Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
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| metabolism and pharmacokinetics of a potent n-acylindole antagonist of the oxe receptor for the eosinophil chemoattractant 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ete) in rats and monkeys. | we previously identified the indole 264 as a potent in vitro antagonist of the human oxe receptor that mediates the actions of the powerful eosinophil chemoattractant 5-oxo-ete. no antagonists of this receptor are currently commercially available or are being tested in clinical studies. the lack of a rodent ortholog of the oxe receptor has hampered progress in this area because of the unavailability of commonly used mouse or rat animal models. in the present study, we examined the feasibility of ... | 2018 | 29339225 |
| technique for orthotopic liver transplantation in cynomolgus monkeys (macaca fascicularis). | recent studies investigating new strategies to modulate the immune system have utilized animal models of liver transplantation (lt). however, the anhepatic phase (ahp) remains a crucial problem in lt. the aim of the present study is to introduce a technique for successful orthotopic lt in cynomolgus monkeys using an early-reperfusion strategy. | 2018 | 29333420 |
| non-destructive determination of muscle architectural variables through the use of dicect. | the fascicular architecture of skeletal muscle dictates functional parameters such as force production and contractile velocity. muscle microarchitecture is typically determined by means of manual dissection, a technique that is inherently destructive to specimens. furthermore, fascicle lengths and pennation angles are commonly assessed at only a limited number of sampling sites per muscle. we present the results of a digital technique to non-destructively assess muscle architectural variables f ... | 2018 | 29330959 |
| sustained plasma hepcidin suppression and iron elevation by anticalin-derived hepcidin antagonist in cynomolgus monkey. | anaemia of chronic disease (acd) has been linked to iron-restricted erythropoiesis imposed by high circulating levels of hepcidin, a 25 amino acid hepatocyte-derived peptide that controls systemic iron homeostasis. here, we report the engineering of the human lipocalin-derived, small protein-based anticalin prs-080 hepcidin antagonist with high affinity and selectivity. | 2018 | 29329501 |
| generation of a precise oct4-hrgfp knockin cynomolgus monkey model via crispr/cas9-assisted homologous recombination. | 2018 | 29327727 | |
| generation of knock-in cynomolgus monkey via crispr/cas9 editing. | 2018 | 29327726 | |
| brain structural changes in cynomolgus monkeys administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: a longitudinal voxel-based morphometry and diffusion tensor imaging study. | in animal models of parkinson's disease (pd), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (mptp) is one of the most widely used agents that damages the nigrostriatal dopaminergic pathway. however, brain structural changes in response to mptp remain unclear. this study aimed to investigate in vivo longitudinal changes in gray matter (gm) volume and white matter (wm) microstructure in primate models administered with mptp. in six cynomolgus monkeys, high-resolution magnetic resonance imaging (mri ... | 2018 | 29320500 |
| selective cd28 inhibition modulates alloimmunity and cardiac allograft vasculopathy in anti-cd154-treated monkeys. | selective cd28 inhibition is actively pursued as an alternative to b7 blockade using cytotoxic t lymphocyte antigen 4 ig based on the hypothesis that the checkpoint immune regulators cytotoxic t lymphocyte antigen 4 and programmed death ligand 1 will induce tolerogenic immune signals. we previously showed that blocking cd28 using a monovalent nonactivating reagent (single-chain anti-cd28 fv fragment linked to alpha-1 antitrypsin [sc28at]) synergizes with calcineurin inhibitors in nonhuman primat ... | 2018 | 29319621 |
| usefulness of simultaneous and sequential monitoring of glucose level and electrocardiogram in monkeys treated with gatifloxacin under conscious and nonrestricted conditions. | drug-induced cardiac electrophysiological abnormalities accompanied by hypoglycemia or hyperglycemia increase the risk for life-threatening arrhythmia. to assess the drug-induced cardiotoxic potential associated with extraordinary blood glucose (glu) levels, the effect of gatifloxacin (gflx) which was frequently associated with glu abnormality and qt/qtc prolongations in the clinic on blood glu and electrocardiogram (ecg) parameters was investigated in cynomolgus monkeys (n=4) given gflx orally ... | 2018 | 29311442 |
| dual blockade of interleukin-1β and interleukin-17a reduces murine arthritis pathogenesis but also leads to spontaneous skin infections in nonhuman primates. | despite the efficacy of biologics for treatment of rheumatoid arthritis (ra), many patients show inadequate responses and likely require neutralization of multiple mediators. neutralization of both interleukin (il)-1β and il-17a with monoclonal antibodies showed greater efficacy than either agent alone in a mouse arthritis model with cooperative inhibition of key inflammatory factors, il-6, granulocyte colony-stimulating factor (g-csf), and cxc chemokine ligand (cxcl)1. given the potential clini ... | 2018 | 29311111 |
| proprioceptive changes in bilateral knee joints following unilateral anterior cruciate ligament injury in cynomolgus monkeys. | background the anterior cruciate ligament (acl) is one of the most important structures maintaining stability of knee joints, and the proprioception of the acl plays a key role in it. if the acl is injured in the unilateral knee joint, it changes nerve electrophysiology, morphology, and quantity of the proprioceptors in the bilateral acl. the aim of this study was to explore the proprioceptive changes in the bilateral knee joints following unilateral acl injury, and to provide a theoretical foun ... | 2018 | 29305572 |
| long-term nonhuman primate renal allograft survival without ongoing immunosuppression in recipients of delayed donor bone marrow transplantation. | we have previously reported successful induction of renal allograft tolerance in nonhuman primates (nhp) after an initial posttransplant period of conventional immunosuppression (delayed tolerance) using a nonmyeloablative conditioning regimen consisting of anti-cd154 and anti-cd8 mabs plus equine antithymocyte globulin (atgam) and donor bone marrow transplantation (dbmt). because these reagents are not currently clinically available, the protocol was revised to be applicable to human recipients ... | 2018 | 29300231 |
| adct-402, a pbd dimer-containing antibody drug conjugate targeting cd19-expressing malignancies. | human cd19 antigen is a 95-kda type i membrane glycoprotein in the immunoglobulin superfamily whose expression is limited to the various stages of b-cell development and differentiation and is maintained in the majority of b-cell malignancies, including leukemias and non-hodgkin lymphomas of b-cell origin. coupled with its differential and favorable expression profile, cd19 has rapid internalization kinetics and is not shed into the circulation, making it an ideal target for the development of a ... | 2018 | 29298756 |
