NuSepin (taurodeoxycholic acid) / Shaperon - LARVOL DELTA

Safety, Tolerability and Pharmacokinetics of Intravenous Sodium Taurodeoxycholate, HY209, a GPCR19 Agonist Inhibiting Inflammasomal Activation. (PubMed, Drug Des Devel Ther) - "This study aimed to assess the safety, tolerability and pharmacokinetics (PKs) of HY209 after intravenous administration in healthy subjects...The baseline-adjusted maximum plasma concentration of TDCA demonstrated dose-proportionality in a HY209 range of 0.1-1.6 mg/kg. A single intravenous administration of HY209 was well tolerated and its systemic exposure showed dose-proportionality in a dose range between 0.1 and 1.6 mg/kg."

Clinical • Journal • PK/PD data • Infectious Disease • Septic Shock

Effects of intravenous inflammasome inhibitor (NuSepin) on suppression of proinflammatory cytokines release induced by cardiopulmonary bypass in swine model: a pilot study. (PubMed, Sci Rep) - "However, in the Nusepin group, IL-6 levels rapidly decreased when CPB was stopped and the proinflammatory reaction subsided. Furthermore, the dose of norepinephrine required to maintain a mean pressure of 60 mmHg was also lower in the Nusepin group."

Journal • Immunology • Inflammation • Systemic Inflammatory Response Syndrome • CXCL8 • IL1B • IL6 • TNFA

Effects Of Intravenous Inflammasome Inhibitor ( Nusepin ) On Suppression Of Proinflammatory Cytokines Release Induced By Cardiopulmonary Bypass In Swine Model. (ASA 2023) - "Our study demonstrated that the total amount of norepinephrine required to maintain a mean pressure was reduced by anti-inflammatory agents, NuSepin®. Moreover, the proinflammatory cytokine release tended to be inhibited. Further study will be needed for clarity, but the potential for clinical use of anti-inflammatory agents in non-inflammatory SIRS could be evaluated based on this study."

Anesthesia • Cardiovascular • Immunology • Inflammation • Systemic Inflammatory Response Syndrome • CXCL8 • IL1B • IL6 • TNFA

A study investigating the efficacy and safety of 2 doses of NuSepin® intravenous infusion in adult subjects with Covid-19 pneumonia (clinicaltrialsregister.eu) - P2 | N=60 | Completed | Sponsor: Shaperon Inc

New P2 trial • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Phase 2b/3 Trial of NuSepin® in COVID-19 Pneumonia Patients (clinicaltrials.gov) - P2b | N=1134 | Recruiting | Sponsor: Shaperon

New P2b trial • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • IL18 • IL1B • IL6 • TNFA

Clinical Trial to Investigate the Efficacy and Safety of NuSepin® in COVID-19 Pneumonia Patients (clinicaltrials.gov) - P2 | N=64 | Completed | Sponsor: Shaperon | Recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Potent suppression of hydrophobic bile acids by aldafermin, an FGF19 analogue, across metabolic and cholestatic liver diseases. (PubMed, JHEP Rep) - P2 | "The therapeutic strategy utilising aldafermin may be broadly applicable to other chronic gastrointestinal and liver disorders. The study is registered at Clinicaltrials.govNCT02443116 and NCT02704364."

Journal • Addiction (Opioid and Alcohol) • Fibrosis • Gastrointestinal Disorder • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • FGF19 • MRI

Serum metabolic signatures of subclinical atherosclerosis in patients with type 2 diabetes mellitus: a preliminary study. (PubMed, Acta Diabetol) - "Serum bile acids may be potential biomarkers for subclinical atherosclerosis in T2DM patients, which needs further confirmation."

Clinical • Journal • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Clinical Trial to Investigate the Efficacy and Safety of NuSepin® in COVID-19 Pneumonia Patients (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Shaperon; Trial completion date: Nov 2020 ➔ Apr 2021; Trial primary completion date: Nov 2020 ➔ Apr 2021

Clinical • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Reduced glycodeoxycholic acid levels are associated with negative clinical outcomes of gestational diabetes mellitus. (PubMed, J Zhejiang Univ Sci B) - "Total BAs (TBAs) remained stable, but glycodeoxycholic acid (GDCA) and taurodeoxycholic acid (TDCA) levels declined significantly in GDM...However, GDM patients with high HOMA-IR and low DI tended to have a higher cesarean delivery rate and younger delivery gestational age. In conclusion, GDCA provides a valuable biomarker to evaluate HOMA-IR and DI, and decreased GDCA levels predict poorer clinical outcomes for GDM."

