Treatment repurposing for inflammatory bowel disease using literature-related discovery and innovation

Abstract

Inflammatory bowel disease (IBD) incidence has been increasing steadily, most dramatically in the Western developed countries. Treatment often includes lifelong immunosuppressive therapy and surgery. There is a critical need to reduce the burden of IBD and to discover medical therapies with better efficacy and fewer potential side-effects. Repurposing of treatments originally studied in other diseases with similar pathogenesis is less costly and time intensive than de novo drug discovery. This study used a treatment repurposing methodology, the literature-related discovery and innovation (LRDI) text mining system, to identify potential treatments (developed for non-IBD diseases) with sufficient promise for extrapolation to treatment of IBD. By searching for desirable patterns of twenty key biomarkers relevant to IBD ( e.g ., inflammation, reactive oxygen species, autophagy, barrier function), the LRDI-based query retrieved approximately 9500 records from Medline. The most recent 350 records were further analyzed for proof-of-concept. Approximately 18% (64/350) met the criteria for discovery (not previously studied in IBD human or animal models) and relevance for application to IBD treatment. Many of the treatments were compounds derived from herbal remedies, and the majority of treatments were being studied in cancer, diabetes, and central nervous system disease, such as depression and dementia. As further validation of the search strategy, the query identified ten treatments that have just recently begun testing in IBD models in the last three years. Literature-related discovery and innovation text mining contains a unique search strategy with tremendous potential to identify treatments for repurposing. A more comprehensive query with additional key biomarkers would have retrieved many thousands more records, further increasing the yield of IBD treatment repurposing discovery.

Vaccine- and natural infection-induced mechanisms that could modulate vaccine safety

“…Other novel tactical treatments could be identified using our Literature-Related Discovery and Innovation (LRDI)-based treatment repurposing methodology [ 35 , 36 ].…”

“…The strategic treatments identified in the previous monograph are those contained within the immune system core literature. Additional novel strategic treatments could also be identified using our LRDI-based treatment repurposing methodology [ 35 , 36 ].…”

Tracking and Mining the COVID-19 Research Literature

“…We want to combine research knowledge accrued in COVID-19–related research with additional knowledge resident in other literature. Kostoff (Kostoff, 2011 , 2019 ; Kostoff and Patel, 2014 ) labels this “literature-related discovery and innovation,” but we will use LBD as shorthand.…”

“…Those categories comprise a number of components ( Supplementary Table 4 ), some of which could warrant LBD ventures to introduce remote research knowledge to enrich COVID-19 research focuses. We will seek expert synthesis and extension of our empirical topical information to identify problematic virus attributes, critical biomechanisms, and biomarkers and treatment approaches potentially suitable for “repurposing” (Kostoff, 2019 , 2020 ).…”

Pioglitazone-Mediated Attenuation of Experimental Colitis Relies on Cleaving of Annexin A1 Released by Macrophages

“…Thus, the search for drugs for treatment of IBDs has taken scientists to explore molecules beyond those designed to specifically treat IBDs and reassess drugs originally developed to treat other maladies ( Lloyd et al, 2019 ; Kostoff et al, 2020 ). Such is the case of thiazolidinediones, PPARγ ligands originally developed for treatments of diabetes, which have been explored to some success for treatment of IBDs.…”