low molecular weight dextran sulfate (ILB) / TikoMed - LARVOL DELTA

A Safety and Tolerability Study of ILB® in Patients With Amyotrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - P2 | N=11 | Terminated | Sponsor: University of Birmingham | Completed ➔ Terminated; Study initially suspended due to COVID-19 Pandemic- treatment stopped - never reopened to recruitment..

Trial termination • Amyotrophic Lateral Sclerosis • CNS Disorders

A low molecular weight dextran sulphate, ILB®, for the treatment of amyotrophic lateral sclerosis (ALS): An open-label, single-arm, single-centre, phase II trial. (PubMed, PLoS One) - P2 | "Long-term weekly ILB® injections of 2 mg/kg was well tolerated and had an acceptable safety profile in patients with ALS."

Journal • P2 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Infectious Disease • Novel Coronavirus Disease

Study to Evaluate Safety and Efficacy of IBsolvMIR in Islet Transplantation (clinicaltrials.gov) - P2 | N=7 | Terminated | Sponsor: TikoMed AB | N=18 ➔ 7 | Recruiting ➔ Terminated; Slow patient recruitment

Enrollment change • Trial termination • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Transplantation • Type 1 Diabetes Mellitus

Study to Evaluate Safety and Efficacy of IBsolvMIR in Islet Transplantation (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: TikoMed AB | Trial completion date: Feb 2024 ➔ Jun 2024 | Trial primary completion date: Dec 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Transplantation • Type 1 Diabetes Mellitus

Study to Evaluate Safety and Efficacy of IBsolvMIR in Islet Transplantation (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: TikoMed AB | Trial completion date: Jun 2023 ➔ Feb 2024 | Trial primary completion date: Mar 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Transplantation • Type 1 Diabetes Mellitus • HGF

Study to Evaluate Safety and Efficacy of IBsolvMIR in Islet Transplantation (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: TikoMed AB | Trial completion date: Feb 2022 ➔ Jun 2023 | Trial primary completion date: Feb 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Transplantation • Type 1 Diabetes Mellitus • HGF

ILB, a Low Molecular Weight Dextran Sulphate, Restores Glutamate Homeostasis, Amino Acid Metabolism and Neurocognitive Functions in a Rat Model of Severe Traumatic Brain Injury. (PubMed, Int J Mol Sci) - "These results demonstrate that ILB administration 30 min after sTBI prevents glutamate excitotoxicity and normalizes levels of amino acids involved in crucial brain metabolic functions. The ameliorations of amino acid metabolism, mitochondrial functions and energy metabolism in ILB-treated rats exposed to sTBI produced significant improvement in neurocognitive functions, reinforcing the concept that ILB is a new effective therapeutic tool for the treatment of sTBI, worth being tested in the clinical setting."

Journal • Preclinical • CNS Disorders • Psychiatry • Solid Tumor • Vascular Neurology

"TikoMed’s ILB® activates the body’s natural repair signals to restore glutamate homeostasis, amino acid metabolism and neurocognitive functions in a rat model of severe traumatic brain injury https://t.co/9b8a1hGIWb" (@CisionNews)

Preclinical • CNS Disorders • Vascular Neurology

A phase II open label clinical study of the safety, tolerability and efficacy of ILB® for Amyotrophic Lateral Sclerosis. (PubMed, PLoS One) - P=N/A | "This pilot clinical study demonstrates safety and tolerability of ILB® in patients with ALS. The exploratory biomarker and functional measures must be cautiously interpreted but suggest clinical benefit and have a bearing on the mechanism of action of ILB®. The results support the drug's potential as the first disease modifying treatment for patients with ALS."

Journal • P2 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Movement Disorders • HGF

A Safety and Tolerability Study of ILB in Patients With Amyothrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - P2; N=11; Completed; Sponsor: University of Birmingham; Active, not recruiting ➔ Completed

Clinical • Trial completion • Amyotrophic Lateral Sclerosis • CNS Disorders

ILB Attenuates Clinical Symptoms and Serum Biomarkers of Oxidative/Nitrosative Stress and Mitochondrial Dysfunction in Patients with Amyotrophic Lateral Sclerosis. (PubMed, J Pers Med) - P=N/A | "A significant normalization of the serum levels of several key metabolites was observed over the treatment period, including N-acetylaspartate (NAA), oxypurines, biomarkers of oxidative/nitrosative stress and antioxidants. An improved serum metabolic profile was accompanied by significant amelioration of the patients' clinical conditions, indicating a response to ILB treatment that appears to be mediated by improvement of tissue bioenergetics, decrease of oxidative/nitrosative stress and attenuation of (neuro)inflammatory processes."