| an antigen-free, plasmacytoid dendritic cell-targeting immunotherapy to bolster memory cd8+ t cells in nonhuman primates. | the priming, boosting, and restoration of memory cytotoxic cd8+ t lymphocytes by vaccination or immunotherapy in vivo is an area of active research. particularly, nucleic acid-based compounds have attracted attention due to their ability to elicit strong ag-specific ctl responses as a vaccine adjuvant. nucleic acid-based compounds have been shown to act as anticancer monotherapeutic agents even without coadministration of cancer ag(s); however, so far they have lacked efficacy in clinical trials ... | 2018 | 29431693 |
| metabolite identification of the antimalarial naphthoquine using liquid chromatography-tandem high-resolution mass spectrometry in combination with multiple data-mining tools. | naphthoquine (nq) is one of important partner drugs of artemisinin-based combination therapy (act), which is recommended for the treatment of uncomplicated plasmodium falciparum. nq shows a high cure rate after a single oral administration. it is absorbed quickly (time to peak concentration 2-4 h) and has a long elimination half-life (255 h). however, the metabolism of nq has not been clarified. in this work, the metabolite profiling of nq was studied in six liver microsomal incubates (human, cy ... | 2018 | 29430676 |
| a cross-species comparison of abnormal behavior in three species of singly-housed old world monkeys. | abnormal behavior occurs in a number of captive nonhuman primate species and is often used as an indicator of welfare. however, reported levels of abnormal behavior often vary across species, making general welfare judgments difficult. the purpose of this study was to assess differences in levels of abnormal behavior and associated risk factors across three species of old world monkeys in order to identify similarities and differences across species. the subjects were 415 (109 females) cynomolgu ... | 2018 | 29422700 |
| inotropic effects of nicorandil on cardiac contractility assessed by left ventricular pressure-volume relationship analyses in anesthetized monkeys. | nicorandil is a representative antianginal drug that has dual properties of a nitrate and adenosine triphosphate-sensitive potassium (katp) channel agonist; however, its effects on integrated cardiac function have not been fully understood. this study was conducted to clarify the functional, hemodynamic, and electrophysiological effects of nicorandil using ventricular pressure-volume loop analysis in isoflurane-anesthetized monkeys. nicorandil was given intravenously at therapeutic doses of 0.2 ... | 2018 | 29420355 |
| rna-seq analysis of the transcriptome of the liver of cynomolgus monkeys with type 2 diabetes. | genetic and environmental factors such as high-fat diet are involved in the development of type 2 diabetes mellitus (t2dm). cynomolgus monkey shares similar genetic makeup, tissue structures, physiology and metabolic function to human. this study aimed to establish t2dm model in cynomolgus monkey and compare expression profiles of hepatic genes and their associated pathways in normal cynomolgus monkeys and those with t2dm. we employed rna-seq technique and identified 1451 differentially expresse ... | 2018 | 29414690 |
| discovery of a cynomolgus monkey family with retinitis pigmentosa. | to accelerate the development of new therapies, an inherited retinal degeneration model in a nonhuman primate would be useful to confirm the efficacy in preclinical studies. in this study, we describe the discovery of retinitis pigmentosa in a cynomolgus monkey (macaca fascicularis) pedigree. | 2018 | 29411010 |
| in vivo characterization of two 18f-labeled pde10a pet radioligands in nonhuman primate brains. | positron emission tomography (pet) with phosphodiesterase 10a (pde10a) specific radioligands provides a noninvasive and quantitative imaging tool to access the expression of this enzyme in vivo under normal and diseased conditions. we recently reported two potent 18f-labeled pde10a radioligands (18f-tz19106b and 18f-tz8110); initial evaluation in rats and nonhuman primates indicated stable metabolic profiles and excellent target-to-nontarget ratio (striatum/cerebellum) for both tracers. herein, ... | 2018 | 29400443 |
| a case report of spontaneous staphylococcal meningitis in a cynomolgus monkey. | this report describes a suppurative meningitis in a young cynomolgus. the animal had neutrophil aggregation in the subarachnoid space and hemorrhage in bilateral adrenal glands. staphylococcus was identified by fish in brain. to our knowledge, this is the first case of staphylococcal meningitis with waterhouse-friderichsen syndrome in a cynomolgus monkey. | 2018 | 29399828 |
| cloning of macaque monkeys by somatic cell nuclear transfer. | generation of genetically uniform non-human primates may help to establish animal models for primate biology and biomedical research. in this study, we have successfully cloned cynomolgus monkeys (macaca fascicularis) by somatic cell nuclear transfer (scnt). we found that injection of h3k9me3 demethylase kdm4d mrna and treatment with histone deacetylase inhibitor trichostatin a at one-cell stage following scnt greatly improved blastocyst development and pregnancy rate of transplanted scnt embryo ... | 2018 | 29395327 |
| labyrinthitis ossificans in a cynomolgus macaque (macaca fascicularis). | labyrinthitis is inflammation of the membranous and bony labyrinth of the inner ear. typical portals of entry includehematogenous spread from the cochlear vasculature, passage of otitis media pathogens through the round window, and mostcommonly, meningogenic spread from the subarachnoid space. the sequela of chronic inner ear inflammation is labyrinthitisossificans, in which inner ear structures are replaced by fibrous and osseous tissues. labyrinthitis in humans has been reportedconcurrently wi ... | 2018 | 29650059 |
| in vitro-in vivo extrapolation of oatp1b-mediated drug-drug interactions in cynomolgus monkey. | hepatic organic anion-transporting polypeptides (oatp) 1b1 and 1b3 are clinically relevant transporters associated with significant drug-drug interactions (ddis) and safety concerns. given that oatp1bs in cynomolgus monkey share >90% degree of gene and amino acid sequence homology with human orthologs, we evaluated the in vitro-in vivo translation of oatp1b-mediated ddi risk using this preclinical model. in vitro studies using plated cynomolgus monkey hepatocytes showed active uptake km values o ... | 2018 | 29643253 |
| [shaoyangzhugu formula regulates p19arf-p53-p21cip1 signaling pathway to ameliorate cartilage degeneration in aged cynomolgus monkeys with knee osteoarthritis]. | to study the effect of shaoyangzhugu (syzg) formula (a formula consisting of 9 traditional chinese drugs) in delaying the degeneration of articular cartilage and the role p19arf-p53-p21cip1 signaling pathway in mediating this effect. | 2018 | 29643043 |
| comparative study of three xenic media culture for cultivation of balantidium coli strains. | the aim of the present study was to evaluate the growth rate of balantidium coli in three xenic media cultures. between 2013 and 2015, 10 b. coli isolates obtained from feces of cynomolgus macaques, and 30 isolates from feces of pigs were studied. an inoculum of 500 trophozoites was transferred to tubes containing les, tysgm-9 and pavlova media. these cultures were evaluated at incubation times of 24, 48, 72 and 96 hours. in most of strains analyzed wasn't showed significant difference in the gr ... | 2018 | 29641791 |
