Heparan Sulfate Therapeutic Opportunities
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Pharmaceutical heparin is a mainstay for treatment and prophylaxis in coagulation disorders. Pharmaceutical heparin is purified from pig intestines in a supply chain that has been contaminated in the past and is at risk of shortages. TEGA Therapeutics has modified the mammalian heparan sulfate biosynthetic pathway to produce recombinant heparin in cultured mammalian cells as an alternative to animal derived heparin.
TEGA's recombinant heparin has anticoagulant activity equal to pharmaceutical heparin. Genetic engineering has also reduced the risk of heparin induced thrombocytopenia, a life threatening side effect of treatment with heparin.
Many viruses, including coronaviruses, utilize cell surface heparan sulfate to infect the cell. TEGA Therapeutics has developed a non-anticoagulant heparan sulfate that binds the SARS-CoV2 spike protein and inhibits its binding to the cell surface, suggesting that recombinant heparan sulfate may be useful in preventing and treating COVID-19.
TEGA rHS09 was a potent inhibitor of SARS-CoV2 spike protein binding to human alveolar epithelial cells as published in the journal Cell.
Inflammation is driven by cytokine mediated recruitment and activation of inflammatory cells. The body's heparan sulfate is essential in this process. The addition of TEGA non-anticoagulant heparan sulfate can disrupt inflammation and may be useful in a variety of inflammatory diseases.
Emphysema is driven by chronic inflammation and proteolytic degradation of the lungs. Heparin blocks both of these processes but its use is limited by risk of bleeding. TEGA has developed a non-anticoagulant heparan sulfate that blocks a major enzyme that degrades the lungs with potency superior to heparin.
Heparin and heparan sulphate are inhibitors of human leucocyte elastase. Clin Sci (Lond). 1991. Link to PubMed.
Inhaled nebulised unfractionated heparin improves lung function in moderate to very severe COPD: A pilot study. Pulm Pharmacol Ther. 2018. Link to PubMed.