Clinical • Clinical data • Journal • Diabetes • Gestational Diabetes • Metabolic Disorders

NASH-related increases in plasma bile acid levels depend on insulin resistance. (PubMed, JHEP Rep) - P=N/A | "Plasma bile acids have been proposed as NASH biomarkers. Herein, we found that plasma bile acids are only elevated in patients with NASH when significant insulin resistance is present, limiting their utility as NASH markers."

Journal • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity • Type 2 Diabetes Mellitus

Therapeutic Effects of Different Animal Bile Powders on Lipid Metabolism Disorders and Their Composition Analysis. (PubMed, Chin J Integr Med) - "Different animal bile powders had varying therapeutic effect against lipid metabolism disorders induced by high-fat diet, and bear bile powder demonstrated the most effective benefits. Bioactive compositions were different in different types of animal bile with a novel compound identified only in bear bile powder."

Journal • Dyslipidemia • Hepatology • Metabolic Disorders

Organ function, sphingolipid levels and inflammation in tunicamycin induced endoplasmic reticulum stress in male rats. (PubMed, Hum Exp Toxicol) - "ER stress was induced by tunicamycin (TM) and the ER stress inhibitor taurodeoxycholic acid (TUDCA) was injected before induction of ER stress...TUDCA administration decreased tissue CER levels, cPLA2 and COX-2 expression as well as prostaglandin E2 (PGE2) formation. These results signify that ER stress causes hepatic and renal toxicity as well as CER-induced PGE2 formation in liver and kidney."

Journal • Immunology • Inflammation • Renal Disease

Plasma metabolites associated with chronic kidney disease and renal function in adults from the Baltimore Longitudinal Study of Aging. (PubMed, Metabolomics) - "The metabolites associated with CKD and reduced eGFR suggest that several pathways, such as the urea cycle, the arginine-nitric oxide pathway, the polyamine pathway, and short chain acylcarnitine metabolism are altered in adults with CKD and impaired renal function."

Clinical • Journal • Observational data • Chronic Kidney Disease • Glomerulonephritis • Nephrology • Renal Disease

Effect of Lactobacillus rhamnosus Probiotic in Early Pregnancy on Plasma Conjugated Bile Acids in a Randomised Controlled Trial. (PubMed, Nutrients) - "A significant decrease of glycocholic acid (GCA) was found in older (age ≥ 35) women who received HN001 (p = 0.005), while GDM women showed significant reduced taurodeoxycholic acid (TDCA) (p = 0.018). Fasting conjugated BA was positively correlated with fasting glucose (r = 0.136, p = 0.020) and fasting insulin (r = 0.113, p = 0.036). Probiotic HN001 supplementation decreases conjugated BAs and might play a role in the improvement of glucose metabolism in women with pregnancy."

Clinical • Journal • Diabetes • Dyslipidemia • Gestational Diabetes • Metabolic Disorders

Investigation of chemical profile of bile acids and determination of them in cultured Bovis Calculus with UPLC-QDA (PubMed, Zhongguo Zhong Yao Za Zhi) - "The results showed that nine common bile acids, cholic acid(CA), deoxycholic acid(DCA), chenodeoxycholic acid(CDCA), taurocholic acid(TCA), taurodeoxycholic acid(TDCA), taurochenodeoxycholic acid(TCDCA), glycocholic acid(GCA), glycodeoxycholic acid(GDCA) and glycochenodeoxycholic acid(GCDCA), were founded in samples and 7 bile acids were quantified except GDCA and GCDCA...As for unconjugated bile acids, CA was the most major bile acid in cultured cow-bezoar and it was about twice as much as DCA. The relative low-cost method established in the current study is accurate, rapid and sensitive, which is suitable for the studies of other drugs from animal bile."

Journal

DIFFERENCES IN THE FECAL MICROBIOME AND METABOLOME OF PATIENTS WITH ACUTE DIARRHEA TESTED FOR CLOSTRIDIOIDES DIFFICILE INFECTION (DDW 2020) - "NAAT+/EIA- samples had higher levels of deoxycholic and taurodeoxycholic acid and lower levels of asparagine and cysteine compared to NAAT+/EIA+ samples (Figure 2)...Some discrete differences in the metabolome were found between EIA+ and EIA- groups, which suggest there might be differences in the microbiota’s metabolism among the 3 groups. These results warrant further investigation."

