Therapeutic Areas

Therapeutic drugs, biologics and devices require regulatory animal safety and efficacy studies prior to first use in human. Sinclair Research conducts many types of animal model studies to investigate the mechanism and pathobiology of disease. We offer models which cover many therapeutic areas, including metabolic disease, diabetes, infection, pain and inflammation, arthritis, cardiovascular disease, geriatric issues, and neurological deficits.

Metabolic Disease

Metabolic disease and diabetes are ever-growing medical problems in today’s society. Pathophysiological and metabolic changes associated with the onset and development of diabetes mellitus can be modeled in laboratory animals by chemical induction, genetic intervention, or dietary modification. Chemically-induced Type I diabetic miniature swine models have been in use at Sinclair Research for over 10 years. Our staff is very experienced in the area of miniature swine diabetes induction and evaluation of candidate therapeutics. We continually maintain a large herd of diabetic Yucatan miniature swine as a resource for studies. Sinclair has expanded its diabetes and metabolic disease programs, developing other clinically-relevant models in multiple species such as rodents, canines, and NHPs. Glucose tolerance, insulin resistance testing, and insulin potency testing are routinely included in studies.

 

Animal Models

Spontaneous/Genetic Models:

  • Obesity
  • Metabolic syndrome
  • Hypertension
  • Type II diabetes

Induced Models:

  • Specialized diets
  • Chemicals
  • Surgical
  • Type I & II diabetes

Available Clinical Assessments

  • DEXA analysis
  • Urine chemistry
  • Food and water consumption
  • Serum chemistry
  • Lipid profiles
  • Liver function tests
  • Kidney function profile
  • Hormones and biomarkers
  • Glucose disposal (oGTT and ivGTT)
  • Hyperinsulinemic-glycemic clamp

Diabetes

The diabetic miniature swine is a widely-recognized translational model for the evaluation of drugs, nutritional therapies, medical devices, and various therapeutic approaches to treatment of diabetes and its metabolic disease complications. Sinclair Research has produced and worked intensively with Type I diabetes mellitus miniature swine since 2001. We are experts in diabetes induction, diabetes maintenance, and conduction of drug or therapeutic pharmacokinetic and pharmacodynamic (PK/PD) studies in the diabetic miniature swine. We offer various types of clamps for your study, including euglycemic, hyperglycemic, hyperinsulinemic, and Bergmann’s.

We currently maintain more than 250 insulin-dependent diabetic miniature swine in-house, enabling us to offer a wide variety of research services using diabetic models; we additionally make the diabetic miniature swine available to industry and academic clients through our sister company, Sinclair Bio Resources. 

Miniature Swine Diabetic Model Flexibility

The diabetic miniature swine model is a very versatile model for studies on diabetes management. Sinclair Research has three breeds of miniature swine, Yucatan, Micro-Yucatan, and Sinclair, available for use in a variety studies targeting diabetes-related research areas and therapy types, as listed below.

 

Applicable Research Areas

  • Type I or Type II diabetes complications
  • Insulin resistance
  • Wound healing, including delayed healing
  • Cataracts and retinopathy
  • Obesity
  • Atherosclerosis
  • Dyslipidemia and hypercholesterolemia
  • Hypertension
  • Cardiometabolic syndrome

Therapy Types

  • Insulin, insulin analogues, insulin sensitizers, β-cell multipliers, cellular therapies
  • Small and large molecules, most compounds targeting glucose and lipid activity

Inflammation

Pathophysiological changes associated with inflammation and disease onset can be modeled in laboratory animals by chemical induction, pharmacological intervention, or surgical modification. Sinclair Research has expanding pharmacology and inflammatory diseases programs, including disease-relevant models of inflammatory joints and osteoarthritis in multiple species. We conduct studies with customized anti-inflammatory drug pharmacodynamic end points to meet each client’s objectives.

 

Disease Areas

  • Wound healing
  • Rheumatoid arthritis and osteoarthritis
  • Inflammation drugs
  • Joint inflammation
  • Dermal diseases
  • Inflammatory bowel diseases
  • Sepsis and endotoxemia
  • Atherosclerosis

Animal Models

  • Anterior cruciate ligament (ACL)-transection osteoarthritis in rabbits, pigs, and dogs
  • Dermal edema and hypersensitivity in mice
  • Atopic dermatitis in dogs and NHPs
  • Sepsis and endotoxemia in mice, dogs, and NHPs
  • Ulcerative colitis and Crohn’s disease in mice and rats
  • Wound healing in normal and diabetic pigs
  • Atherosclerosis in pigs and rabbits

Pharmacodynamic Assessments

  • Specific clinical disease indexes for functional evaluation of efficacy
  • Fluid and blood cells differential counts
  • Serum and urine chemistry
  • Tissue, fluid, and blood cytokines levels
  • Efficacy and safety biomarkers
  • Histopathology of soft and hard tissues
  • Specific histology-based severity of disease indexes
  • Histomorphometry for tissue damage evaluation
  • Immunohistochemistry of key tissue and inflammatory markers

Applicable Research Areas

  • Dermatology, dermal inflammation, and wound healing
  • Cartilage and joint diseases, osteoarthritis
  • Gastro-intestinal and irritable bowel diseases

Dermal

Sinclair Research is a Center of Excellence for Dermal Research with a broad range of capabilities, expertise, and best practices.  Sinclair personnel are experts in dermal toxicity testing, conducting GLP-compliant dermal and transdermal toxicology and safety studies.  In addition to toxicology, Sinclair supports a wide range of drug metabolism and pharmacokinetic (DMPK) studies and efficacy studies, including wound healing and inflammatory studies in an FDA-recommended model, the miniature swine. The Sinclair research team has experience with all conventional routes of compound administration, including transdermal (passive and active), dermal applications (ointments, creams, lotions) and dermal applications specialized devices.

