Solulin (recombinant thrombomodulin) / PAION - LARVOL DELTA

Platelet hyperactivation and neutrophil extracellular traps promote thrombo-inflammation and glomerular endothelial dysfunction in diabetic kidney disease (#105) (GTH 2023) - "Therapeutic interventions (ASA, Anakinra, Solulin, GSK484, Ticagrelor, PSGL blocking) were performed in sub groups of mice with drugs starting at 16 weeks of diabetes until 24 weeks to study disease reversal. This results in aggravated disease course and impaired renal health in DKD. Inhibition of platelets or NETs is a promising therapeutic strategy for DKD."

Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Glomerulonephritis • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • Type 1 Diabetes Mellitus • CDH5 • IL1B • KLF4 • NLRP3 • NOS3 • SELP

Platelets and Neutrophil Extracellular Traps Promote Glomerular Endothelial Dysfunction and Barrier Disruption in Diabetic Kidney Disease (KIDNEY WEEK 2022) - "Therapeutic interventions (Aspirin, Anakinra, Solulin, GSK484) were performed after establishment of DKD to study disease reversal. This results in aggravated disease course and impaired renal health in DKD. Inhibition of platelets or NETs is a promising therapeutic strategy for DKD."

Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Glomerulonephritis • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • CDH5 • IL1B • KLF4 • NLRP3 • NOS3 • SELP • THBD

Cell Penetrating Peptides Conjugated to Anti-Carcinoembryonic Antigen "Catch-and-Release" Monoclonal Antibodies Alter Plasma and Tissue Pharmacokinetics in Colorectal Cancer Xenograft Mice. (PubMed, Bioconjug Chem) - "GALA and TAT were conjugated to 10H6 using SoluLINK technology that allowed the evaluation of peptide-to-antibody ratio by ultraviolet spectroscopy...Relationships between the predicted peptide conjugate isoelectric point (pI) and pharmacokinetic parameters were bell-shaped, where pI values around 6.8-7 exhibit the slowest plasma clearance and smallest distribution volume. The data and analyses presented in this work may guide future efforts to develop immunoconjugates with cell penetrating and endosomal escape peptides."

Journal • PK/PD data • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • CEACAM5

Platelets promote neutrophil extracellular traps mediated thrombo-inflammation and glomerular endothelial dysfunction in diabetic kidney disease (ISTH 2022) - "Therapeutic interventions (Aspirin, Anakinra, Solulin, GSK484) were performed in sub-groups of mice with drugs starting after 16 weeks of diabetes until 24 weeks to study disease reversal. Activated platelets (CD62P) and neutrophil extracellular traps (NETs; CitH3, NE, PAD4) were readily detectable in glomeruli of diabetic mice. Expression of inflammasome markers (NLRP3, IL1β) were positively correlated, reduced thrombomodulin (TM) expression was negatively correlating with NETs. In vitro, platelets exacerbate high glucose and NET induced endothelial dysfunction (p-eNOS, KLF2, KLF4 and TM), sterile inflammation (IL1β, NLRP3), cell death (TUNEL, Caspase-3) and glomerular filtration barrier disruption (enhanced FITC-albumin leakage, disoriented VE cadherin)."

Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Glomerulonephritis • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • CASP3 • CDH5 • IL1B • KLF4 • NLRP3 • NOS3 • THBD

Platelets and neutrophil extracellular traps promote thrombo-inflammation and glomerular endothelial dysfunction in diabetic kidney disease (GTH 2022) - "Therapeutic interventions (ASA, Anakinra, Solulin, GSK484) were performed in sub-groups of mice with drugs starting at 16 weeks of diabetes until 24 weeks to study disease reversal. Taken together, hyperglycemia promotes platelet-neutrophil interactions resulting in NETs, activation of clotting system, endothelial sterile inflammation, glomerular endothelial dysfunction, barrier disruption and cell death. This results in aggravated disease course and impaired renal health in DKD. Inhibition of platelets or NETs is a promising therapeutic strategy for DKD."

Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Glomerulonephritis • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • Type 1 Diabetes Mellitus • CDH5 • IL1B • KLF4 • NLRP3 • NOS3

"Minkälaisia ovat kuolemattomat solulinjat❓ Miten kantasolututkimus voi kehittää potilaiden hoitoa? Miten PCR-testi toimii❓" (@PfizerSuomi)

[VIRTUAL] Platelet and Extracellular Vesicle Mediated Inflammasome Activation Impairs Embryonic Survival by Reducing Placental Thrombomodulin Expression (ISTH 2020) - "TM was restored in EV-injected pregnant mice using soluble TM (solulin) or transgenic TM expression to establish causality... Genetic (NLRP3-/-) or pharmaceutical (anakinra) inflammasome inhibition did not rescue the TM-null embryos from lethality, establishing that the inflammasome activation does not cause lethality of TM-null embryos... These results establish a unidirectional relation of inflammasome activation and reduced trophoblast TM-expression, which contributes to the placental defect and embryonic demise in PE. Restoring TM levels may be a safe therapy in thrombo-inflammatory placental defects associated with excess platelet activation and placental inflammasome activation, as observed in PE."

Gynecology • Immunology • IL1B

Thrombomodulin dependent protein C activation is required for mitochondrial function and myelination in the CNS. (PubMed) - J Thromb Haemost - "These results uncover a novel physiological function of TM-dependent aPC generation within the CNS. Loss of TM-dependent aPC generation causes a neurological defect in healthy mice and aggravates EAE, which can be therapeutically corrected."

Journal • Biosimilar • Immunology • Multiple Sclerosis

No hyperfibrinolysis following subarachnoid or intracerebral haemorrhage: a prospective cohort study. (PubMed, Blood Coagul Fibrinolysis) - "To investigate fibrinolysis in the acute phase in SAH and ICH patients compared with healthy individuals, fibrinolysis after 24 h in ICH patients and the in-vivo effect of tranexamic acid (TXA) on fibrinolysis in SAH patients...Ex-vivo addition of solulin and prothrombin complex concentrate reduced fibrinolysis (P < 0.001). SAH and ICH patients showed no hyperfibrinolysis on admission. Fibrinolysis remained normal in ICH patients, and TXA treatment obliterated fibrinolysis in SAH patients."

Clinical • Journal

Thrombomodulin regulates platelet and extracellular vesicle mediated sterile inflammation in the placenta (GTH 2019) - "However, genetic (NLRP3-/-) or pharmaceutical (Anakinra, Apyrase) inflammasome inhibition did not rescue the TM-null embryos from lethality. These results demonstrate that EV-mediated platelet-activation, thrombo-inflammation and PE are associated with loss of placental TM and support a patho-physiological association of thrombophilia associated pregnancy complications and sterile inflammation. While loss of TM seems to be a consequence rather than cause of inflammasome activation, treatment with solulin efficiently prevented the EV-induced thrombo-inflammatory response and PE-like phenotype, presumably by restricting coagulation and platelet activation."

Thrombomodulin regulates platelet and extracellular vesicle mediated sterile inflammation in the placenta (GTH 2019) - "However, genetic (NLRP3-/-) or pharmaceutical (Anakinra, Apyrase) inflammasome inhibition did not rescue the TM-null embryos from lethality. These results demonstrate that EV-mediated platelet-activation, thrombo-inflammation and PE are associated with loss of placental TM and support a patho-physiological association of thrombophilia associated pregnancy complications and sterile inflammation. While loss of TM seems to be a consequence rather than cause of inflammasome activation, treatment with solulin efficiently prevented the EV-induced thrombo-inflammatory response and PE-like phenotype, presumably by restricting coagulation and platelet activation."