COG 112 / Cognosci - LARVOL DELTA

Protective Effects of COG133 on Carbon Tetrachloride-Induced Acute Liver Injury: Modulation of Inflammation, Apoptosis and Sphingolipid Metabolism. (PubMed, J Cell Mol Med) - "COG133 protects against CCl4-induced liver injury by reducing inflammation, apoptosis and morphological damage, with partial restoration of sphingolipid metabolism. These findings support its potential as a novel therapeutic agent for acute liver injury."

Journal • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Metabolic Disorders • Oncology • APOE • IL1B • NFKB1 • NOS2 • TGFB1 • TNFA

COG133 peptide-conjugated lipid nanoparticles sensitize medulloblastoma to radiation therapy in mice. (PubMed, J Control Release) - "In this study, we aimed to decrease the dose of irradiation and the proliferation of MB by using Volasertib (VSB), a Polo-like kinase 1 (PLK1) specific inhibitor. Furthermore, COG133-LNPs along with irradiation decreased tumor burden significantly as compared to VSB or radiation alone. To our observation, COG133-LNPs display high potency in killing MB cells and sensitizing them toward radiation therapy."

Journal • Preclinical • Brain Cancer • Cognitive Disorders • Developmental Disorders • Medulloblastoma • Oncology • Solid Tumor • PLK1

Engineered endolysin of Klebsiella pneumoniae phage is a potent and broad-spectrum bactericidal agent against "ESKAPEE" pathogens. (PubMed, Front Microbiol) - "Our study focuses on engineering endolysins from a Klebsiella pneumoniae phage, fusing them with ApoE23 and COG133 peptides. Our findings advance the field of endolysin engineering, facilitating the customization of these proteins to target specific bacterial pathogens. This approach holds promise for the development of personalized therapies tailored to combat ESKAPEE infections effectively."

Journal • Infectious Disease • Pneumonia

The role of ApoE in fatty acid transport from neurons to astrocytes under ischemia/hypoxia conditions. (PubMed, Mol Biol Rep) - "In conclusion, ApoE plays an important role in mediating the transport of fatty acids from neurons to astrocytes under ischemia/hypoxia conditions, and this transport mechanism is ApoE isoform dependent. ApoE4 has a low transfer efficiency and may be a potential target for the clinical treatment of neonatal hypoxic-ischemic encephalopathy."

Journal • Cardiovascular • CNS Disorders • Vascular Neurology • APOE • FABP5 • SOD1

Controlled Release of a Therapeutic Peptide in Sprayable Surgical Sealant for Prevention of Postoperative Abdominal Adhesions. (PubMed, ACS Appl Mater Interfaces) - "Two independent mouse models of cecal ligation and cecal anastomosis significantly reduced adhesion severity versus Seprafilm, COG133 liquid suspension, and no treatment control. The synergy of physical and chemical methods in a barrier material with proven preclinical studies highlights the value of COG133-loaded PLCL fiber mats in effectively dampening the formation of severe abdominal adhesions."

Journal • Fibrosis • APOE

Inhibition of APOE potentiates immune checkpoint therapy for cancer. (PubMed, Int J Biol Sci) - "Moreover, treatment by exploiting APOE inhibitor (COG 133TFA, αAPOE) was capable of curbing tumor development and fostering regression if in combination of αPD-1. Furthermore, APOE expression in cancer patients resistant to αPD-1 treatment significantly exceeded that in the sensitive group. For this reason, APOE is likely to be targeted for modifying tumor macrophage infiltrate and augmenting checkpoint immunotherapy."

IO biomarker • Journal • Dyslipidemia • Immune Modulation • Inflammation • Oncology • APOE • CCR2

Nonviral mcDNA-mediated bispecific CAR T cells kill tumor cells in an experimental mouse model of hepatocellular carcinoma. (PubMed, BMC Cancer) - "Our study suggests that it is with higher efficiency and more safety to prepare bispecific CAR T cells through non-viral mcDNA vectors. CoG133-CAR T cells have enhanced tumor-suppression capacity through dual antigen recognition and internal activation. It provides an innovative strategy for CAR T therapy of HCC, even solid tumors."

CAR T-Cell Therapy • Journal • Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD133

COG133 Attenuates the Early Brain Injury Induced by Blood-Brain Barrier Disruption in Experimental Subarachnoid Hemorrhage. (PubMed, J Healthc Eng) - "In terms of molecular mechanism, COG133 inhibits blood-brain barrier destruction through the proinflammatory CypA-NF-κB-MMP9 pathway and reduces neuronal pyroptosis by inhibiting NLRP3 inflammasome activation. In conclusion, this study demonstrated that apoE-mimetic peptide, COG133, can play a neuroprotective role by protecting blood-brain barrier function and inhibiting brain cell pyroptosis to reduce early brain injury after subarachnoid hemorrhage."

Journal • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Subarachnoid Hemorrhage • Vascular Neurology • APOE • MMP9 • NLRP3

Polymeric nanomedicine for overcoming resistance mechanisms in hedgehog and Myc-amplified medulloblastoma. (PubMed, Biomaterials) - "Moreover, systemic administration of COG-133-NPs loaded with MDB5 and SF2523 resulted in decreased tumor burden compared to non-targeted drug-loaded NPs, without any hepatic toxicity. In conclusion, our nanomedicine of MDB5 and SF2523 offers a novel therapeutic strategy to treat chemoresistant MB."

Journal • Brain Cancer • Hepatology • Medulloblastoma • Oncology • Solid Tumor • BAX • BRD4 • CCND1 • MYC • MYCN

Effect of electroacupuncture on inhibition of inflammatory response and oxidative stress through activating ApoE and Nrf2 in a mouse model of spinal cord injury. (PubMed, Brain Behav) - "These results suggest that electroacupuncture protects neurons and myelinated axons following spinal cord injury through an ApoE-dependent mechanism."

Journal • Preclinical • CNS Disorders • Inflammation • Orthopedics • APOE • PCR

Increased I2PP2A compromises TP53 function by stabilizing MDM2 in Shh medulloblastoma (AACR 2018) - "...Using COG112, a small molecule inhibitor of I2PP2A, we showed the reactivation of PP2A, concurrent with a decrease of p-MDM2 and an increase of TP53 in a time-dependent manner. From these experiments, we conclude that 1) TP53 pathway is functional in our SmoA1 mouse model; 2) I2PP2A upregulation could be the reason for rapid degradation of TP53 protein in SmoA1 mice. These findings have translational implications as they suggest that targeting I2PP2A in TP53 wild type SHH medulloblastoma patients could be a method of driving tumor cell death, thus resulting in better clinical outcomes for these patients."

Neuroendocrine Tumor

WNT / β-catenin pathway in recovering IEC-6 intestinal cells after 5-FU induced injury and treatment with mimetic peptide APOE COG133. (PubMed, Ann Oncol) - No abstract available

Journal • APOE • CTNNB1