We are used to working with all commonly used research lineages of miniature swine, namely, the Hanford, Gottingen, Sinclair, and Yucatan.  The Hanford miniature swine, which have white skin and available from  Sinclair Bio Resources, have been used for over 20 years as a model for dermal studies. Sinclair has developed a white, hairless Yucatan miniature swine breed for dermal absorption, irritation, and photosensitivity studies. The Sinclair miniature swine have also been selected for white skin and are smaller than either the Yucatan or Hanford lineages; they are appropriate models for dermal studies as well.

In addition to miniature swine, Sinclair offers dermal studies in a number of other species, including mice, rats, rabbits, guinea pigs, dogs, and non-human primates.

 

Services offered include:

  • Dermal Toxicity Testing
  • Acute, short-term (7- to 28-day), subchronic (90-day), or chronic exposure durations
  • Single or repeat dose, occluded or non-occluded administration site
  • Passive and active (iontophoretic) dermal/transdermal patch administration
  • Dermal evaluation of irritation, sensitization, and local tolerance
  • Phototoxicity and photoallergy models
  • Standard toxicology endpoints – clinical observations, clinical pathology, ECG, ophthalmology, histopathology
  • Dermal drug metabolism and pharmacokinetic (DMPK) studies
  • Pharmacokinetics and toxicokinetics for dermal/transdermal routes of administration
  • Cross-contamination prevention – custom equipment for dermal studies
  • A dedicated dermal study team for scoring (Draize, Magnusson and Kligman grading) and photography
  • Custom large animal enclosures for dermal studies, utilizing stainless steel full barriers
  • Dose preparation

Other Skin Models

  • Full-thickness and partial thickness dermal wounds, skin barrier interruption by scarification and tape stripping of the stratum corneum
  • Skin allergy, atopy, depigmentation

Wound Healing

Sinclair has performed dermal wound healing studies in miniature swine models for many years; other species are available for wound studies as well. Resident experts provide guidance to our wound healing program.

We offer wound healing studies with a wide variety of dermal wound sizes, shapes, depths, and designs including:

  • Incisional
  • Excisional – full thickness or partial thickness
  • Ischemic wound
  • Burn wound
  • Delayed wound healing studies in diabetic miniature swine
  • Classic wound healing endpoints in miniature swine models
  • Digital measurement of serial wound areas
  • 3D photography for wound depth and volume
  • Histopathology evaluation of re-epithelialization
  • Large definitive GLP and small pilot studies

We ensure that study designs are humane and include analgesic use.

Orthopedic Studies

The basic infrastructure required for successful execution of orthopedic projects exists at Sinclair Research, where non-regulatory and GLP studies in both large and small animal models are routine. Sinclair utilizes clinical veterinarians as well as outside surgical interventionalists to support these studies. An independent expert in orthopedic models is also available for study design and protocol development and in-life study auditing on large, complex and intensive studies.

Osteoarthritis, cartilage and bone healing and repair, and osteoporosis are among the orthopedic studies offered at Sinclair Research, as well as implantable devices tested on, in, or adjacent to a variety of bone classes.

We offer several animal species as models for use in these and other protocols:

 

  • Osteoarthritis
    • ACL transection
    • Clinical endpoints – joint fluid, gait, pain, and histology
  • Rheumatoid arthritis
  • Trauma models
    • Femur, radius, fibula, rib, or pelvis fractures
    • Tibial, femoral, or ulnar osteotomy models
  • Osteopenia and osteoporosis
    • Ovarioectomy- and orchidectomy-induced
    • Steroid-induced
    • Calcium-restricted diet induced
  • Joint cartilage defect and repair
  • ACL rupture repair models
  • Reconstruction and fixation of ligaments and tendons
  • Meniscal repair
  • Spinal vertebral fusion models
  • Intervertebral disc models
  • Critical-size long bone defect model
  • Mandibular defect
  • Bone drug safety and efficacy
  • Intra-articular joint injection and sampling
  • Bone ingrowth for joint replacement
  • Axial and transcortical non-weight bearing studies
  • Evaluations of bone cements, putties, and fillers
  • Spine and spinal cord injury
  • Ortho device safety and efficacy, osteoinduction and osteoconduction studies
  • Morphometrics and biomechanical testing

Ocular Studies

Sinclair Research is proud to have assembled an exceptional combination of experience and resources for pre-clinical in-vivo evaluation of ocular therapeutics. We conduct GLP and non-GLP ophthalmic studies ranging from simple to complex design in a variety of animal models for safety, efficacy, drug metabolism and pharmacokinetic (DMPK), and ocular biodistribution evaluations. Whether supporting the development of ophthalmic drugs, devices, or drug-eluting devices, Sinclair is well-equipped to provide clients with required essentials, ranging from technology and facilities to board-certified consultants and ocular histopathology reports, to execute specialized, high-quality studies.

 

Study Services

  • Ocular toxicology
  • Ocular pharmacology
  • Treatment efficacy
  • Drug-eluting implants
  • Ocular and periocular infection
  • Fundus evaluation
  • Vitreo-retinal surgery
  • ERG
  • Tonometry
  • Digital imaging, anterior and posterior segments
  • Ocular drug distribution

Specialized Animal Models

  • Normal intra-ocular pressure (IOP) in rabbits and NHP
  • Elevated IOP in rabbits, NHPs, and miniature swine
  • Laser-induced glaucoma
  • Miniature swine diabetic retinopathy and cataracts
  • Transgenic retinal degeneration model

Ocular Routes of Administration

  • Topical
  • Intravitreal
  • Intracameral
  • Subretinal injection, including stem cells
  • Subconjunctival
  • Drug-eluting device implantation
  • Punctal plugs