Ben-Gurion University researchers to develop novel biological treatment for inflammatory bowel diseases
Inflammatory bowel disease (IBD) is devastating, affecting about five million people around the world, an estimated 1.6 million of them in the US alone, where there are 70,000 new cases of the diseases diagnosed each year.
IBD can be diagnosed at any age, but it is more likely to be seen in patients between the ages of 15 and 30. IBD includes two conditions –
Crohn’s disease and ulcerative colitis – that are characterized by chronic inflammation of the gastrointestinal (GI) tract. Prolonged inflammation results in damage to the GI tract.
Crohn’s can affect any part of the GI tract (from the mouth to the anus), and most often, it affects the portion of the small intestine before the large intestine/colon. Ulcerative colitis occurs in the large intestine (colon) and the rectum.
Some common symptoms of IBD are persistent diarrhea, abdominal pain, rectal bleeding/bloody stools, fatigue and weight loss.
The exact cause of IBD is unknown, but it is known to result from a defective immune system. A properly functioning immune system attacks foreign organisms, such as viruses and bacteria, to protect the body.
In IBD, the immune system responds incorrectly to environmental triggers, which causes inflammation of the gastrointestinal tract. There also appears to be a genetic component – someone with a family history of IBD is more likely to develop this inappropriate immune response.
IBD is diagnosed using a combination of endoscopy (for Crohn’s disease) or colonoscopy (for ulcerative colitis) and imaging studies, such as contrast radiography, magnetic resonance imaging (MRI) or computed tomography (CT). Physicians may also check stool samples to make sure symptoms are not being caused by an infection or run blood tests to help confirm the diagnosis.
There is as yet no cure, but several types of medications may be used to treat IBD – aminosalicylates, corticosteroids (such as prednisone), immunomodulators and the newest class approved for IBD, the “biologics”. Several vaccinations for patients with IBD are recommended to prevent infections.
Severe IBD may require surgery to remove damaged portions of the gastrointestinal tract, but advances in treatment with medications mean that surgery is less common than it was a few decades ago. Since Crohn’s disease and ulcerative colitis affect different parts of the GI tract, the surgical procedures are different for the two conditions.
Now, a novel and better therapeutic strategy for treating IBD is being developed by researchers at Ben-Gurion University of the Negev (BGU). They are isolating inflammation-inducing molecules secreted by gut bacteria.
The method, invented by Prof. Ehud Ohana of BGU’s department of clinical biochemistry and pharmacology; he and his lab team have shown that gut levels of succinate – a metabolic molecule involved in various biochemical processes in living cells – were markedly increased in IBD, corresponding to changes in succinate-metabolizing gut bacteria.
Several recent studies show that succinate acts as a pro-inflammatory metabolite, in particular driving inflammatory activity of macrophages.
The findings were published in the journal Cell Reports under the title “A transepithelial pathway delivers succinate to macrophages thus perpetuating their pro-inflammatory metabolic state.” The study was conducted by Moran Fremder, a graduate student in Ohana’s lab (in the MD/PhD program) and in collaboration with Prof. Jae Hee Cheon from Yonsei University in Seoul, South Korea.
The novel method targets and chelates excess succinate in IBD patients to attenuate its absorption, by using peptide sequences that mimic the succinate binding site in succinate binding enzymes. In parallel, biochemical methods will be used to measure succinate concentrations in biological specimens for a better diagnosis and content monitoring of IBD and related extra-intestinal symptoms. These technologies will be used as a companion tool to diagnose and treat IBD.
“Current treatments for IBD include antibiotics, steroids, and biological treatments aimed at inhibiting the activity of the immune system. Such treatments can have long-term side effects, and none address the root causes underlying IBD which are largely unknown,” explained Ohana.
“Our novel findings show that IBD is driven, at least partially, by changes in the activity of gut bacteria and by the accumulation of succinate in the gut, leading to chronic inflammation. Therefore, chelation of succinate can treat IBD and reduce inflammation. Furthermore, our therapeutic peptides are identical to molecules that naturally exist in our body and are therefore unlikely to provoke a harmful immune reaction.”
“This promising therapeutic approach developed by researchers at BGU is like that of diabetes treatment, wherein blood sugar levels are constantly monitored and adjusted using medication. It is, therefore, more dynamic and personalized than existing medications and is likely to significantly improve the quality of life of people suffering from IBD,” added Josh Peleg, CEO of BGN Technologies. “We have filed for patent protection and are now seeking a strategic partner for the further developing and commercializing this promising invention.”
BGN Technologies is BGU’s technology transfer company that brings technological innovations from the lab to the market and fosters research collaborations and entrepreneurship among researchers and students. To date, BGN Technologies has established over 100 startup companies in the fields of biotech, hi-tech and cleantech and has initiated leading technology hubs, incubators, and accelerators.
Over the past decade, BGN Technologies has focused on creating long-term partnerships with multinational corporations such as Deutsche Telekom, Dell-EMC, PayPal and Lockheed Martin, securing value and growth for the university as well as the Negev region.
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