Pharmacological Efficacy Studies


We off a variety of animal models. Please contact us if you are looking for animal models other than below. We are able to develop models that meet your needs.

 

Osteoporosis Model

The animals used are either aged female cynomolgus monkeys in which epiphyseal closure has been confirmed by X-ray examination, or aged female rats with mature skeletons. After ovariectomy, bone turnover markers that reflect bone formation and bone resorption increase, bone density decreases temporally, and the structural parameters that reflect bone strength also decrease. Using bone turnover markers and bone strength parameters, we evaluate the therapeutic or preventive effects of the test article.

 

Bone Turnover Markers Measurement

After single or repeated administration of the test article to each animal species (mainly rats and monkeys), we evaluate the temporal effect on bone formation markers, bone resorption markers, and bone quality markers in urine and blood.

・Urine: Pyridinoline, Deoxypyridinoline, NTX, CTX, Pentosidine, etc.

・Serum: PINP, TRAP, NTX, CTX, Osteocalcin, bone-type ALP, Homocysteine, Pentosidine, Sclerostin, etc.

 

Type II Collagen-Induced Arthritis Model

Collagen-induced arthritis is a disease model known to be immunologically and clinically similar to rheumatoid arthritis. Arthritis (swelling of the phalangeal joints) is induced in female cynomolgus monkeys by sensitization with bovine type II collagen, and evaluated to determine the therapeutic or preventive effects of the test article. The evaluation is mainly carried out by the temporal measurements of the swelling score and X-ray score for the phalangeal joint. So, in consideration of action mechanism of test article, C-reactive protein (CRP), which is a marker of inflammation, and erythrocyte sedimentation rate (ESR) are measured. If necessary, antibody titer (IgM, IgG), blood chemistry, hematological and histopathological examination are performed. 

 

Parkinson's Disease Model

Intravenous MPTP/HCl dosing to male cynomolgus monkeys induces the expression of symptoms in the central nervous system which are similar to those found in manifestations of Parkinson's disease. MPTP administration is suspended when obvious symptoms are observed, and animals are selected after confirming LDOPA reactivity and the stable continuation, noted by scoring, of the condition of the central nervous system for about 2 months. The effectiveness of the test article is evaluated by the scoring of Parkinsonism (consciousness, mobility, coordination, posture, tremor, etc.).

 

Steroid-Induced Osteopenia Model

A decrease in bone mass is induced by repeated administration of steroid in rats. Effects of the test articles are evaluated by their effects on bone density and bone metabolism markers.

 

Acute Respiratory Distress Syndrome (ARDS)

A single intravenous dose of oleic acid is administered to dogs or cynomolgus monkeys to prepare a pulmonary edema model. Efficacy of the test article is evaluated by its effects on pulmonary function, inflammatory markers in serum and bronchoalveolar lavage fluid, and structural changes in the lung (histopathological examination and CT examination).

 

Glaucoma Model

Laser irradiation is applied to the entire circumference of the trabecular meshwork to prepare a glaucoma model with ocular hypertension in cynomolgus monkeys, and this model is used to evaluate the ocular hypotensive effect of the test article. We can take stabilized intraocular pressure measurements using conscious animals that have been acclimated to the measurement procedures. In addition to the ocular hypotensive effect, we are also investigating evaluations of the test article’s neuroprotective effects using optical coherence tomography (OCT) and MRI.

Choroidal Neovascularization (CNV) Model

 

In the age-related macular degeneration model, choroidal neovascularization is induced by laser irradiation to the macula of cynomolgus monkeys to evaluate the inhibitory effect on choroidal neovascularization. Fluorescein fundus angiography is used to evaluate the inhibitory effect of the test article on choroidal neovascularization. Quantitative evaluation with morphometrics for the lesion sites is also available; this evaluation uses image analysis software for each of the various tissue specimens, and tissue samples are prepared using a variety of staining methods, such as special staining and immunostaining. In addition, in optical coherence tomography (OCT) image and fluorescein fundus angiograph, we also carry out quantitative and temporal evaluation using image analysis.

Fluorescein fundus angiography in the cynomolgus CNV model
Fluorescein fundus angiography in the cynomolgus CNV model

 

Cerebral Infarction Model

The middle cerebral artery is occluded by injecting autologous thrombi from a catheter that is surgically placed in the left internal carotid artery in cynomolgus monkeys. Neurological impairment is observed, such as clouding of consciousness or contralateral sensory-motor paralysis occurring immediately after the occlusion. The evaluation of cerebral infarction is based on neurological impairment and TTC staining. 

 

Spontaneous Hyperuricemia Model

Capuchin monkeys have high uric acid compared to other primates. The ability of the test article to lower uric acid is evaluated by measuring uric acid, xanthine, and hypoxanthine.

 

Learning and Memory Function using CANTAB

Animals are used that have been pre-trained in the delayed matching to sample task using a touch screen recognition learning device for primates (Monkey CANTAB) and that have maintained a high rate of correct answers (primarily rhesus monkeys). Transient memory impairments are caused using drugs such as scopolamine, and we evaluate whether test article administration improved the learning and memory impairments. 

 

Noxious heat Stimulation-Induced Pain Model

The time for monkeys to raise the tail when the tail is immersed in a hot bath (Tail Withdrawal Latency, TWL) is used as an index to evaluate the analgesic effect of the test article on noxious pain.

 

Capsaicin-Induced Allodynia Model

Allodynia is induced by subcutaneously administering capsaicin to the tail of rhesus monkeys. Tail Withdrawal Latency is used as an index to evaluate the analgesic effect of the test article.