Anti-Bin1 Treatment of Inflammatory Bowel Disease (IBD)

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease, is a debilitating autoimmune condition that is clinically challenging to manage effectively. In the U.S., the CDC estimates that 1.3% of adults (about 3 million) have been diagnosed with IBD.

Many IBD patients are diagnosed early in life. As a result of chronic gut inflammation they experience higher risks of colorectal cancer. Presently, other than general suppression of immunity or inflammatory signals, there are few strategies to limit or prevent IBD flare-ups in a disease-selective manner.

Building on their expertise in tissue barrier functions of the gastrointestinal tract, Lankenau Institute for Medical Research scientists have developed an antibody-based therapy that inactivates Bin1, a membrane-associated molecule that facilitates gut inflammation in the setting of IBD. This therapeutic technology based on novel MOA tightens the poor gut-barrier function found in IBD patients, thereby attenuating multiple sources of inflammation that are associated with a leaky gut barrier.

The scaffold and signaling molecule Bin1 modifies stress and inflammatory responses of cells under stress. In genetic studies in mice, LIMR scientists discovered that Bin1 ablation dramatically attenuated colonic inflammation and risks of colon carcinogenesis. In exploring therapeutic directions to mimic this effect, they discovered a cell-permeable anti-Bin1 antibody that is safe and effective when delivered systemically in preclinical models of IBD. Human colon tissue studies confirm observations that antibody uptake is sufficient to tighten barrier function, as measured physiologically or molecularly at the level of tight junction protein expression. Accordingly, anti-Bin1 acts to tighten colon barrier function, coordinately reducing mucosal lesions, crypt loss, lymphoid follicle rupture, and infiltration of neutrophils and lymphocytes into mucosal and submucosal areas of the colon.

The LIMR mAb-based strategy offers potential uses to treat multiple types of IBD by the unique mechanism of action of tightening gut barrier function.

 

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