| malaria parasites of long-tailed macaques in sarawak, malaysian borneo: a novel species and demographic and evolutionary histories. | non-human primates have long been identified to harbour different species of plasmodium. long-tailed macaques (macaca fascicularis), in particular, are reservoirs for p. knowlesi, p. inui, p. cynomolgi, p. coatneyi and p. fieldi. a previous study conducted in sarawak, malaysian borneo, however revealed that long-tailed macaques could potentially harbour novel species of plasmodium based on sequences of small subunit ribosomal rna and circumsporozoite genes. to further validate this finding, the ... | 2018 | 29636003 |
| linear pharmacokinetic parameters for monoclonal antibodies are similar within a species and across different pharmacological targets: a comparison between human, cynomolgus monkey and hfcrn tg32 transgenic mouse using a population-modeling approach. | the linear pharmacokinetics (pk) of therapeutic monoclonal antibodies (mabs) can be considered a class property with values that are similar to endogenous igg. knowledge of these parameters across species could be used to avoid unnecessary in vivo pk studies and to enable early pk predictions and pharmacokinetic/pharmacodynamic (pk/pd) simulations. in this work, population-pharmacokinetic (poppk) modeling was used to determine a single set of 'typical' poppk parameters describing the linear pk o ... | 2018 | 29634430 |
| a cynomolgus macaque model for crimean-congo haemorrhagic fever. | crimean-congo haemorrhagic fever (cchf) is the most medically significant tick-borne disease, being widespread in the middle east, asia, africa and parts of europe 1 . increasing case numbers, westerly movement and broadly ranging case fatality rates substantiate the concern of cchf as a public health threat. ixodid ticks of the genus hyalomma are the vector for cchf virus (cchfv), an arbovirus in the genus orthonairovirus of the family nairoviridae. cchfv naturally infects numerous wild and dom ... | 2018 | 29632370 |
| an anatomic characterization of the midbrain near response neurons in the macaque monkey. | these experiments were designed to reveal the location of the premotor neurons that have previously been designated physiologically as the midbrain near response cells controlling vergence, lens accommodation, and pupillary constriction in response to target distance. | 2018 | 29625471 |
| hypothetical endogenous siv-like antigens in mauritian cynomolgus macaques. | simian immunodeficiency virus (siv) infection of mauritian cynomolgus macaques (mcms) is an increasingly important nonhuman primate model for hiv vaccine research. we previously reported that in mcms anti-siv antibodies can be naturally developed without exogenous infection or vaccination, and that a vaccine targeting siv protease cleavage sites (pcs) can cross-induce antibodies to non-pcs siv antigens. we speculate that this is potentially caused by the existence of endogenous siv-like antigens ... | 2018 | 29618899 |
| fgf21 acts as a negative regulator of bile acid synthesis. | fibroblast growth factor 21 (fgf21) is a potent regulator of glucose and lipid homeostasis in vivo; its most closely related subfamily member, fgf19, is known to be a critical negative regulator of bile acid synthesis. to delineate whether fgf21 also plays a functional role in bile acid metabolism, we evaluated the effects of short- and long-term exposure to native fgf21 and long-acting fgf21 analogs on hepatic signal transduction, gene expression and enterohepatic bile acid levels in primary he ... | 2018 | 29615519 |
| refinement of in vitro methods for identification of aldehyde oxidase substrates reveals metabolites of kinase inhibitors. | to identify aldehyde oxidase (ao) substrates, an assay procedure was developed that leverages the capabilities of high-resolution mass spectrometry to simultaneously monitor parent loss and formation of hydroxylated metabolite over time in incubations with liver cytosol. by incorporating metabolite monitoring, false positives resulting from metabolism by other cytosolic enzymes or processes were decreased. a diverse set of 34 kinase inhibitors containing ao-substrate motifs was screened, and 35% ... | 2018 | 29615437 |
| a novel selective soluble guanylate cyclase activator, mgv354, lowers intraocular pressure in preclinical models, following topical ocular dosing. | the nitric oxide/soluble guanylate cyclase/protein kinase g (no/sgc/pkg) is known to be involved in the regulation of intraocular pressure (iop) and may be dysregulated in glaucoma. the purpose is to demonstrate that the sgc activator mgv354 lowers iop in a monkey model of glaucoma and could be considered as a possible new clinical drug candidate. | 2018 | 29610853 |
| pre-clinical and translational pharmacology of a human interleukin-22 igg fusion protein for potential treatment of infectious or inflammatory diseases. | interleukin (il)-22 plays protective roles in infections and in inflammatory diseases that have been linked to its meditation of innate immunity via multiple mechanisms. il-22 binds specifically to its heterodimeric receptor, which is expressed on a variety of epithelial tissues. uttr1147a is a recombinant fusion protein that links the human cytokine il-22 with the fc portion of human immunoglobulin (ig) g4. here, we report extensive in vitro and in vivo nonclinical studies that were conducted t ... | 2018 | 29608910 |
| surgical removal of internal limiting membrane and layering of aav vector on the retina under air enhances gene transfection in a nonhuman primate. | to determine if the surgical removal of the internal limiting membrane (ilm) in nonhuman primates (nhps) will result in safe and effective transfection of adeno-associated viral (aav2) vectors using green fluorescent protein (gfp) as a reporter. | 2018 | 30025098 |
| serotonin concentration enhancers at clinically relevant doses reduce [11c]az10419369 binding to the 5-ht1b receptors in the nonhuman primate brain. | the serotonin (5-ht) system plays an important role in the pathophysiology and treatment of several major psychiatric disorders. currently, no suitable positron emission tomography (pet) imaging paradigm is available to assess 5-ht release in the living human brain. [11c]az10419369 binds to 5-ht1b receptors and is one of the most 5-ht-sensitive radioligands available. this study applied 5-ht concentration enhancers which can be safely studied in humans, and examined their effect on [11c]az104193 ... | 2018 | 30013068 |
| artificial liver and renal support system for cynomolgus monkeys with surgery-induced acute renal failure: a preclinical study. | renal dysfunction is one of the most common complications of liver cirrhosis and is associated with increased morbidity and mortality. however, no available technology can simultaneously support liver and renal function in these patients. the aim of this study was to evaluate the safety and efficacy of an artificial liver and renal support system in cynomolgus monkeys with surgery-induced arf. the arf model was established by ligature of bilateral renal arteries in eight cynomolgus monkeys, whic ... | 2018 | 29992160 |
| effects of a novel selective ep2 receptor agonist, omidenepag isopropyl, on aqueous humor dynamics in laser-induced ocular hypertensive monkeys. | to investigate the mechanism of the intraocular pressure (iop)-lowering effect of a novel selective prostaglandin e2 receptor 2 (ep2) receptor agonist, omidenepag isopropyl (omdi). | 2018 | 29989843 |
