March 4th, marks World Obesity Day. The World Health Organization (WHO) data reveals a continuing global surge in obesity rates, now recognized as a significant public health crisis. Obesity extends beyond cosmetic concerns, being intrinsically linked to a spectrum of chronic diseases including cardiovascular disease, diabetes, and metabolic-associated steatohepatitis (MASH). Facing this escalating challenge, the development of next-generation anti-obesity therapies is of paramount urgency.
Encouragingly, recent years have witnessed transformative progress in obesity treatment, spearheaded by innovative drug classes such as glucagon-like peptide-1 (GLP-1) receptor agonists. From Novo Nordisk's Wegovy to Eli Lilly's Zepbound, and further expanding to investigational therapies targeting multiple signaling pathways, enhancing administration convenience, and employing novel mechanisms of action, the field of anti-obesity drug development is experiencing unprecedented momentum.
Within this dynamic landscape of anti-obesity drug discovery, preclinical research plays a critical role. High-quality animal models, particularly non-human primate (NHP) models that closely mirror human physiology, are essential for generating robust efficacy and safety data, thereby accelerating the drug development pipeline.
Prisys Biotech, an AAALAC-accredited contract research organization (CRO) specializing in preclinical and non-clinical drug evaluation and new drug technology development, has cultivated extensive expertise in metabolic disease research. We have established a comprehensive NHP metabolic model platform. On this World Obesity Day, Prisys Biotech is pleased to introduce our advanced NHP metabolic models, designed to empower your anti-obesity drug development endeavors.
Staying Ahead: New Trends in Anti-Obesity Therapy Development
As highlighted in recent industry analyses, several emerging trends are shaping the direction of anti-obesity therapy research:
Targeting Multiple Signaling Pathways: The focus is shifting from single-target GLP-1 agonists to multi-target approaches. This includes dual agonists like GIP/GLP-1 receptor agonists, triple agonists targeting GIP, GLP-1, and glucagon receptors, and even antibody-drug conjugates that combine GLP-1 analogs with GIP receptor antagonists. This multi-pronged strategy aims to comprehensively modulate appetite and metabolism, maximizing weight loss efficacy.
Enhanced Administration Convenience: Efforts are underway to improve patient adherence and accessibility through more convenient dosing regimens. This includes long-acting formulations for less frequent injections (e.g., monthly) and the development of oral small molecule drugs for daily administration.
Novel Targets and Mechanisms: Genetic studies are uncovering new targets beyond incretin pathways, opening avenues for innovative therapeutic strategies. Examples include therapies targeting genes like INHBE using RNA interference (RNAi) and peripherally selective cannabinoid receptor 1 (CB1) inhibitors designed to minimize central nervous system side effects.
Muscle Sparing and Long-Term Health: Beyond weight reduction, maintaining muscle mass and improving long-term health outcomes are increasingly recognized as crucial goals for next-generation anti-obesity therapies. Approaches targeting activin receptor type II (ActRII), myostatin inhibitors, and selective androgen receptor modulators (SARMs) are being investigated for their potential to promote fat loss while preserving or even increasing muscle mass.
Prisys Biotech NHP Metabolic Models: Precise Mimicry, Accelerating Your Research
Prisys Biotech understands the critical needs of anti-obesity drug development. We have meticulously developed a range of NHP models for obesity and related metabolic disorders, supported by extensive model characterization and pharmacodynamic evaluation data. Our NHP metabolic model platform provides robust support for your anti-obesity drug research:
1. Obesity Model (Macaca fascicularis Obesity Model)
Model Establishment: Induced by long-term high-energy diet feeding.
Model Characteristics:
Increased body weight and body fat percentage.
Potential development of insulin resistance, hyperglycemia, hyperlipidemia, and other metabolic disturbances.
Obesity severity assessable through body weight, body fat percentage, BMI, waist circumference, etc.
Dysregulation of metabolic parameters such as blood glucose, insulin, and lipids.
Pharmacodynamic Applications:
Evaluation of anti-obesity drug efficacy, such as appetite suppressants, fat absorption inhibitors, energy expenditure enhancers.
Evaluation of drug efficacy in treating obesity-related metabolic disorders, such as GLP-1 receptor agonists and SGLT2 inhibitors.
Monitored endpoints: Changes in body weight, body fat percentage, improvements in metabolic parameters, incidence of obesity-related complications.
Prisys Biotech's Macaca fascicularis obesity model accurately recapitulates the physiological characteristics of human obesity, making it an ideal choice for evaluating novel anti-obesity drugs targeting multiple signaling pathways and muscle-sparing strategies.
2. Type 1 Diabetes Mellitus (T1DM) Model (Macaca fascicularis T1DM Model)
Model Establishment: Induced by pancreatic β-cell destruction, to absolute insulin deficiency.
Model Characteristics:
Severe insulin deficiency or absence, hyperglycemia, glucosuria.
Weight loss, polydipsia, polyuria, polyphagia (classic "polyuria, polydipsia, and polyphagia" symptoms).
Long-term hyperglycemia can lead to diabetic complications.
Abnormalities in blood glucose, insulin levels, oral glucose tolerance test (OGTT), and insulin tolerance test (ITT).