Biomarker • Clinical • Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Metabolic Disorders

Tikomed’s ILB attenuates clinical symptoms and serum biomarkers of oxidative/nitrosative stress and mitochondrial dysfunction in ALS patients, data published by the Journal of Personalized Medicine (PRNewswire) - P2, N=13; NCT03613571; Sponsor: TikoMed; "The data revealed a significant normalization of the serum levels of several key metabolites in addition to a significant improvement of patients' clinical conditions for the duration of the ILB® treatment period. The treatment response appears to be mediated by improvement of tissue bioenergetics, decrease of oxidative/nitrosative stress and attenuation of (neuro)inflammatory processes."

P2 data • Amyotrophic Lateral Sclerosis • CNS Disorders

A Safety and Tolerability Study of ILB in Patients With Amyothrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - P2; N=11; Active, not recruiting; Sponsor: University of Birmingham; Trial completion date: May 2021 ➔ Aug 2021; Trial primary completion date: Apr 2021 ➔ Aug 2021

Clinical • Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders • Complement-mediated Rare Disorders

Study to Evaluate Safety and Efficacy of IBsolvMIR in Islet Transplantation (clinicaltrials.gov) - P2; N=18; Recruiting; Sponsor: TikoMed AB; Trial completion date: Oct 2021 ➔ Feb 2022; Trial primary completion date: Oct 2021 ➔ Feb 2022; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Transplantation • Type 1 Diabetes Mellitus

A Safety and Tolerability Study of ILB in Patients With Amyothrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - P2; N=11; Active, not recruiting; Sponsor: University of Birmingham; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Amyotrophic Lateral Sclerosis • CNS Disorders • Complement-mediated Rare Disorders

Prevention of dextran sulfate sodium-induced mouse colitis by the fungal protein Ling Zhi-8 via promoting the barrier function of intestinal epithelial cells. (PubMed, Food Funct) - "These results indicated that LZ-8 protected the barrier function of IECs against inflammation. Thus, LZ-8 may potentially be a novel candidate for treating inflammatory bowel disease (IBD)."

Journal • Gastroenterology • Gastrointestinal Disorder • Immune Modulation • Immunology • Inflammation • Inflammatory Bowel Disease • Oncology

The possible mechanism of the protective effect of a sulfated polysaccharide from Gracilaria Lemaneiformis against colitis induced by dextran sulfate sodium in mice. (PubMed, Food Chem Toxicol) - "Therefore, SP could alleviate DSS-induced colitis via enhancing intestinal barrier, reducing inflammation, activating SCFA receptors and regulating gut microbiota. It could be developed as functional foods which is good for gut health."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • CLDN1 • IL1B • IL6 • MUC2 • TNFA

5-Aminosalicylic Acid Ameliorates Colitis and Checks Dysbiotic Escherichia coli Expansion by Activating PPAR-γ Signaling in the Intestinal Epithelium. (PubMed, mBio) - "Here, we show that 5-ASA ameliorates colitis in dextran sulfate sodium (DSS)-treated mice by activating PPAR-γ signaling in the intestinal epithelium...Activation of epithelial peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling with 5-aminosalicylic acid (5-ASA) was sufficient to restore mitochondrial activity and blunt a dysbiotic E. coli expansion. These data identify the host's epithelial metabolism as a potential treatment target to remediate microbial signatures of dysbiosis, such as a dysbiotic E. coli expansion in the fecal microbiota."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • PPARG

Aberrant SLC6A14 Expression Promotes Proliferation and Metastasis of Colorectal Cancer via Enhancing the JAK2/STAT3 Pathway. (PubMed, Onco Targets Ther) - "Besides, azoxymethane/dextran sulfate sodium salt (AOM/DSS)-induced CRC and tumor xenograft models were constructed to explore the effects of SLC6A14 blockade or overexpression during tumor progression in vivo...Besides, two different animal studies verified the tumor-promoting effect of SLC6A14 in CRC. Our data illustrated the crucial function of SLC6A14 during CRC progression, suggesting SLC6A14/JAK2/STAT3 axis may serve as novel therapeutic targets for patients with CRC."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PCR • SLC6A14