| a bridging immunogenicity assay for monoclonal antibody: case study with shr-1222. | shr-1222 is a humanized monoclonal antibody targeted to soluble sclerostin. to support the preclinical study of shr-1222 in cynomolgus monkeys, a method for the detection of anti-drug antibodies is required. | 2018 | 29987936 |
| effects of treatment delay on efficacy of tecovirimat following lethal aerosol monkeypox virus challenge in cynomolgus macaques. | tecovirimat (st-246) is being developed as an antiviral therapeutic for smallpox for use in the event of an accidental or intentional release. the last reported case of smallpox was 1978 but the potential for use of variola virus for biowarfare has renewed interest in smallpox antiviral therapeutics. | 2018 | 29982575 |
| a cynomolgus monkey model of carotid atherosclerosis induced by puncturing and scratching of the carotid artery combined with a high-fat diet. | cardio-cerebrovascular disease is one of the three major causes of mortality in humans and constitutes a major socioeconomic burden. carotid atherosclerosis (cas) is a very common lesion of the arterial walls, which leads to narrowing of the arteries, in some cases occluding them entirely, increasing the risk of cardiovascular events. the aim of the present study was to evaluate a cynomolgus monkey model of carotid atherosclerosis (cas) induced by puncturing and scratching combined with a high-f ... | 2018 | 29977359 |
| vaccination with the conserved caveolin-1 binding motif in human immunodeficiency virus type 1 glycoprotein gp41 delays the onset of viral infection and provides partial protection in simian/human immunodeficiency virus-challenged cynomolgus macaques. | we have previously reported that the cbd1 peptide (sleqiwnnmtwmqwdk), corresponding to the consensus caveolin-1 binding domain in human immunodeficiency virus type 1 (hiv-1) envelope glycoprotein gp41, elicits peptide-specific antibodies. here, we have investigated the cellular immune response and the protective efficacy against a simian/human immunodeficiency virus (shiv162p3) challenge. in addition to the cbd1 peptide, peptides overlapping the caveolin-binding-motif (cbm) (622iwnnmtwmqw631 or ... | 2018 | 29976675 |
| basic research on uterus transplantation in nonhuman primates in japan. | uterus transplantation (utx) is now a potential option for women with uterine factor infertility to have a child. however, utx is still in an experimental stage and basic animal studies including in nonhuman primates are needed for accumulation of data that will provide important information for establishment of utx in humans. herein, we summarized our experiences using cynomolgus macaques, with the goal of promoting further development of utx studies in nonhuman primates. our basic studies usin ... | 2018 | 29974599 |
| cynomolgus monkeys (macaca fascicularis) as an experimental infection model for human group a rotavirus. | group a rotaviruses (rva) are one of the most common causes of severe acute gastroenteritis in infants worldwide. rotaviruses spread from person to person, mainly by faecal⁻oral transmission. almost all unvaccinated children may become infected with rva in the first two years of life. the establishment of an experimental monkey model with rva is important to evaluate new therapeutic approaches. in this study, we demonstrated viral shedding and viraemia in juvenile⁻adult macaca fascicularis orall ... | 2018 | 29973483 |
| dynamics of immune responses during experimental mycobacterium kansasii infection of cynomolgus monkeys (macaca fascicularis). | to profile the dynamic changes of immune responses for m. kansasii infection, 3 cynomolgus monkeys were experimentally infected with m. kansasii by intratracheal inhalation of 1 × 106 cfu bacteria per monkey. every 2 to 4 weeks, tuberculin skin testings (tsts) were performed and blood samples were collected for immunoassay. multiple cytokines in a single sample were measured by luminex xmap technologies. igm and iga were detected by double-antibody sandwich elisa. igg against ppd and 11 m. tuber ... | 2018 | 29967568 |
| 2,4-diaminoquinazolines as dual toll-like receptor (tlr) 7/8 modulators for the treatment of hepatitis b virus. | a novel series of 2,4-diaminoquinazolines was identified as potent dual toll-like receptor (tlr) 7 and 8 agonists with reduced off-target activity. the stereochemistry of the amino alcohol was found to influence the tlr7/8 selectivity with the ( r) isomer resulting in selective tlr8 agonism. lead optimization toward a dual agonist afforded ( s)-3-((2-amino-8-fluoroquinazolin-4-yl)amino)hexanol 31 as a potent analog, being structurally different from previously described dual agonists ( mcgowan j ... | 2018 | 29965759 |
| selection and investigation of a primate model of spontaneous degenerative knee osteoarthritis, the cynomolgus monkey (macaca fascicularis). | background the aim of this study was to identify a primate model of degenerative knee osteoarthritis (koa) that may be more relevant for research studies on degenerative koa in humans. material and methods sixteen specific-pathogen-free (spf) male cynomolgus monkeys (macaca fascicularis) were divided into group a (n=8), an old group (22.0-25.3 years of age), and group b (n=8), a young group (3.0-5.2 years of age). for each primate, the behavior was observed, knee circumference was measured, knee ... | 2018 | 29961076 |
| neonatal fc receptor antagonist efgartigimod safely and sustainably reduces iggs in humans. | intravenous ig (ivig), plasma exchange, and immunoadsorption are frequently used in the management of severe autoimmune diseases mediated by pathogenic igg autoantibodies. these approaches modulating igg levels can, however, be associated with some severe adverse reactions and a substantial burden to patients. targeting the neonatal fc receptor (fcrn) presents an innovative and potentially more effective, safer, and more convenient alternative for clearing pathogenic iggs. | 2018 | 30040076 |
| development of a human papillomavirus type 6/11 vaccine candidate for the prevention of condyloma acuminatum. | condyloma acuminatum (ca) represents a significant human papillomavirus (hpv) disease burden worldwide, resulting in substantial healthcare costs and loss of life quality in both genders. to address this problem, we tried to develop a bivalent hpv6/11 virus-like particle (vlp) vaccine targeting ca. hpv6/11 vlps were generated in hansenula polymorpha, and a disassembly and reassembly (d/r) treatment was further conducted to improve the stability and monodispersity of the vlps. the hpv6/11 vlps we ... | 2018 | 30037483 |
| discovery of am-6226: a potent and orally bioavailable gpr40 full agonist that displays efficacy in nonhuman primates. | gpr40 (ffa1) is a g-protein-coupled receptor, primarily expressed in pancreatic islets and enteroendocrine l-cells, and, when activated, elicits increased insulin secretion only in the presence of elevated glucose levels. we recently reported the discovery of am-1638 (2), a full agonist of gpr40. herein, we present further structure-activity relationships progressing from am-1638 (2) to am-6226 (14) that possesses a profile acceptable for dosing cynomolgus monkeys. the gpr40 full agonist am-6226 ... | 2018 | 30034614 |