Pharmacodynamic Applications:
Evaluation of therapies for T1DM, such as insulin preparations, islet cell transplantation, stem cell therapy, and immunomodulatory therapies.
Monitored endpoints: Blood glucose, HbA1c, glucose tolerance, insulin levels, incidence of diabetic complications.
Prisys Biotech's T1DM model can be utilized to investigate the pathogenesis and treatment strategies for obesity-related T1DM, and to evaluate the efficacy of novel insulin formulations and cell-based therapies.
3. Type 2 Diabetes Mellitus (T2DM) Model (Macaca fascicularis T2DM Model)
Model Establishment: High-fat diet feeding (long-term high-fat, high-sugar diet feeding more readily induces T2DM).
Model Characteristics:
Insulin resistance; compensatory hyperinsulinemia in early stages, followed by pancreatic β-cell dysfunction and insulin deficiency in later stages.
Hyperglycemia (generally less severe than in T1DM), obesity, dyslipidemia.
Abnormal glucose tolerance test, elevated Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).
Long-term hyperglycemia can lead to diabetic complications.
Pharmacodynamic Applications:
Evaluation of therapies for T2DM, such as insulin sensitizers (e.g., metformin, pioglitazone), insulin secretagogues (e.g., sulfonylureas, glinides), GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors.
Monitored endpoints: Blood glucose, HbA1c, glucose tolerance, insulin levels, HOMA-IR, lipids, body weight, incidence of diabetic complications.
Prisys Biotech's T2DM model accurately mimics the complex pathophysiology of human T2DM, serving as an ideal model for evaluating anti-diabetic drugs targeting various mechanisms, as well as multi-target combination therapies.
4. Insulin Resistance Model (Macaca fascicularis Insulin Resistance Model)
Model Establishment: High-fat diet feeding, chronic administration of glucocorticoids.
Model Characteristics:
Reduced insulin sensitivity in peripheral tissues (e.g., muscle, adipose tissue), impaired insulin-mediated glucose uptake and utilization.
Blood glucose may be normal or mildly elevated, compensatory hyperinsulinemia.
Abnormal insulin tolerance test (ITT) results.
Abnormal glucose clamp test results (gold standard for assessing insulin resistance).
Pharmacodynamic Applications:
Evaluation of therapies for improving insulin resistance, such as insulin sensitizers and novel insulin-sensitizing agents.
Monitored endpoints: Insulin tolerance test results, glucose clamp test parameters, HOMA-IR, blood glucose, insulin levels, lipids.
Prisys Biotech's insulin resistance model is valuable for in-depth studies of insulin resistance mechanisms and for evaluating the efficacy of novel insulin sensitizers, addressing a core issue in metabolic diseases.
5 & 6. Hyperlipidemia & Hypercholesterolemia Models (Macaca fascicularis Models)
Model Establishment: High-fat, high-cholesterol, high-fructose diet (Hyperlipidemia); High-cholesterol diet (Hypercholesterolemia).
Model Characteristics:
Elevated lipid levels (TC, TG, LDL-C, HDL-C) (Hyperlipidemia); Significantly elevated serum TC and LDL-C (Hypercholesterolemia).
Long-term hyperlipidemia/hypercholesterolemia may lead to atherosclerotic cardiovascular disease.
Xanthomas may develop in hypercholesterolemia model.
Pharmacodynamic Applications:
Evaluation of lipid-lowering/cholesterol-lowering drug efficacy, such as statins, fibrates, PCSK9 inhibitors, ANGPTL3 inhibitors.
Monitored endpoints: Lipid levels (TC, TG, LDL-C, HDL-C), extent of atherosclerotic lesions (assessed by vascular ultrasound, angiography, or histopathology), xanthoma size (Hypercholesterolemia model).
Prisys Biotech's hyperlipidemia and hypercholesterolemia models are suitable for evaluating novel lipid-lowering drugs, particularly those targeting emerging targets like PCSK9 and ANGPTL3, as well as early intervention strategies for atherosclerosis.
7. Acute Hypertension Model (Macaca fascicularis Acute Hypertension Model)
Model Establishment: Rapid induction of vasoconstriction or increased cardiac output.
Model Characteristics:
Rapid elevation of blood pressure (both systolic and diastolic).
Heart rate may increase.
Pharmacodynamic Applications:
Evaluation of the rapid blood pressure-lowering effects of antihypertensive drugs, such as vasodilators and diuretics.
Monitored endpoints: Blood pressure reduction magnitude, rate of blood pressure lowering, duration of effect.
Prisys Biotech's acute hypertension model can be used to evaluate rapid-acting antihypertensive drugs for emergency situations, providing preclinical data to support the treatment of hypertensive crises.
Prisys Biotech: Your Trusted NHP Model Partner
Prisys Biotech boasts a highly experienced team in animal model development and pharmacodynamic evaluation, along with internationally recognized AAALAC-accredited facilities. We are committed to providing global drug discovery companies with high-quality NHP models and expert services, accelerating innovation in metabolic disease treatment and collaboratively addressing the global obesity challenge.
If you are engaged in drug development for metabolic diseases, particularly obesity and related complications, Prisys Biotech's NHP model platform is your ideal partner.
Contact us today to learn more about Prisys Biotech NHP Metabolic Models and embark on your accelerated drug discovery journey!