Clinical • Celiac Disease • Gastroenterology • Hepatology • Immunology • Inflammatory Bowel Disease

Short communication: Chemical structure, concentration, and pH are key factors influencing antimicrobial activity of conjugated bile acids against lactobacilli. (PubMed, J Dairy Sci) - "Considerable differences were observed in the antimicrobial activity between the 6 human conjugated bile acids, including glycocholic acid, taurocholic acid, glycodeoxycholic acid, taurodeoxycholic acid, glycochenodeoxycholic acid, and taurochenodeoxycholic acid...In conclusion, chemical structure, concentration, and pH are key factors influencing antimicrobial activity of conjugated bile acids against lactobacilli. This study provides theoretical guidance and technology support for developing a scientific method for evaluating the bile tolerance ability of potentially probiotic strains of lactobacilli."

Journal

A Study of HY209 in Healthy Male Volunteers for Sepsis (clinicaltrials.gov) - P1; N=40; Completed; Sponsor: Shaperon; Recruiting ➔ Completed; Trial completion date: Dec 2020 ➔ Jun 2020

Clinical • Trial completion • Trial completion date • Infectious Disease • Septic Shock

A combination of three plasma bile acids as a putative biomarker for schizophrenia. (PubMed, Acta Neuropsychiatr) - "Combination of the three BAs may be useful to diagnose schizophrenia in plasma samples."

Biomarker • Journal • CNS Disorders • Psychiatry • Schizophrenia

[VIRTUAL] CORRELATION OF BILE ACID FRACTIONS AND LIVER STRUCTURAL CHANGES IN CHILDREN WITH NON-ALCOHOLIC STEATOHEPATITIS (UEGW 2020) - "Revealed association of liver structure, bile acids content, carbohydrate metabolism features demonstrated the possibility to influence the liver fibrosis progression by bile acids ratio regulation."

Clinical • Cholestasis • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis

[VIRTUAL] RHEOLOGICAL PROPERTIES OF BILE IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS AND THYROID GLAND DYSFUNCTION (UEGW 2020) - "To evaluate the colloidal stability of the bile, the ratio of taurochenodeoxycholic acid (TCDCA) and taurodeoxycholic acid (TDCA) to taurocholic acid (TCA) and the ratio of glycochenodeoxycholic acid (GCDCA) and glycodeoxycholic acid (GDCA) to glycocholic acid (GCA) were calculated... Decreased coefficient of conjugation and hydroxylation, as well as the levels of glycoconjugates and tauroconjugates of the bile in patients with NASH combined with HT suggests the possible influence of hypothyroidism on colloidal properties of bile and thus indicates on an increased risk of gallstones formation."

Clinical • Endocrine Disorders • Genetic Disorders • Hepatology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity

[VIRTUAL] RHEOLOGICAL PROPERTIES OF BILE IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS AND THYROID GLAND DYSFUNCTION (UEGW 2020) - "To evaluate the colloidal stability of the bile, the ratio of taurochenodeoxycholic acid (TCDCA) and taurodeoxycholic acid (TDCA) to taurocholic acid (TCA) and the ratio of glycochenodeoxycholic acid (GCDCA) and glycodeoxycholic acid (GDCA) to glycocholic acid (GCA) were calculated... Decreased coefficient of conjugation and hydroxylation, as well as the levels of glycoconjugates and tauroconjugates of the bile in patients with NASH combined with HT suggests the possible influence of hypothyroidism on colloidal properties of bile and thus indicates on an increased risk of gallstones formation."

Clinical • Endocrine Disorders • Genetic Disorders • Hepatology • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity

[VIRTUAL] CORRELATION OF BILE ACID FRACTIONS AND LIVER STRUCTURAL CHANGES IN CHILDREN WITH NON-ALCOHOLIC STEATOHEPATITIS (UEGW 2020) - "Revealed association of liver structure, bile acids content, carbohydrate metabolism features demonstrated the possibility to influence the liver fibrosis progression by bile acids ratio regulation."

Clinical • Cholestasis • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis

[VIRTUAL] CORRELATION OF BILE ACID FRACTIONS AND LIVER STRUCTURAL CHANGES IN CHILDREN WITH NON-ALCOHOLIC STEATOHEPATITIS (UEGW 2020) - "Revealed association of liver structure, bile acids content, carbohydrate metabolism features demonstrated the possibility to influence the liver fibrosis progression by bile acids ratio regulation."

Clinical • Cholestasis • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis