cibinetide (ARA 290) / Araim - LARVOL DELTA

ARA290, an alternative of erythropoietin, inhibits activation of NLRP3 inflammasome in Schwann cells after sciatic nerve injury. (PubMed, Eur J Pharmacol) - "Our study further demonstrated that EPO and ARA290 inhibit the activation of NLRP3 inflammasome in Schwann cells by inhibiting NF-κB phosphorylation and reducing reactive oxygen species (ROS) production. In summary, EPO and ARA290 promote repair and regeneration by inhibiting the activation of NLRP3 inflammasome after sciatic nerve injury."

Journal • CNS Disorders • Inflammation • NLRP3

The Role of Erythropoietin in Metabolic Regulation. (PubMed, Cells) - "The non-erythroid EPOR agonist ARA290 also improves diet-induced obesity and glucose tolerance providing evidence for EPO regulation of fat metabolism independent of EPO stimulated erythropoiesis. Therefore, in addition to the primary role of EPO to stimulate erythropoiesis, EPO contributes significantly to EPOR-dependent whole-body metabolic response."

Journal • Review • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Nephrology • Obesity • Renal Disease • RUNX1

Mechanisms of ARA290 in counteracting cadmium-triggered neurotoxicity in PC12 cells. (PubMed, Toxicol Res (Camb)) - "It reduces levels of inflammation markers like TNF-α, IL-1β, and IL-6, and significantly cuts down on nerve cell death, as seen in fewer TUNEL-positive cells in experiments.A Therapeutic Promise: Overall, these findings underscore ARA290's ability to protect the nervous system through multiple pathways. This makes it a promising candidate for treating cadmium-induced nerve damage and potentially other neurodegenerative conditions."

Journal • CNS Disorders • Hematological Disorders • Inflammation • IL1B • IL6 • TNFA

COMPARATIVE EFFICACY OF MEDICAL TREATMENT EFFECTS ON PULMONARY-RELATED OUTCOMES IN PATIENTS WITH SARCOIDOSIS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS (CHEST 2024) - "For improvement in FVC, transdermal nicotine had the highest SUCRA value with a 46% probability of having the first or second rank; nicotine, chloroquine, and roflumilast had a 16%,11%, and 26% chance of being ranked first, respectively, while riociguat and bosentan were found to perform worse, even than placebo...For functional exercise capacity, as measured by 6MWT improvement, riociguat had the highest SUCRA value with a 79% probability of having the first or second rank; riociguat, infliximab 3mg/kg, and ARA 290 have a 65%, 11%, and 8% chance of being ranked best, respectively, while ustekinumab and bosentan performed worse. For chronic fatigue, as measured by FAS, melatonin had the highest SUCRA value with an 87% probability of having the first or second rank; melatonin and nicotine have a 66% and 18% of being ranked first, respectively, while methylphenidate and N-acetyl cysteine (NAC) performed worse... Transdermal nicotine (tobacco was associated with reduced..."

Retrospective data • Review • Fatigue • Immunology • Inflammation • Inflammatory Bowel Disease • Sarcoidosis

The protective effect of erythropoietin and its novel derived peptides in peripheral nerve injury. (PubMed, Int Immunopharmacol) - "The neuroprotective effects they exhibit have attracted continuous exploration of their mechanisms of action. This article will review the research on the role of EPO, ARA290 and CHBP in the nervous system around this developmental process, and provide a certain reference for the subsequent research."

Journal • Review • Inflammation

Microglial EPOR Contribute to Sevoflurane-induced Developmental Fine Motor Deficits Through Synaptic Pruning in Mice. (PubMed, Neurosci Bull) - "Together, the microglial EPOR was identified as a key mediator regulating early synaptic development in this study, which impacted sevoflurane-induced fine motor dysfunction. Moreover, ARA290 might serve as a new treatment against neurotoxicity induced by general anesthesia in clinical practice by targeting the EPO/EPOR signaling pathway."

Journal • Preclinical • Anesthesia

The Role of Macrophage Efferocytosis in the Pathogenesis of Apical Periodontitis. (PubMed, Int J Mol Sci) - "The data showed that Mφ efferocytosis is observed in the periapical tissues and enhancing the Mφ efferocytosis ability could effectively promote AP resolution via facilitating M2 Mφ polarization. Collectively, our study demonstrates the functional importance of Mφ efferocytosis in AP pathology and highlights that accelerating Mφ efferocytosis via ARA290 could serve as an adjuvant therapeutic strategy for AP."

Journal • Dental Disorders • Infectious Disease • Osteoporosis • Periodontitis

Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the β-common receptor in mice with cerebral ischemic stroke. (PubMed, CNS Neurosci Ther) - "ARA290 provided a neuroprotective effect via βCR in cerebral ischemic mice without causing erythropoiesis. This study provides novel insights into the role of ARA290 in ischemic stroke intervention."

