Scientists identify new strategy for treating inflammatory bowel diseases

Scientists at the Ben-Gurion University of the Negev (BGU) in Israel and Yonsei University in Seoul have identified a potential strategy to treat inflammatory bowel diseases (IBD). The method involves using peptides to reduce the effects of succinate, a proinflammatory molecule that gut bacteria release. The breakthrough could lead to a companion tool to diagnose and treat inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease.

The gut levels of succinate are considerably higher in macrophages of IBD patients, according to BGU professor Ehud Ohana. Furthermore, IBD patients have altered succinate-metabolizing bacteria that likely results in inflammation-inducing succinate surges. The international research team reported slowing succinate absorption by deploying peptide sequences that mimic the binding site within succinate binding enzymes.

The researchers developed a method of targeting and chelating surplus succinate in IBD patients. To do so, they used peptide sequences mimicking succinate binding sites.

Pharmaceutical companies also use succinate as an excipient. “Such treatments can have long-term side effects, and none address the root causes underlying IBD, which are largely unknown,” Ohana said. After ascertaining that IBD is at least partially the result of gut bacteria changes and succinate build-up, chelation could reduce the chronic inflammation at the heart of IBD. “Furthermore, our therapeutic peptides are identical to molecules that naturally exist in our body and are therefore unlikely to provoke a harmful immune reaction,” Ohana added.

“The research was first inspired by our interest in identifying new metabolic communication pathways between bacteria and host cells,” Ohana said over email. “By delineating the succinate transport pathway from bacteria to macrophages, we identified a physiological process that, when impaired, may lead to chronic inflammation. Hence, we realized that the underlying cause for IBD and potentially other inflammatory diseases may be metabolic.”

The international research team is optimistic that their research will provide an alternative to antibiotics, steroids and biological treatments deployed for IBD.

A Cell Reports study summarizes the findings.

The scientists involved in the research are considering multiple pathways to commercializations. “The technology is in very early stages,” acknowledged Dr. Galit Mazooz-Perlmuter, senior VP business development, biopharma at BGN Technologies. “We are looking for a strategic partner that can promote the development it in areas where academia has less experience (regulation, lead optimization etc.),” he said over email. The researchers cold also establish a startup company based on the technology “in one of the incubators in Israel or with an entrepreneur that can raise money for the project,” Perlmutter said. “The second option has less likely, due to the early stage of the research. Although early, there is a great potential if it will work. IBD is a big market with limited treatments options.”