bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2024.06.05.597513

Preclinical study of the human recombinant Erythropoietin (GBPD002) compared with Eprex

Nag, K.·Mohiuddin, M.·Khan, M. M. R.·Kumar, S.·Sarker, M. E. H.·Roy, R.·Biswas, B. K.·Barman, U.·Sultana, N.·Bachar, S. C.·Haq, S. R.
View original source ↗Export metadata ↓

Abstract

Erythropoietin (EPO) is a glycoprotein that an essential growth factor for erythroid progenitors at the bone marrow, which appears in blood as a response to hypoxia. It is produced mainly by the kidneys; and its biosynthesis and release are stimulated by the reduction of tissue oxygenation and/or the reduction of the mass of erythrocytes. Here, we report the results of the preclinical evaluation of the safety of GBPD002 a recombinant human erythropoietin (rhEPO) developed by the Globe Biotech Limited, Bangladesh, through a comparative study of acute toxicity with Eprex(R), a commercial homologue from Janssen, UK. The product was administered subcutaneously into Wistar rats, at 500 lU/kg of therapeutic dose (TD) and 3 times of TD for the single dose toxicity study on 14 consecutive days and 125 UL/kg, 250 UL/kg, 500 UL/kg, 750 UL/kg, 1000 UL/kg, 1250 UL/kg and 1500 UL/kg of GBPD002 and Eprex(R) on 7 consecutive days respectively for the repeated dose toxicity study. Hematological and biochemical parameters were measured for all test subjects before first dose injection and the day after last dose injection of the both studies. Necropsy and histopathology of representative subjects from each group were also observed to find any pathological significance like degeneration or cellular necrosis in internal organs such as kidney, liver, lung and spleen of any rat under experiment. Both GBPD002 and Eprex(R) comparative toxicology studies revealed similar pharmacologically driven mechanisms of toxicity, which is statistically insignificant (p >0.05). Though hematology parameter values stayed within the normal range during the assay period but the high count of hemoglobin and high hematocrit (P<0.05), together with the decrease in white blood cell, confirm the therapeutic effect of Erythropoietin in both studies. Moreover, in both studies, the initial and final values of aspartate aminotransferase, alanine aminotransferase and blood urea nitrogen were also found similar (p >0.05) for both GBPD002 and Eprex(R) in the study. The study clearly established that the toxicological profile of "GBPD002" and Eprex(R), administered subcutaneously, were similar and related to the known pharmacology of erythropoietin alfa; hereby, demonstrating the proof of totality and no residual uncertainty between "GBPD002" and Eprex(R). Therefore, "GBPD002" and Eprex(R) shall be administered interchangeably in relevant indications.

Explore related subjects

pharmacology and toxicologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Nag, K., Mohiuddin, M., Khan, M. M. R., Kumar, S., Sarker, M. E. H., Roy, R., Biswas, B. K., Barman, U., Sultana, N., Bachar, S. C., Haq, S. R.. 2024-06-06. Preclinical study of the human recombinant Erythropoietin (GBPD002) compared with Eprex. https://doi.org/10.1101/2024.06.05.597513

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

PCB-Exposed Gut Microbiota Recapitulate Neurobehavioral Deficits and Reprogram Hippocampal Transcriptomic Signatures

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants associated with developmental neurotoxicity and autism spectrum disorder (ASD). However, whether PCB-induced alterations in gut microbiota contribute to neurodevelopmental toxicity independently of direct chemical exposure remains unclear. Here, we investigated whether transplantation of PCB-associated gut microbiota produces early neurobehavioral alterations and disrupts brain molecular pathways in offspring. Gut microbiota from conventional dams exposed to the Fox River PCB mixture (FRM; 6.0 mg/kg/day) or vehicle were transplanted into germ-free recipient females without direct PCB administration. At postnatal day 7 (P7), offspring underwent ultrasonic vocalization (USV) testing, whole-brain RNA sequencing (n = 4/sex/group), and untargeted serum metabolomics. Untargeted serum metabolomics were also performed in donor dams. PCB-associated fecal microbiota transplantation (FMT) significantly reduced offspring USVs, reproducing effects observed following direct maternal PCB exposure. Brain transcriptomics in offspring identified substantially more differentially expressed genes in males (9,339) than females (1,082), including 512 shared genes. Concordantly regulated genes revealed downregulation of neurotransmitter signaling and ion channel pathways alongside upregulation of RNA processing pathways. Male-associated responses involved altered protein synthesis and neuronal signaling, whereas female-associated responses involved DNA repair and extracellular matrix remodeling. Despite these molecular differences, behavioral responses showed no significant sex-dependent effect. Maternal metabolomics revealed increased bile acids and decreased indole-3-propionic acid, highlighting potential AhR-NF{kappa}B and bile acid-associated signaling mechanisms. Offspring metabolomics further identified alterations in lipid-associated metabolites and metabolic profiles. Collectively, these findings show that transferring PCB-exposed microbiota reproduces early neurobehavioral alterations and induces shared and sex-biased molecular responses, identifying the maternal gut microbiome as a candidate mediator linking PCB exposure to developmental neurotoxicity.

