BGU Researchers to Develop Novel Biological Treatment for Inflammatory Bowel Diseases

BGU researchers are developing a novel therapeutic strategy for treating Inflammatory Bowel Diseases (IBD) by sequestering inflammation-inducing molecules secreted by gut bacteria. The method, invented by Prof. Ehud Ohana (pictured below) from BGU's Department of Clinical Biochemistry and Pharmacology, is based on findings from Prof. Ohana's lab showing 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.

Inflammatory bowel diseases (IBD), primarily including Crohn's disease and ulcerative colitis, affect up to 1.5% of US adults and millions of people globally and lead to a severely impaired quality of life and significant morbidity. If remained untreated, IBD patients are at high risk for developing colon cancer. Currently, there is no cure for IBD, and treatments revolve around various methods for controlling inflammation by reducing the activity of the immune system. In severe cases, surgical intervention is required.

The findings were published in Cell Reports​ in a paper titled "A transepithelial pathway delivers succinate to macrophages thus perpetuating their pro-inflammatory metabolic state". This study was conducted by Moran Fremder, a graduate student in Prof. Ohana's lab (in the MD/Ph.D. program) and in collaboration with Prof. Jae Hee Cheon from Yonsei University, 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 Prof. 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, BGN Technologies. "We have filed for patent protection and are now seeking a strategic partner for the further developing and commercializing this promising invention."

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Amyloid Plaques May Cause Alzheimer's Disease By Accelerating Breakup of Neurotransmitters

Amyloid plaques comprising the beta-amyloid protein can effectively catalyze neurotransmitter degradation, according to a new study by BGU scientists. While amyloid plaques are the hallmark of Alzheimer's Disease and other neurodegenerative diseases, it is still not clear if, and how, such plaques contribute to disease progression and its pathological implications. This study offers an alternative explanation of how the plaques “poison” the brain by breaking up important neurotransmitters such as dopamine and adrenaline.

The study's findings were just published in the prestigious peer-reviewed Chem Catalysis, a Cell Press journal.

The research was led by Prof. Raz Jelinek and Ph.D. student Elad Arad, in collaboration with Prof. Hanna Rapaport and Avigail Baruch Leshem. The researchers discovered remarkable catalytic activity that was directly caused by beta-amyloid fibrils, not non-fibril organizations of the protein (smaller protein units such as monomers or oligomers). Importantly, neurotransmitter degradation has been observed in the brains of Alzheimer’s disease patients, suggesting that the fibril-catalysis phenomenon discovered by Jelinek and colleagues may indeed be physiologically significant.

"Our findings open intriguing new avenues of research into the molecular factors in neurodegenerative diseases that could bring us closer to therapeutic treatments," says Prof. Jelinek.

Prof. Raz Jelinek is the Vice President and Dean of Research & Development at BGU. He and his student Elad Arad are at the Department of Chemistry and the Ilse Katz Institute for Nanoscale Science and Technology (IKI). Prof. Hanna Rapaport is at the Avram and Stella Goldstein-Goren Department of Biotechnology Engineering and IKI. Avigail Baruch Leshem is a member of the Unit of Environmental Engineering.

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BGN Technologies Introduces New Method for Identifying Bacteria and Their Susceptibility to Antibiotics

Researchers at BGU, Shamoon College of Engineering, and Afeka Tel Aviv Academic College of Engineering have developed an innovative method for the rapid determination of the identity and antibiotic sensitivity of bacterial pathogens in urinary tract infections (UTI) in patients.

UTI is a common infection that affects any part of the urinary tract, but usually the lower urinary tract. In addition to the pain and discomfort associated with UTI, if left untreated or treated with ineffective antibiotics it can lead to complications such as permanent kidney damage and blood contamination. UTIs affect over 150 million people annually around the globe and is the most common outpatient infection in the US. In hospitals, UTIs account for 40% of all hospital-acquired infections.

The novel method enables detection of bacterial pathogens directly from urine samples in 30-40 minutes. The technology combines measurements of the infrared spectrum of the infecting bacteria with machine learning algorithms, to enable the simultaneous determination of both bacterial type at the species level and bacterial sensitivity to antibiotics.

The method has been tested on over 1,000 urine samples and was able to discriminate between bacterial species with approximately 97% accuracy and determine bacterial susceptibility to various antibiotics with approximately 85% accuracy.

The inventors include Prof. Mahmoud Huleihel (pictured here), head of the Shraga Segal Department of Microbiology, Immunology and Genetics​, Faculty of Health Science at BGU; Prof. Ahmad Salman from Shamoon College of Engineering and Dr. Itshak Lapidot from Afeka Tel Aviv Academic College of Engineering. BGN Technologies, the technology transfer company of BGU, has filed for patent protection and is now seeking a strategic partner for the further development and commercialization of this promising technology.

Prof. Mahmoud Huleihel, said, "The new technology offers a novel clinical decision-support tool for early and precise antibiotic recommendations, that will result in effective treatment. More broadly, our invention is timely, given the global emerging threat of antimicrobial resistance."

"This method for the identification of bacterial pathogens in UTI patients is an important and long-awaited solution for the management of UTI," said Josh Peleg, CEO of BGN Technologies. "Currently, identification of the bacterial pathogen and its antibiotics sensitivity is labor-intensive and can take up to three days, leading to treatment delays and potential complications. This novel solution can supply medical staff with results within 1 hour after collecting a urine sample, with very high accuracy and minimal effort. We are confident that this method has the potential to become a mainstay in hospitals and outpatient clinics alike."

Media Coverage:
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Preterm Babies at Greater Risk for Cerebral Palsy, According to BGU and Soroka Researchers

Preterm babies have a significantly higher risk for cerebral palsy (CP) and other long-term neurological disorders, according to researchers from Ben-Gurion University of the Negev and Soroka University Medical Center. The study is the first to demonstrate a critical cut-off for this significant complication in delivery before 25 weeks of gestation.

According to the study, published in Journal of Clinical Medicine, researchers identified the critical thresholds for preterm delivery that increase the chances of long-term hospitalizations for CP and other pediatric neurological disorders, including movement, developmental, degenerative, and psychiatric disorders.

CP is the most common cause of severe childhood physical disability and motor impairment. This group of permanent disorders, which forms in a fetus's or infant's developing brain, can also affect sensation, perception, cognition, communication, and behavior.

“Extremely premature exposure to the environment outside of the uterus may alter musculoskeletal and nervous system development, and shift the trajectory of motor development for otherwise healthy children," says Dr. Eyal Sheiner, vice dean for academic promotion at BGU's Faculty of Health Sciences and director of the Soroka Department of Obstetrics and Gynecology in Beer-Sheva.

In the large study, the researchers compared the outcomes of 220,563 deliveries over 23 years. They found that babies born before 25 weeks had a fourfold risk of developing long-term neurological issues and significantly increased CP rates. Each additional week of gestation, up to 37 weeks, appears to decrease the risk of long-term neurological disorders.

Other researchers that participated in the study include Dr. Gali Pariente and Dr. Shiran Zer of Soroka and BGU FOHS and Dr. Tamar Wainstock of BGU's School of Public Health. Shayna Miodownik is a student in the BGU Medical School for International Health.

Media Coverage:
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