Synedgen’s Senior Scientist Publishes New Research

Study sheds light on S. aureus virulence factor regulation

Claremont Calif. — September 21, 2018 — Research conducted by Synedgen Inc.’s Senior Scientist and colleagues from the University of Arkansas appears in the Journal of Proteome Research.

Allister J. Loughran, PhD, of Synedgen, and Stephanie D. Byrum, Karen E. Beenken, Lisa M. Orr, Aaron J. Storey, Samuel G. Mackintosh, Ricky D. Edmondson, Alan J. Tackett, and Mark S. Smeltzer from the University of Arkansas for Medical Sciences and Arkansas Children’s Research Institute conducted the research described in Label-free Proteomic Approach to Characterize Protease-dependent and Independent Effects of sarA Inactivation on the Staphylococcus aureus Exoproteome.

Staphylococcus aureus is an opportunistic Gram-positive bacterial species that exists as a commensal in a significant proportion of the healthy population. In individuals with a weakened immune system, the bacteria can become pathogenic and are capable of causing a diverse array of serious infections including pneumonia,sepsis, and osteomyelitis.

S. aureus treatment can be difficult with antibiotic resistance rates among isolates of S. aureus being high, new druggable targets are needed. The Staphylococcal Accessory Regulator (sarA), is one such target. Among other things, sarA regulates the level of proteases, proteins that degrade S. aureus virulence factors such as toxins. Without sarA, the bacteria are weakened and do not cause the same damage to the host.

Since this protein increases the degradation of the bacteria’s own proteins and new proteomic approach was needed to identify proteins that are changed as a result of loss of sarA function. Using an expanded dual proteomics approach, the team measured the abundance of proteins and characterized the exoproteome of wild type bacteria, sarA mutant bacteria and sarA mutants that also do not make the proteases. The analysis allowed for the separation of protein changes into two distinct groups, protease mediated changes and protease independent changes.The dual approach of conventional proteomic profiling and the new approach outlined in this publication, allowed for the identification of unique protein profiles from both methods, which provides for more complete and robust characterization of exoproteomes in the presence of proteases.

“This paper presented a comprehensive and robust method to analyze exoproteomes when endogenous proteases can impact the findings and highlights Allister’s expertise in investigating bacterial pathogenesis and host response,” remarked Synedgen President & COO Shenda Baker PhD.

This study was supported by the National Institutes of Health (R01AI119380, R21DA041822, P20GM121293, UL1TR000039, P20GM103625, S10OD018445 and P20GM103429).

The abstract is available at: https://pubs.acs.org/doi/10.1021/acs.jproteome.8b00288

About Synedgen

Synedgen is developing a new class of health care products based on glycomics, a revolutionary approach using glycopolymers to target mucosal and dermal interfaces. Synedgen uses its Glycomics Technology Platform (GTP) to discover and develop ultra-purified glycopolymers that enhance and mimic the innate immune system by targeting the cell surface glycocalyx and mucosal surfaces. Synedgen has successfully leveraged the GTP to develop marketed Prisyna oral care and Synedgen wound care products, as well as SNSP113, which has been licensed to Synspira and is currently in clinical development for the treatment of cystic fibrosis. Synedgen has established research and manufacturing facilities in Claremont, California.

 

 

Synedgen to Present New Treatment Options for Gastrointestinal Radiation Injury

Innovative Treatment to Reduce Cancer Therapy Complications

Radiotherapy is a well-established treatment for cancer, however pelvic radiotherapy can result in radiation proctitis, or inflammation and damage to the lower parts of the colon, for as many as 75% of radiation treated patients. In severe cases, this complication can result in the need to reduce the intensity of radiotherapy, ultimately jeopardizing a successful cancer prognosis.

Synedgen researchers are developing targeted therapies to reduce the incidence and severity of radiation proctitis by enhancing repair of gastrointestinal damage and modulating inflammation to allow for complete treatment or more aggressive treatment of pelvic cancers currently limited by radiation proctitis.

A poster presentation detailing this research has been accepted for display at Digestive Disease Week (DDW) 2016 at the San Diego Convention Center. The poster, entitled “Novel Therapeutic for the Repair of Gastrointestinal Radiation Injury”, will be exhibited on May 22, 2016 from 9:30 AM to 4:00 PM; lead author VP of Research Stacy Townsend PhD will be on hand to discuss the results from noon-2:00 PM.

The presentation highlights the efficacy of a specific molecule in Synedgen’s new class of targeted GI drugs, PAAG, on animal models of radiation proctitis. PAAG administered either orally or via enema significantly reduced local and systemic inflammation, and endoscopic examination confirmed improvement in the severity of proctitis compared to the control. A comparison between oral and enema administration showed that while both forms of treatment were highly effective, the oral delivery appears to be the optimal administration method.

“PAAG is a promising new drug candidate for reducing the inflammation and gastrointestinal damage associated with radiation therapy affecting the lower bowel,” stated Townsend. “We will continue to investigate its mechanisms of action in reducing radiation proctitis to enhance the development of this critically needed therapy.”

About Synedgen

Synedgen Inc. is an innovative biopharmaceutical company focused on targeting the mucosal interface to treat genetic and acquired disorders in the lungs and digestive tract. Synedgen’s Glycomics Technology Platform produces targeted drugs to meet unmet needs in treating inflammation, infection and mucosal damage. Synedgen’s Corporate Headquarters, Research Laboratories and Manufacturing Facility are in Claremont CA. Additional information can be found at Synedgen’s web site at www.synedgen.com.

About Digestive Disease Week

DDW is the world’s largest gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Approximately 15,000 GI professionals attended DDW 2015, plus an additional 2,000 to 3,000 exhibitors.

Synedgen President Shenda Baker Featured Presenter at the Grinnell-in-Los Angeles: Scientists Making a Difference in the World Conference

Synedgen President Shenda Baker will be a featured presenter at the upcoming Grinnell Scientists: Making a Difference in the World Conference

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