Journal • Preclinical • Cardiovascular • CNS Disorders • Hematological Disorders • Ischemic stroke • Vascular Neurology

A small erythropoietin derived non-hematopoietic peptide reduces cardiac inflammation, attenuates age associated declines in heart function and prolongs healthspan. (PubMed, Front Cardiovasc Med) - "Finally, ARA290 preserved body weight and significantly reduced other markers of organism-wide frailty at the end of life. Administration of ARA290 reduces cell and tissue inflammation, mitigates structural and functional changes within the cardiovascular system leading to amelioration of frailty and preserved healthspan."

Journal • Cardiovascular • Fibrosis • Immunology • Inflammation • Metabolic Disorders • NFKB1 • NF-κβ

Mechanistic Approach for Protective Effect of ARA290, a Specific Ligand for the Erythropoietin/CD131 Heteroreceptor, against Cisplatin-Induced Nephrotoxicity, the Involvement of Apoptosis and Inflammation Pathways. (PubMed, Inflammation) - "Furthermore, the molecular findings indicated that gene and protein levels of TNFα, IL1β, IL6, Caspase-3, and Bax were significantly decreased and gene and protein levels of Bcl2 significantly increased in the ARA290 plus cisplatin group compared with the cisplatin group. These findings revealed that ARA290 as a potent chemo-preventive agent exerted a protective effect on cisplatin-induced nephrotoxicity mostly through its anti-apoptotic, anti-inflammatory, and antioxidant potentials and also suggested that ARA290 might be a new therapeutic approach for patients with acute kidney injury."

IO biomarker • Journal • Acute Kidney Injury • Immunology • Inflammation • Nephrology • Renal Disease • BAX • BCL2 • CASP3 • IL1B • IL6 • TNFA

Nonerythropoietic Erythropoietin Mimetic Peptide ARA290 Ameliorates Chronic Stress-Induced Depression-Like Behavior and Inflammation in Mice. (PubMed, Front Pharmacol) - "Daily administration of ARA290 during chronic stress induction in two mouse models ameliorated depression-like behavior, similar to fluoxetine. Furthermore, both drugs reversed chronic stress-induced microglia activation. Thus, ARA290 ameliorated chronic stress-induced depression-like behavior in mice through, at least partially, its anti-inflammatory effects."

Journal • Preclinical • CNS Disorders • Depression • Immunology • Inflammation • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry

"Would a peptide such as ARA-290 or Thymosin beta 4 address these tremors?" (@quijibo)

Movement Disorders • TMSB4X

Synthesis and evaluation of Tc-DOTA-ARA-290 as potential SPECT tracer for targeting cardiac ischemic region. (PubMed, Iran J Basic Med Sci) - "Biodistribution and SPECT imaging on the cardiac ischemic model showed that radiopeptide considerably accumulated in the ischemic region (cardiac ischemic-to-lung rate = 3.65 ID/g % at 0.5 hr). The results of studies, in vitro and in vivo, indicated that 99mTc-DOTA-(Lys-Dabcyl6,Phe7)-ARA-290 could be an appropriate candidate for early diagnosis of cardiac ischemia."

Journal • Cardiovascular • Coronary Artery Disease • Myocardial Infarction • Myocardial Ischemia

The Non-Erythropoietic EPO Analogue Cibinetide Inhibits Osteoclastogenesis In Vitro and Increases Bone Mineral Density in Mice. (PubMed, Int J Mol Sci) - "In addition, CIB alone or in combination with EPO inhibited osteoclastogenesis in vitro. Our findings introduce CIB either as a stand-alone treatment, or in combination with EPO, as an appealing candidate for the treatment of the bone loss that accompanies EPO treatment."

Journal • Preclinical • Hematological Disorders • Osteoporosis

The Non-Erythropoietic EPO Analogue (Cibinetide) Preserves Bone Mass in Mice (ASH 2021) - "Our findings highlight the increasing complexity of EPOR signaling in bone and pave the way for clinical translation through potential combination therapy of EPO and CIB in anemic and in cancer patients. Adjunctive administration of CIB may prevent or attenuate bone loss while preserving the erythropoietic actions of EPO. This study was supported by a grant from the Dotan Hemato-oncology Fund, the Cancer Biology Research Center, Tel Aviv University to DN and YG."

Preclinical • Hematological Disorders • Immune Modulation • Inflammation • Oncology • Osteoporosis • ITGAM

Cibinetide Protects Isolated Human Islets in a Stressful Environment and Improves Engraftment in the Perspective of Intra Portal Islet Transplantation. (PubMed, Cell Transplant) - "It improved engraftment of human islets in athymic mice. The study confirms that cibinetide is a promising agent to be used in clinical PITx."