| an adapted isotope dilution 1h-13c heteronuclear single-quantum correlation (id-hsqc) for rapid and accurate quantification of endogenous and exogenous plasma glucose. | a wide variety of methods, such as enzymatic methods, lc-ms, and lc-ms/ms, are currently available for the concentration determination of plasma glucose in studies of diabetes, obesity, exercise, etc. however, these methods rarely discriminate endogenous and exogenous glucose in plasma. a novel nmr strategy for discriminative quantification of the endogenous and exogenous glucose in plasma has been developed using an adapted isotope dilution 1h-13c heteronuclear single-quantum correlation (id-hs ... | 2018 | 30054692 |
| non-clinical evaluation of jr-051 as a biosimilar to agalsidase beta for the treatment of fabry disease. | fabry disease (fd) is an x-linked lysosomal storage disease. it is caused by deficiency of the enzyme α-galactosidase a (α-gal a), which leads to excessive deposition of neutral glycosphingolipids, especially globotriaosylceramide (gl-3), in cells throughout the body. progressive accumulation of gl-3 causes life-threatening complications in several tissues and organs, including the vasculature, heart, and kidney. currently available enzyme replacement therapy for fd employs recombinant α-gal a i ... | 2018 | 30054149 |
| humanized anti-sialyl-tn antibodies for the treatment of ovarian carcinoma. | the expression of sialyl-tn (stn) in tumors is associated with metastatic disease, poor prognosis, and reduced overall survival. stn is expressed on ovarian cancer biomarkers including ca-125 (muc16) and muc1, and elevated serum levels of stn in ovarian cancer patients correlate with lower five-year survival rates. in the current study, we humanized novel anti-stn antibodies and demonstrated the retention of nanomolar (nm) target affinity while maintaining stn antigen selectivity. stn antibodies ... | 2018 | 30052649 |
| discovery of risdiplam, a selective survival of motor neuron-2 ( smn2) gene splicing modifier for the treatment of spinal muscular atrophy (sma). | sma is an inherited disease that leads to loss of motor function and ambulation and a reduced life expectancy. we have been working to develop orally administrated, systemically distributed small molecules to increase levels of functional smn protein. compound 2 was the first smn2 splicing modifier tested in clinical trials in healthy volunteers and sma patients. it was safe and well tolerated and increased smn protein levels up to 2-fold in patients. nevertheless, its development was stopped as ... | 2018 | 30044619 |
| immunogenicity of adenovirus-vector vaccine targeting hepatitis b virus: non-clinical safety assessment in non-human primates. | a new promising therapeutic approach has emerged for patients chronically infected by the hepatitis b virus (hbv) with the development of a non-replicative adenovirus vector vaccine candidate (ad-hbv). the vaccine encodes a fusion protein composed of a truncated hbv core protein, mutated polymerase protein, and two envelope domains. in this study, we assessed the immunogenicity of ad-hbv administered to cynomolgus monkeys during a non-clinical safety assessment. | 2018 | 30041659 |
| abt-165, a dual variable domain immunoglobulin (dvd-ig) targeting dll4 and vegf, demonstrates superior efficacy and favorable safety profiles in preclinical models. | antiangiogenic therapy is a clinically validated modality in cancer treatment. to date, all approved antiangiogenic drugs primarily inhibit the vegf pathway. delta-like ligand 4 (dll4) has been identified as a potential drug target in vegf-independent angiogenesis and tumor-initiating cell (tic) survival. a dual-specific biologic targeting both vegf and dll4 could be an attractive strategy to improve the effectiveness of anti-vegf therapy. abt-165 was uniquely engineered using a proprietary dual ... | 2018 | 29592882 |
| generation and characterization of a potent fully human monoclonal antibody against the interleukin-23 receptor. | interleukin (il)-12 and il-23 share a common subunit (p40) and function in t-helper (th) 1 and th17 immunity, respectively. anti-il-12/23p40 and specific anti-il-23 antibodies are currently in clinical use for psoriasis and undergoing trials for autoimmune diseases. since expression levels of the il-23 receptor are likely to be much lower than those of il-23, an anti-il-23 receptor antibody might offer greater promise in inhibiting the il-23-il-17 pathways involved in inflammatory disorders. to ... | 2018 | 29588152 |
| preclinical pharmacokinetics and biodistribution of subcutaneously administered glycopegylated recombinant factor viii (n8-gp) and development of a human pharmacokinetic prediction model. | essentials n8-gp is an extended half-life recombinant factor viii (fviii) for the treatment of hemophilia a. subcutaneous (sc) fviii dosing might reduce the treatment burden of prophylaxis. sc n8-gp has a favorable pk profile in animal models and disappears from skin injection sites. combined animal (sc) and clinical (iv) data suggest that daily sc dosing may provide prophylaxis. | 2018 | 29582559 |
| immune molecular profiling of whole blood drawn from a non-human primate cardiac xenograft model treated with anti-cd154 monoclonal antibodies. | most studies of xenografts have been carried out with complex immunosuppressive regimens to prevent immune rejection; however, such treatments may be fatal owing to unknown causes. here, we performed immune molecular profiling following anti-cd154 monoclonal antibody (mab) treatment in heterotopic abdominal cardiac xenografts from α-1,3-galactosyltransferase-knockout pigs into cynomolgus monkeys to elucidate the mechanisms mediating the undesirable fatal side effects of immunosuppressive agents. ... | 2018 | 29582477 |
| mechanism of activating the proprioceptive nt-3/trkc signalling pathway by reverse intervention for the anterior cruciate ligament-hamstring reflex arc with electroacupuncture. | the anterior cruciate ligament (acl) is an important structure maintaining stability of the knee joints. deficits in physical stability and the proprioceptive capabilities of the knee joints are observed, when the acl is damaged. additionally, a unilateral acl injury can affect bilateral knee proprioception; therefore, proprioception of the acl may play a key role in stability. electroacupuncture therapy has a definite effect nerve regeneration. in this study, cynomolgus monkeys were randomly di ... | 2018 | 29581981 |
| the anatomy of the foveola reinvestigated. | in the foveola of the eye, photoreceptors and müller cells with a unique morphology have been described, but little is known about their 3d structure and orientation. considering that there is an angle-dependent change in the foveolar photoreceptor response for the same light beam, known as the stiles crawford effect of the first kind (sce i), which is still not fully understood, a detailed analysis of the anatomy of the foveolar cells might help to clarify this phenomenon. | 2018 | 29576957 |
| nonclinical assessments of the potential biosimilar pf-06439535 and bevacizumab. | bevacizumab, a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor (vegf), is approved for treatment of metastatic colorectal cancer, nonsquamous non-small-cell lung cancer, metastatic kidney cancer, and glioblastoma. to support clinical development of the potential bevacizumab biosimilar pf-06439535, nonclinical studies evaluated structural, functional, toxicological, and toxicokinetic similarity to bevacizumab sourced from the european union (bevacizumab-eu) ... | 2018 | 29574193 |
