Fibrosis: ILB®, Low Molecular Weight Dextran Sulfate (LMW-DS) Shows Anti-Fibrotic Effects in Pre-Clinical Trial

Fibrotic diseases are known to affect several vital organs in the body and are a major cause of mortality and morbidity. There has been a little success in treatment of these diseases so far. ILB®, the Low Molecular Weight Dextran Sulfate (LMW-DS) has shown promising results in a pre-clinical trial. It has been found to resolve inflammation and activate matrix remodelling in rodent and human disease models. Apparently, ILB® seems to have the potential to treat fibrotic diseases. Of particular interest is the possibility of anti-fibrotic treatment for glaucoma. But before getting approved, it needs to undergo further large scale clinical trials.

When inflammation is triggered due to factors like infections, autoimmunity, toxins, radiation, mechanical injury etc. lasts for longer period (chronic inflammation), the tissue remodelling and repair processes occur simultaneously. The repair process has two phases – regeneration (new cells of the same type replace injured cells) and fibrosis (connective tissues replaces normal cells). When uncontrolled, the repair process results in deposition of extracellular matrix (ECM) leading ultimately to replacement of normal tissue with permanent scar tissue.

Abnormal fibrosis as result of chronic and unresolved inflammation is common and is key pathology behind large number of diseases affecting vital organs like lung, liver, heart, pancreas, eye, brain, intestine, skin etc. These diseases are a major cause of mortality and morbidity worldwide. According to an estimate about 45% of all deaths are attributed to fibrosis. Treatment of fibrotic diseases is not usually successful for want of a suitable therapeutic agent that could resolve inflammation, arrest abnormal fibrosis, and activate regeneration of normal tissues thus restoring normal tissue homoeostasis without adverse effects. Any such therapeutic agent would be of great societal and economic significance.

In earlier study, ILB® has already been demonstrated to be safe in humans. In this study, researchers investigated low molecular weight dextran sulfates (LMW-DS) in rodent and human disease models. It was found that ILB®, the Low Molecular Weight Dextran Sulfate (LMW-DS) –

  1. modulates inflammatory and wound healing responses in cultured human cells,
  2. modulates expression of inflammatory and fibrogenic genes in cultured human cells, and
  3. reduces fibronectin levels in cultured human trabecular meshwork cells and resolves inflammatory scarring in a rodent model of glaucoma.

Thus, the results of this pre-clinical trial suggests that LMW-DS may resolve inflammatory scarring and promote functional tissue regeneration. This proof of concept makes ILB® a potential candidate for treatment of several fibrotic diseases including glaucoma.

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Source(s):

  1. Hill, L.J., Botfield, H.F., Begum, G. et al. 2021. ILB® Resolves Inflammatory Scarring And Promotes Functional Tissue Repair. Published: 07 January 2021. npj Regenerative Medicine volume 6, Article number: 3. DOI: https://doi.org/10.1038/s41536-020-00110-2 
  2. Wynn TA  2006. Cellular and molecular mechanisms of fibrosis. The Journal of Pathology Volume 214, Issue 2. First published: 27 December 2007. DOI: https://doi.org/10.1002/path.2277  

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