Diabetic retinopathy (DR) is a common complication of diabetes due to abnormalities in retinal blood vessels. Initially, the retinal vessel changes are non-proliferative, thus termed as non-proliferative DR (NPDR). As NPDR progresses, the micro-vessels leak to form macular edema or even close off to cause macular ischemia. Both forms of lesions can lead to the partial loss of vision or blurry.
Chronic kidney disease (CKD) including diabetic nephropathy (DN) occurs in approximately 20-40% of the type 2 diabetes (T2D) global population. At KBI, our cynomolgus monkey models of CKD and DN closely resemble all the characteristics of these diseases in humans and they have been successfully used to evaluate the new drugs for this disease.
KBI has a cohort of monkeys with spontaneous hypertension identified by the measurement of blood pressure (BP) with High Definition Oscillometry (HDO). Through the screening of a large cohort of monkeys, KBI has established the normal range of BP and diagnostic values for hypertension in monkeys:
KBI has a large colony of obese NHP models readily available for the needs of research services.
We routinely evaluate anti-obese efficacy with a wide range of tools including the following techniques:
· measurements of caloric intake and body mass index (BMI)
· quantification of body fat composition with dual energy X-ray absorptiometry (DEXA and iDXA)
· measurement of ectopic fat accumulation with magnetic resonance imaging (MRI)
· molecular biomarkers (such as adipokine mRNA expression) from fat biopsy in the area of interest
KBI has large colonies of cynomolgus macaque models of spontaneous and diet-induced obese with a wide range of metabolic disorders including metabolic syndrome, diabetes and other related comorbidities. The diet-responsive colonies of obese cynomolgus macaques induced by KBI proprietary Western-type of high fat diet (HFD). In these monkeys, our HFD predominantly incudes central obesity and the metabolic syndrome effects with a greater propensity to diabetes, non-alcoholic fatty liver disease, cardiovascular disease and chronic kidney disease. The following models of obesity and metabolic syndrome in cynomolgus monkeys are available at KBI:
· Spontaneous and diet-induced obesity with typical phenotype of the metabolic syndrome
· Spontaneous and diet-induced insulin resistance
· Spontaneous and diet-induced impaired glucose tolerance (pre-diabetic model)
· Spontaneous and diet-induced atherogenic dyslipidemia
· Spontaneous and diet-induced hypertension
KBI has a range of tools for the characterization of whole body and fat composition including dual energy X-ray absorptiometry (DEXA), anthropometry, BMI, abdominal circumference, skin-fold thickness and in-house laboratory assays for circulating lipids and biomarkers for obesity-associated disease.
KBI establishes Parkinson Disease (PD) Models through:
1. Systemic MPTP (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine) Administration
Osteoarthritis (OA) is a global degenerative joint disease that affects over 10% of the world’s population aged 60 years or older. Despite the recent availability of more advanced imaging modalities, controlled investigations of structural and biochemical changes in human osteoarthritic joints are still restricted by the relative inaccessibility of diseased tissues for sampling and the ethical limitations in the use of sham interventions or placebo, and in obtaining control human tissues. Thus, animal OA models are used to study the disease pathogenesis and to evaluate the potential effects of various therapeutic agents intended for human/clinical use.
Age-related macular degeneration (AMD) is a common eye disease that leads to the central vision loss among people age over 50 years. There are two types of AMD: dry (atrophic) and wet (neovascular or exudative). Ten to 20% of AMD patients will progress to wet AMD.
KBI has the capability of producing different models of stroke, such as middle cerebral artery (MCAo) model and thromboembolism, in monkeys to mimic the pathophysiology of different types of strokes in patients. One of the commonly used stroke models is the ligation of unilateral MCAo followed by the removal of the occlusion through craniotomy surgery. This stroke model mimics the pathophysiology of ischemic-reperfusion in patients and the impact of craniotomy is manageable by comparing with the contralateral side by a range of assessments (Fig 1). This model is readily available for the evaluation of neuroprotective pharmaceutical agents.
Myocardial infarction and heart failure are leading causes of the mortality worldwide. The NHP models of myocardial ischemia/reperfusion injury are very unique for the evaluation of new therapeutics (particularly protein products and gene therapies) to clinical application devoid of inter-species variations.
KBI has two monkey models of inflammatory bowel disease (IBD) available for the evolution of therapeutic agents and the investigation of the pathogenic mechanisms. One model is spontaneously developed where KBI utilizes colonoscopy to identify ulcerative colitis with characteristic clinical signs of chronic or recurrent IBD.