| molecular characterization and polymorphisms of butyrylcholinesterase in cynomolgus macaques. | butyrylcholinesterase (bche), an enzyme essential for drug metabolism, has been investigated as antidotes against organophosphorus nerve agents, and the efficacy and safety have been studied in cynomolgus macaques. bche polymorphisms partly account for variable bche activities among individuals in humans, but have not been investigated in cynomolgus macaques. | 2018 | 29573432 |
| morphological integration of anatomical, developmental, and functional postcranial modules in the crab-eating macaque (macaca fascicularis). | integration and modularity reflect the coordinated action of past evolutionary processes and, in turn, constrain or facilitate phenotypic evolvability. here, we analyze magnitudes of integration in the macaque postcranium to test whether 20 a priori defined modules are (1) more tightly integrated than random sets of postcranial traits, and (2) are differentiated based on mode of definition, with developmental modules expected to be more integrated than functional or anatomical modules. | 2018 | 29566426 |
| preclinical pharmacokinetics, interspecies scaling, and pharmacokinetics of a phase i clinical trial of ttac-0001, a fully human monoclonal antibody against vascular endothelial growth factor 2. | vegf is a highly selective mitogen that serves as the central regulator of tumor angiogenesis by mediating endothelial proliferation, permeability, and survival. tanibirumab (ttac-0001) is a fully human igg1 monoclonal antibody derived from a fully human naïve single-chain variable fragment (scfv) phage library that was developed to inhibit the effects of vegf in the treatment of solid tumors, especially those of the brain. | 2018 | 29563774 |
| monoclonal antibody exposure in rat and cynomolgus monkey cerebrospinal fluid following systemic administration. | many studies have focused on the challenges of small molecule uptake across the blood-brain barrier, whereas few in-depth studies have assessed the challenges with the uptake of antibodies into the central nervous system (cns). in drug development, cerebrospinal fluid (csf) sampling is routinely used as a surrogate for assessing cns drug exposure and biomarker levels. in this report, we have studied the kinetic correlation between csf and serum drug concentration-time profiles for five humanized ... | 2018 | 29558954 |
| histopathologic characterization of mifepristone-induced ovarian toxicity in cynomolgus monkeys. | mifepristone, which is an orally active synthetic steroid with antiprogesterone activity, is known as an ovarian toxicant. because the available data regarding the histopathologic characteristics of ovarian toxicity in nonhuman primates are limited, the present study was undertaken in order to investigate detailed histopathologic changes accompanying mifepristone-induced ovarian toxicity and its relationship to changes in menstrual cycle and circulating sex steroid hormone. twenty mg/kg of mifep ... | 2018 | 29558845 |
| porches as enrichment for singly housed cynomolgus macaques (macaca fascicularis). | effective environmental enrichment is used by animals, promotes species-typical behavior, and decreases abnormal behavior. porches attached to the front of an animal's cage provide additional space, perching opportunities, and a better view of the surroundings. here we assessed the effectiveness of porches as a form of enrichment and identified characteristics of the animals most likely to use the porches. we videorecorded and scored the behavior of 18 (9 male, 9 female) singly housed cynomolgus ... | 2018 | 29555002 |
| absolute quantification of plasma microrna levels in cynomolgus monkeys, using quantitative real-time reverse transcription pcr. | rt-qpcr is one of the most common methods to assess individual target mirnas. mirnas levels are generally measured relative to a reference sample. this approach is appropriate for examining physiological changes in target gene expression levels. however, absolute quantification using better statistical analysis is preferable for a comprehensive assessment of gene expression levels. absolute quantification is still not in common use. this report describes a protocol for measuring the absolute lev ... | 2018 | 29553521 |
| rd-05, a novel anti-cd154 antibody, efficiently inhibits generation of anti-drug antibody without the risk of thrombus formation in non-human primates. | antibody formation against therapeutic agents, such as tumor necrosis factor inhibitors and factor viii, that leads to treatment failure has become a major challenge in the treatment of rheumatoid arthritis and hemophilia. it is well known that anti-cd154 antibodies have the highest potential to inhibit these types of adverse immune responses. nevertheless, the formation of thromboemboli is the major hurdle in the clinical application of these anti-cd154 blocking antibodies. for this, we attempt ... | 2018 | 29550477 |
| practical strategies when using a stable isotope labeled microtracer for absolute bioavailability assessment: a case study of a high oral dose clinical candidate gdc-0810. | the ph labile metabolite, hydrophobicity, high oral dose and systematic exposure of gdc-0810 posed tremendous challenges to develop a lc-ms method for a stable isotope labeled aba study. in this study, we explored practical solutions to balance stability and sensitivity and to cope with the impact of high cp.o. to ci.v. ratio on the labeling selection and assay dynamic range. a [13c9] gdc-0810 was synthesized to minimize the isotopic interference between po dose, internal standard and i.v. micro ... | 2018 | 29549853 |
| glyco-engineered long acting fgf21 variant with optimal pharmaceutical and pharmacokinetic properties to enable weekly to twice monthly subcutaneous dosing. | pharmacological administration of fgf21 analogues has shown robust body weight reduction and lipid profile improvement in both dysmetabolic animal models and metabolic disease patients. here we report the design, optimization, and characterization of a long acting glyco-variant of fgf21. using a combination of n-glycan engineering for enhanced protease resistance and improved solubility, fc fusion for further half-life extension, and a single point mutation for improving manufacturability in chi ... | 2018 | 29523796 |
| development of a non-human primate bcg infection model for the evaluation of candidate tuberculosis vaccines. | the lack of validated immunological correlates of protection makes tuberculosis vaccine development difficult and expensive. using intradermal bacille calmette-guréin (bcg) as a surrogate for aerosol mycobacterium tuberculosis (m.tb) in a controlled human infection model could facilitate vaccine development, but such a model requires preclinical validation. non-human primates (nhps) may provide the best model in which to do this. cynomolgus and rhesus macaques were infected with bcg by intraderm ... | 2018 | 29523335 |
| pharmacokinetics and toxicology of the neuroprotective e,e,e-methanofullerene(60)-63-tris malonic acid [c3] in mice and primates. | fullerene-based compounds are a novel class of molecules being developed for a variety of biomedical applications, with nearly 1000 publications in this area in the last 4 years alone. one such compound, the e,e,e-methanofullerene(60)-63-tris malonic acid (designated c3), is a potent catalytic superoxide dismutase mimetic which has shown neuroprotective efficacy in a number of animal models of neurologic disease, including parkinsonian macaca fascicularis monkeys. the aim of this study was to ch ... | 2018 | 29520718 |