Function of intestinal barrier protected by regulating the miR-199a-3p in Ulcerative Colitis: Modulation of IL-23/IL-17A axis. (PubMed, Fundam Clin Pharmacol) - "Ulcerative colitis was induced by administration of dextran sulfate sodium [DSS (3%)] with drinking water for the duration of one week in mice and miR-199a-3p oligomer was treated for the same duration...The level of Th17 in the serum and mRNA expression of TGFβ, Foxp3, RORγt and STAT3 was attenuated in miR-199a-3p oligomer treated UC mice. In conclusion, the data of the study suggest that treatment with miR-199a-3p oligomer ameliorates intestinal barrier in ulcerative colitis by down regulating the IL-17A/IL-23 axis."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Stress Ulcer • Ulcerative Colitis • FOXP3 • IL17A • MIR199A1 • STAT3

Enzymatically-inactive Tissue-type Plasminogen Activator Reverses Disease Progression in the Dextran Sulfate Sodium Mouse Model of Inflammatory Bowel Disease. (PubMed, Am J Pathol) - "Mesenchymal cells that line intestinal crypts and provide barrier function expressed LRP1 and thus, represent another potential target for EI-tPA. These results demonstrate that the NMDA-R/LRP1 receptor system may be a target for drug development in diseases characterized by tissue damage and chronic inflammation."

Journal • Preclinical • Developmental Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • PTPRC

Enhanced IL-36R signaling promotes barrier impairment and inflammation in skin and intestine. (PubMed, Sci Immunol) - "Humanized DITRA-like mice displayed increased skin inflammation in a preclinical model of psoriasis, and in vivo blockade of IL-36R pathway using anti-human IL-36R antibody ameliorated imiquimod-induced skin pathology as both prophylactic and therapeutic treatments. Deeper characterization of the humanized DITRA-like mice revealed that deregulated IL-36R signaling promoted tissue pathology during intestinal injury and led to impairment in mucosal restoration in the repair phase of chronic dextran sulfate sodium (DSS)-induced colitis. Blockade of IL-36R pathway significantly ameliorated DSS-induced intestinal inflammation and rescued the inability of DITRA-like mice to recover from mucosal damage in vivo. Our results indicate a central role for IL-36 in regulating proinflammatory responses in the skin and epithelial barrier function in the intestine, suggesting a new therapeutic potential for targeting the IL-36R axis in psoriasis and at the later stages of intestinal..."

Journal • Dermatitis • Dermatology • Dermatopathology • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Psoriasis

Pomegranate peel attenuates dextran sulfate sodium-induced lipid peroxidation in rat small intestine by enhancing the glutathione/glutathione disulfide redox potential. (PubMed, J Sci Food Agric) - "This study demonstrates that PP protects the small intestine against DSS-induced lipid peroxidation by enhancing the GSH/GSSG redox potential. Powdered PP is a promising agricultural by-product containing a mixture of bioactive polyphenols that can be used for the production of functional foods aimed at the prevention of oxidative stress-induced small intestine pathogenesis."

Journal

Efficient treatment of a preclinical inflammatory bowel disease model with engineered bacteria. (PubMed, Mol Ther Methods Clin Dev) - "The expression levels of TNF and other cytokines significantly decreased upon this treatment in dextran sulfate sodium (DSS)-induced colitis, and the degree of inflammation was significantly reduced. With further safety modifications this method could serve as a safe and side effect-free alternative to biologicals targeting TNF or other inflammatory mediators."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • PRF1 • TNFA

Galanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model. (PubMed, Sci Rep) - "After colitis induction with 2% dextran sulfate sodium (DSS) for 7 days, mice lacking GALR (GALR-KO) lost more body weight, exhibited more severe colonic inflammation and aggravated histologic damage, with increased infiltration of neutrophils compared to wild-type animals...In conclusion, granulocyte GALR and GALR expression is related to IBD activity in humans, and DSS-induced colitis in mice is strongly affected by GALR loss. Consequently, GALR poses a novel therapeutic target for IBD."

Journal • Preclinical • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis