BLACKSBURG, VA. – Landos Biopharma, Inc. (Landos) recently defined novel interactions in the gut mucosa mediated by nucleotide oligomerization domain like receptor X1 (NLRX1), a new immunoregulatory target. We provide evidence that NLRX1 functions as a metabolic and microbiome sensor responsible to maintaining tolerance and the integrity of the epithelial barrier.
The findings were published in a recent paper in Frontiers in Immunology.
The study uses a unique integration of next-generation sequencing technologies of host and gut microbiota with traditional immunology and innovative organoid cultures to confirm the potential of NLRX1 as an autoimmune therapeutic. By controlling the metabolism of glutamine and other amino acids in epithelial cells, NLRX1 maintains the expression of tight junction proteins to prevent microbial infiltration and the resultant recruitment of immune cells.
“IBD and other autoimmune diseases are rarely caused by single genetic errors alone but rather an accumulation of contributing factors spanning genetics, immunity, gut microbiome, diet, metabolism and environment,” said Bassaganya-Riera, Chairman and CEO. “Therefore, to design highly efficacious oral therapeutics we need to take a systems-wide view to identify new targets with multifaceted mechanisms like NLRX1.”
Unlike other NOD-like receptors, whose mutations and overexpression are drivers of inflammation in IBD, NLRX1 exerts regulatory effects that decrease the recruitment and activation of inflammatory immune cells, such as T helper 1 (Th1) cells and neutrophils. In line with this, the loss of NLRX1 worsens overall disease severity and allows for the expansion of an
inflammation-associated gut microbiome.
“Combined with our previous work in the Journal of Immunology, NLRX1 has proven effects in epithelial and immune cells making it a prime therapeutic target for IBD and other autoimmune diseases in the GI tract,” said Andrew Leber, Scientific Director. “Landos is continually evaluating novel strategies to generate an expansible therapeutic pipeline for autoimmune diseases and we believe that NLRX1 will prove as productive as LANCL2.”
Ongoing research efforts around the NLRX1 pathway have the potential to yield a new class of safer and more effective therapeutics that are orally active and target the GI tract. Landos has successfully developed new classes of oral therapeutics for autoimmune diseases that target the LANCL2 pathway. This NLRX1 program is leveraging a drug development pipeline that combines computational models with preclinical and translational studies.
About LANDOS – Accelerated Path to Cures
Landos Biopharma, Inc. (Landos) is an emerging biopharmaceutical company focused on the discovery and development of innovative first-in-class oral therapeutics for patients with autoimmune diseases. Landos’ lead asset, BT-11, is a novel small molecule targeting the Lanthionine Synthetase C-Like 2 (LANCL2) pathway in inflammatory bowel disease (IBD) that will enter clinical testing for Crohn’s disease and ulcerative colitis in 2018. Landos also has a robust pipeline of compounds for other autoimmune diseases.
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