| alleviating cyp and herg liabilities by structure optimization of dihydrofuran-fused tricyclic benzo[d]imidazole series - potent, selective and orally efficacious microsomal prostaglandin e synthase-1 (mpges-1) inhibitors: part-2. | in an effort to identify cyp and herg clean mpges-1 inhibitors from the dihydrofuran-fused tricyclic benzo[d]imidazole series lead 7, an extensive structure-activity relationship (sar) studies were performed. optimization of a, d and e-rings in 7 afforded many potent compounds with human whole blood potency in the range of 160-950 nm. selected inhibitors 21d, 21j, 21m, 21n, 21p and 22b provided selectivity against cox-enzymes and mpges-1 isoforms (mpges-2 and cpges) along with sufficient selecti ... | 2018 | 29519738 |
| a safety and immunogenicity study of immunization with hvegf26-104/rfase in cynomolgus monkeys. | vascular endothelial growth factor (vegf) is pivotal in tumor angiogenesis and therapies targeting the vegf axis are widely used in the clinic for the treatment of cancer. we have developed a therapeutic vaccine targeting human (h)vegf165. hvegf26-104/rfase is based on the truncated protein hvegf26-104 as antigen formulated in an oil-in-water emulsion containing the sulpholipopolysaccharide rfase as adjuvant. here we describe the toxicity and immunogenicity of this therapeutic vaccine in cynomol ... | 2018 | 29519591 |
| a sensitive method for the quantitation of the peptide-based glucagon-like peptide-1 receptor agonist liraglutide in plasma using microfluidics chromatography tandem ms. | an lc-ms/ms assay for the quantitation of liraglutide, a peptide-based injectable glucagon-like peptide-1 receptor agonist, has been developed as a convenient alternative to the enzyme-linked immunosorbent assay, and used to characterize liraglutide pharmacokinetics in cynomolgus monkeys. | 2018 | 29516741 |
| tool-use training temporarily enhances cognitive performance in long-tailed macaques (macaca fascicularis). | tool use relies on numerous cognitive functions, including sustained attention and understanding of causality. in this study, we investigated the effects of tool-use training on cognitive performance in primates. specifically, we applied the primate cognition test battery to three long-tailed macaques (macaca fascicularis) at different stages of a training procedure that consisted of using a rake to retrieve out-of-reach food items. in addition, we evaluated a control group (n = 3) performing a ... | 2018 | 29502167 |
| visual stimulation-induced mild stress enhances cognitive behavior in cynomolgus monkey. | cortisol is a well-known endogenous glucocorticoid that serves as a stress indicator. it is normally released under stressful condition to warn about imminent danger and thus is critical for survival of the species. however, it is unclear how cortisol relates to cognitive process under physiological condition in high-order primates such as non-human primates (nhp). here, we report that a slight but significant increase in blood cortisol level by mild stress is positively correlated with the cogn ... | 2018 | 29491446 |
| reduced red blood cell deformability in plasmodium knowlesi malaria. | the simian parasite plasmodium knowlesi can cause severe and fatal human malaria. however, little is known about the pathogenesis of this disease. in falciparum malaria, reduced red blood cell deformability (rbc-d) contributes to microvascular obstruction and impaired organ perfusion. in p knowlesi infection, impaired microcirculatory flow has been observed in macaca mulatta (rhesus macaques), unnatural hosts who develop severe and fatal disease. however, rbc-d has not been measured in human inf ... | 2018 | 29487058 |
| spontaneous hypertrophic cardiomyopathy in a cynomolgus macaque (macaca fascicularis). | the term cardiomyopathy is used to describe heart disease resulting from an abnormality in the myocardium. it is rare in cynomolgus macaques (macaca fascicularis). here, we report a case of hypertrophic cardiomyopathy in an 11-year-old male cynomolgus macaque. macroscopically, the interventricular septum (ivs) and the left ventricular (lv) and right ventricular (rv) walls of the heart were thickened. histologically, cardiomyocytes showed hypertrophy and disarray with interstitial fibrosis, and s ... | 2018 | 29479140 |
| circulating liver-specific micrornas in cynomolgus monkeys. | circulating micrornas (mirnas) can potentially be used as sensitive and specific biomarkers for tissue injury. however, the usefulness of circulating mirnas as safety biomarkers in nonclinical toxicological studies using nonhuman primates is debatable owing to the limited information on organ-specific mirnas. therefore, a systematic investigation was performed to address this point. we identified organ-specific mirnas from cynomolgus monkeys by next-generation sequencing analysis, which revealed ... | 2018 | 29479135 |
| spontaneous findings in the eyes of cynomolgus monkeys ( macaca fascicularis) of mauritian origin. | spontaneous findings noted in the eyes of mauritian cynomolgus monkeys are described and descriptions are supplemented with illustrations. findings observed after extensive histopathologic examinations (20 to 44 sections per eye) from 20 control, 17 treatment-naive stock monkeys, and 2 findings noted in drug-treated monkeys that were considered to be spontaneous are included. also included are findings from 361 control monkeys of routine toxicity studies performed at our laboratories, for most o ... | 2018 | 29478386 |
| human igg subclass cross-species reactivity to mouse and cynomolgus monkey fcγ receptors. | in therapeutic antibody discovery and early development, mice and cynomolgus monkey are used as animal models to assess toxicity, efficacy and other properties of candidate molecules. as more candidate antibodies are based on human immunoglobulin (igg) subclasses, many strategies are pursued to simulate the human system in the test animal. however, translation rate from a successful preclinical trial to an approved drug is extremely low. this may partly be due to differences in interaction of hu ... | 2018 | 29476755 |
| the development of new factor xa inhibitors based on amide synthesis. | factor xa (fxa) is known to play a central role in blood coagulation cascade and considered to be one of the most attractive targets for oral anticoagulants of new generation. | 2018 | 29468977 |
| polymorphisms of cytochrome p450 2b6 (cyp2b6) in cynomolgus and rhesus macaques. | cytochrome p450 2b6 (cyp2b6) is an important drug-metabolizing enzyme and is expressed in liver. although human cyp2b6 variants account for variable enzyme properties among individuals and populations, cyp2b6 genetic variants have not been investigated in cynomolgus macaques, widely used in drug metabolism studies. | 2018 | 29468688 |
| pilot study of delayed icos/icos-l blockade with αcd40 to modulate pathogenic alloimmunity in a primate cardiac allograft model. | inducible costimulator (icos) is rapidly upregulated with t-cell stimulation and may represent an escape pathway for t-cell costimulation in the setting of cd40/cd154 costimulation blockade. induction treatment exhibited no efficacy in a primate renal allograft model, but rodent transplant models suggest that the addition of delayed icos/icos-l blockade may prolong allograft survival and prevent chronic rejection. here, we ask whether icos-ig treatment, timed to anticipate icos upregulation, pro ... | 2018 | 29464205 |
| generation and characterization of a novel small biologic alternative to proprotein convertase subtilisin/kexin type 9 (pcsk9) antibodies, ds-9001a, albumin binding domain-fused anticalin protein. | since it was recently reported that an antibody for proprotein convertase subtilisin/kexin type 9 (pcsk9) reduces the risk of cardiovascular events in a clinical context, pcsk9 inhibition is thought to be an attractive therapy for dyslipidemia. in the present study, we created a novel small biologic alternative to pcsk9 antibodies called ds-9001a, comprising an albumin binding domain fused to an artificial lipocalin mutein (abd-fused anticalin protein), which can be produced by a microbial produ ... | 2018 | 29463608 |
| integrated pharmacokinetic/pharmacodynamic model of a bispecific cd3xcd123 dart molecule in nonhuman primates: evaluation of activity and impact of immunogenicity. | purpose: flotetuzumab (mgd006 or s80880) is a bispecific molecule that recognizes cd3 and cd123 membrane proteins, redirecting t cells to kill cd123-expressing cells for the treatment of acute myeloid leukemia. in this study, we developed a mathematical model to characterize mgd006 exposure-response relationships and to assess the impact of its immunogenicity in cynomolgus monkeys.experimental design: thirty-two animals received multiple escalating doses (100-300-600-1,000 ng/kg/day) via intrave ... | 2018 | 29463552 |
| peripheral defocus of the monkey crystalline lens with accommodation in a lens stretcher. | to characterize the peripheral defocus of the monkey crystalline lens and its changes with accommodation. | 2018 | 29801154 |
| a macaca fascicularis knee osteoarthritis model developed by modified hulth combined with joint scratches. | background osteoarthritis is a common degenerative disease of joints, and animal models have important significance in the investigation of this disease. the aim of this study was to develop a better method for developing osteoarthritis models in primates by comparing the modified hulth score combined with joint scratches modeling method with others. material and methods we randomly divided 15 young male macaca fascicularis and 3 old male macaca fascicularis into 6 groups (n=3). knee osteoarthri ... | 2018 | 29789519 |
| methylprednisolone inhibits the proliferation of endogenous neural stem cells in nonhuman primates with spinal cord injury. | objective the aim of this work was to investigate the effects of methylprednisolone on the proliferation of endogenous neural stem cells (enscs) in nonhuman primates with spinal cord injury (sci). methods a total of 14 healthy cynomolgus monkeys ( macaca fascicularis) (4-5 years of age) were randomly divided into 3 groups: the control group (n = 6), sci group (n = 6), and methylprednisolone therapy group (n = 2). only laminectomy was performed in the control animals at t-10. sci was induced in m ... | 2018 | 29775163 |
| discovery of a novel il-15 based protein with improved developability and efficacy for cancer immunotherapy. | interleukin-15 (il-15) can promote both innate and adaptive immune reactions by stimulating cd8+/cd4+ t cells and natural killer cells (nk) while showing no effect in activating t-regulatory (treg) cells or inducing activation-associated death among effector t cells and nk cells. thus, il-15 is considered as one of the most promising molecules for antitumor immune therapy. to improve the drug-like properties of natural il-15, we create an il-15-based molecule, named p22339, with the following ch ... | 2018 | 29769573 |
| effects of monoclonal antibodies against nerve growth factor on healthy bone and joint tissues in mice, rats, and monkeys: histopathologic, biomarker, and microcomputed tomographic assessments. | tanezumab, an anti-nerve growth factor (ngf) antibody, is in development for management of chronic pain. during clinical trials of anti-ngf antibodies, some patients reported unexpected adverse events requiring total joint replacements, resulting in a partial clinical hold on all ngf inhibitors. three nonclinical toxicology studies were conducted to evaluate the effects of tanezumab or the murine precursor mumab911 on selected bone and joint endpoints and biomarkers in cynomolgus monkeys, spragu ... | 2018 | 29768985 |
| pain-related behavior and brain activation in a cynomolgus macaque model of postoperative pain. | inadequate postoperative pain management could lead to persistent pain and this is, in part, due to incomplete understanding of the mechanism of postoperative pain. currently available rodent models may have limited translatability to clinical postoperative pain. thus, a preclinical model of postoperative pain was developed in the cynomolgus macaque, a species that is phylogenetically closer to humans than rodents. | 2018 | 29766827 |
| are monkeys intuitive aristotelians? associations between target size and vertical target position in long-tailed macaques. | different hypotheses have been put forward to explain the interaction between size perception and spatial position. to explore the evolutionary roots of these phenomena, we tested long-tailed macaques' performance in a two-choice discrimination task on a touchscreen and contrasted two hypotheses. first, a hierarchy association in which large objects are associated with top positions, due to a link between power, dominance and importance with top position. second, a naive aristotelian association ... | 2018 | 29765622 |
| cochlear implant electrode array from partial to full insertion in non-human primate model. | to determine the feasibility of progressive insertion (two sequential surgeries: partial to full insertion) of an electrode array and to compare functional outcomes. | 2018 | 29764773 |
| prediction of non-linear pharmacokinetics in humans of an antibody-drug conjugate (adc) when evaluation of higher doses in animals is limited by tolerability: case study with an anti-cd33 adc. | for antibody-drug conjugates (adcs) that carry a cytotoxic drug, doses that can be administered in preclinical studies are typically limited by tolerability, leading to a narrow dose range that can be tested. for molecules with non-linear pharmacokinetics (pk), this limited dose range may be insufficient to fully characterize the pk of the adc and limits translation to humans. mathematical pk models are frequently used for molecule selection during preclinical drug development and for translatio ... | 2018 | 29757698 |
| metabolism of an oxime-linked antibody drug conjugate, ags62p1, and characterization of its identified metabolite. | ags62p1 is an antibody drug conjugate (adc) composed of a human igg1κ monoclonal antibody against flt3 (fms-like tyrosine kinase 3) with a p-acetyl phenylalanine (paf) residue inserted at position 124 of each heavy chain linked to the proprietary microtubule disrupting agent agl-0182-30 via an alkoxyamine linker that forms an oxime upon conjugation to the antibody. ags62p1 is currently in phase i human clinical trials for acute myelogenous leukemia (aml). the identified primary metabolite of an ... | 2018 | 29757653 |