pharmacology and toxicology↗
bioRxiv2026

Cisplatin-triggered sensory dysfunction in NER-defective C. elegans involves GABAergic and cholinergic signaling

Cisplatin (CisPt) is a widely used anticancer drug that causes neurotoxicity as a dose-limiting adverse effect. DNA damage contributes to CisPt-induced neurotoxicity, yet the molecular mechanisms involved remain unclear. Here, we aim to identify pathophysiological mechanisms contributing to DNA damage-driven development of sensory neuronal dysfunction using the 3R-compliant model organism Caenorhabditis elegans. To this end, we employed the nucleotide excision repair (NER)-deficient ercc-1 mutant, which shows enhanced CisPt-induced sensory dysfunction as monitored by the chemotaxis assay, to elucidate drug-induced alterations in neurotransmission and transcriptome. We found that CisPt reduces gamma-aminobutyric acid (GABA) levels in the nematode and that GABA supplementation rescues ercc-1 mutants from CisPt-evoked sensory neurotoxicity, pointing to a neuroprotective function of GABA in the context of our study. Moreover, CisPt impairs the morphological integrity of GABAergic neurons particularly in ercc-1 mutants, which again is rescued by GABA substitution. Conversely, the cholinergic agonist carbachol impairs sensory function and exacerbates the neurotoxic effects of CisPt in ercc-1 mutants, indicating detrimental effects resulting from cholinergic excitation. Transcriptome analysis revealed that CisPt treatment stimulates a broard transcriptional response, including pathways involved in the regulation of neuronal communication, including acetylcholine-mediated neurotransmission, with pronounced effects occurring in the absence of ERCC-1. Based on these finding we suggest impaired GABAergic signaling and the loss of neuronal integrity GABAergic neurons as well as excessive cholinergic excitation as key mechanisms linking CisPt-induced DNA damage in NER defective nematodes to sensory dysfunction. Hence, targeting the balance between GABAergic inhibition and cholinergic excitation is suggested to counteract sensory neurotoxicity triggered by CisPt.

pharmacology and toxicology↗
bioRxiv2026

Mathematical model of phenotypic plasticity predicts interconversion is a drug target for neuroblastoma.

Neuroblastoma is a paediatric cancer arising from the sympathetic nervous system as neural crest cells, made up of noradrenergic (NOR/ADRN/N), mesenchymal like (MES/S), and intermediate (I-type/I) cell types. These cells can interconvert between types, contributing to treatment resistance and relapse. We developed a mathematical model to investigate how interconversion patterns affect the efficacy of phenotype-specific inhibitors. We used three ordinary differential equations to describe the dynamics of the three populations, including logistic growth, interconversion, and drug-induced death. Of the 64 possible interconversion patterns, five reduced the target population: two for N cells and three for S cells. N targeting patterns were more effective with higher interconversion rates, while mesenchymal targeting patterns were more effective with lower interconversion rates. Stability analysis revealed that natural tumour growth was always unstable, but during treatment, N-suppressing patterns combined with an S inhibitor gave the most consistently stable origin. Testing multi-stage and cyclic treatment schedules revealed that N-suppressing patterns with an S inhibitor, followed by an S-suppressing pattern with an N inhibitor, achieved more reliable remission. Three of the five patterns of interest correspond to reported biological plausibility, and known compounds exist to induce most of the required transitions, supporting the clinical relevance of these strategies for improving neuroblastoma treatment outcomes.

pharmacology and toxicology↗