs] and inflammatory diseases, but most of the studies have been done with the individual. Perhaps we should consider environmental impact on one or two generations before. Those may be just as important.”
Biomarkers that look at epigenetic modifications can potentially help physicians tell patients how their disease developed, as well as where it is going, according to Pekow.
For example, he and colleagues conducted a cross-sectional study of patients with ulcerative colitis to determine if looking for these epigenetic modifications could be used to see which patients could be at risk for cancer. They analyzed the microRNA expression of 42 patients, including 23 without neoplasia and 19 with proximal colonic neoplasia. They found a clear separation that helped them distinguish between the two groups, Pekow said.
Although he said potential therapies targeting epigenetic modifications might be a bit farther away, Pekow noted that several animal and small human studies looking into treatment options for arthritis, Schnitzler syndrome and other diseases have already been performed.
“I hope we’ll be able to tell our patients why they developed their disease, whether it was an environmental exposure to them or to previous generations, as well as identify ways to prevent these diseases through this understanding,” Pekow said. “I think we’re going to see an onslaught of new biomarkers in the next several years looking at these epigenetic modifications. We’re far away from bringing therapies targeting epigenetic modifications in IMID to the clinic, although these therapies have been developed and are available. I anticipate we’re going to see an increasing number of clinical trials in the next several years. Hopefully we’ll be able to harness this understanding to treat several [IMIDs] by targeting these mechanisms.” – by Alex Young
Reference:
Pekow J. “Epigenetics for the Clinician: What this Means for Managing IMIDs.” Presented at: Interdisciplinary Autoimmune Summit; April 27-29, 2018; Boston, Mass.
Disclosures: Pekow reports serving on the advisory board for Janssen and Pfizer; being a consultant for CVS Caremark and Verastem; and receiving grants from AbbVie and Takeda.
Editor’s note: This article was updated on April 28 with clarifications from the presenter.