Journal • Diabetes • Immunology • Inflammation • Metabolic Disorders • Transplantation • CASP3 • CASP7 • ITGAM

Multifaceted roles of a bioengineered nanoreactor in repressing radiation-induced lung injury. (PubMed, Biomaterials) - "Our investigations revealed that SOD@ARA290-HBc performs its radioprotective effects by protecting against radiation induced alveolar epithelial cell apoptosis and ferroptosis, suppressing oxidative stress, inhibiting inflammation and by modulating the infiltrated macrophage phenotype, or through a combination of these mechanisms. In conclusion, SOD@ARA29-HBc is a potential therapeutic agent for RILI, and given its multifaceted roles, it may be further developed as a translational nanomedicine for other related disorders."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Thoracic Cancer

fvEarly monocyte modulation by the non-erythropoietic peptide ARA 290 decelerates AD-like pathology progression. (PubMed, Brain Behav Immun) - "In aged APP/PS1 mice in which AD-like pathology is at advanced stages, ARA 290 failed to reverse Aβ pathology and to increase the levels of circulating monocytes. Our study suggests that ARA 290 early systemic treatment could prevent AD-like progression via modulation of monocyte functions by specifically increasing the ratio of patrolling monocytes."

Journal • Alzheimer's Disease • Bone Marrow Transplantation • Cardiovascular • CNS Disorders • Hematological Disorders • Immune Modulation • Immunology • Inflammation • Thrombosis • Transplantation

OM-85 in the prevention of respiratory infections: State-of-the-art and future perspectives in clinical practice. (PubMed, J Biol Regul Homeost Agents) - "The preventive use of OM-85 can reduce the use of antibiotics, contributing to contrast antibiotic resistance and saving the high cost of chronic respiratory diseases. Further studies should define the ideal candidate to OM-85 treatment."

Clinical • Journal • Chronic Obstructive Pulmonary Disease • Diabetic Nephropathy • Immunology • Infectious Disease • Nephrology • Pneumococcal Infections • Pneumonia • Pulmonary Disease • Renal Disease • Respiratory Diseases

ARA290 inhibits high glucose-induced apoptosis of NRK-52E cells. (PubMed, J Biol Regul Homeost Agents) - No abstract available

Journal • Diabetes • Diabetic Nephropathy • Nephrology • Renal Disease

The time to develop treatments for diabetic neuropathy. (PubMed, Expert Opin Investig Drugs) - "We carried out a systematic review of papers dealing with diabetic neuropathy on Pubmed in addition to a targeted Google search.Search terms included small fiber neuropathy,diffuse peripheral neuropathy, quantitative sensory testing, nerve conduction testing, intra-epidermal nerve fiber density, corneal confocal reflectance microscopy, aldose reductase inhbitors, nerve growth factor, alpha-lipoic acid, ruboxistaurin, nerve growth factor antibody, and cibinetide. Over the past half century, there have been a number of agents undergoing unsuccessful trials for treatment of DPN.There are several approved agents for relief of pain caused by diabetic neuropathy, but these do not affect the pathologic process. The failure to find treatments for diabetic neuropathy can be ascribed to (1) the complexity of design of studies and (2) the slow progression of the condition, necessitating long duration trials to prove efficacy.We propose a modification of the regulatory process to..."

Journal • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Pain • AKR1B1 • NGF

A Phase 2 Clinical Trial on the Use of Cibinetide for the Treatment of Diabetic Macular Edema. (PubMed, J Clin Med) - P2 | "The cibinetide 12-week course was safe. Improvements in NEI VFQ-25 scores, CRT, tear production, diabetic control and albuminuria, observed in some participants, warrant further investigation."

Clinical • Journal • P2 data • Diabetes • Diabetic Macular Edema • Diabetic Retinopathy • Metabolic Disorders • Ophthalmology • Renal Disease • Retinal Disorders

Araim: Commercial Update (Araim) - Anticipated expiry of patent related to composition in US in 2028

Anticipated patent expiry • Sarcoidosis

Araim Pharmaceuticals given FDA Fast Track Designation to ARA 290 for the treatment of sarcoidosis-associated small fiber neuropathy (PRNewswire) - "Araim Pharmaceuticals...announced a Fast Track Designation from the FDA for its lead compound ARA290, for treatment of Sarcoidosis-associated Small Fiber Neuropathy (SFN)....Phase 3 trials are slated to begin 4Q 2015."

Anticipated new P3 trial • Fast track designation • Pain • Sarcoidosis

US FDA grants orphan drug status to Araim Pharma's ARA 290 to treat sarcoidosis (PharmaBiz) - "The US Food and Drug Administration (FDA) has granted Orphan Drug Designation for Araim Pharmaceuticals' lead product candidate, Innate Repair Receptor activator ARA 290, for the treatment of sarcoidosis."

Orphan drug • Sarcoidosis