Scientific Research Partners

Preclinical efficacy testing in models of Lung Inflammation and Fibrosis

Lipopolysaccharide (LPS) Lung Inflammation/Acute Lung Injury Model
An acute model of pulmonary inflammation or lung injury induced by the administration of LPS. This is a rapid model where leukocytes (mainly neutrophils) are recruited to the lung within 4-6 hours of LPS treatment. This model allows for the measurement and characterization of the cellular profile of recruited leukocytes to the airways as well as the levels of pro-inflammatory cytokines within the lungs. LPS induces bronchoconstriction and/or bronchopulmonary hyperreactivity associated with inflammation when administered to rodents systemically or via the airways and this can be evaluated via pulmonary measurements.

Fluorescein isothiocyanate (FITC) Lung Inflammation/Lung Fibrosis Model
The administration of fluorescein isothiocyanate in rodents results in an acute inflammatory response characterized by a granulocytic infiltrate that progressed to chronic pulmonary fibrosis. This model displays histological similarity to human idiopathic pulmonary fibrosis. We have established a Respiratory Inflammation Panel (RIP) that provides information on the inflammatory potential of compounds at the biochemical, molecular, cellular, histological, and physiological levels. In this model SRP is also able to provide non-invasive and serial in vivo pulmonary evaluations. Treatment can be initiated at earlier or later time points to assess the effects of candidate agents on either aspect of this model.

Bleomycin Lung Inflammation/Lung Fibrosis Model
The administration of Bleomycin results in an acute inflammatory response characterized by a granulocytic infiltrate that progressed to chronic pulmonary fibrosis. This model displays histological similarity to human idiopathic pulmonary fibrosis. We have established a Respiratory Inflammation Panel (RIP) that provides information on the inflammatory potential of compounds at the biochemical, molecular, cellular, histological, and physiological levels. In this model SRP is also able to provide non-invasive and serial in vivo pulmonary evaluations. Treatment can be initiated at earlier or later time points to assess the effects of candidate agents on either aspect of this model.

Elastase Lung Inflammation/Lung Fibrosis Model
The administration of Elastase induces an acute lung inflammation which ultimately progresses to a state of emphysematous lung injury. We have established a Respiratory Inflammation Panel (RIP) that provides information on the inflammatory potential of compounds at the biochemical, molecular, cellular, histological, and physiological levels. In this model SRP is also able to provide non-invasive and serial in vivo pulmonary evaluations. Treatment can be initiated at earlier or later time points to assess the effects of candidate agents on either aspect of this model.

Preclinical efficacy testing in models of Pain

Inflammatory Pain Models
Widely used, the formalin test is a biphasic model of inflammatory pain resulting from formalin or carrageenan-induced tissue injury. It is a useful model, particularly for the screening of novel compounds, since it encompasses inflammatory, neurogenic, and central mechanisms of nociception.

Visceral Pain Models
The writhing test is a chemical method used as a model of visceral pain of peripheral origin by injection of irritant principles like phenylquinone and acetic acid. Analgesic activity of the test compound is inferred from decrease in the frequency of writhings.

Acute Pain Models
Experimental models of pain include tests of response thesholds to high intensity stimuli (acute pain tests). Acute thermal pain is modeled by either the hot-plate and tail-flick test.

Preclinical efficacy testing in Cardiovascular models

Spontaneously Hypertensive Rat (SHR)
The SHR model is an in vivo model of essential (or primary) hypertension, which develops heart failure with aging, similar to man. The consistent pattern of a long period of stable hypertrophy followed by a transition to failure provides a useful model to not only study mechanisms of heart failure with aging, but also lends itself for test treatments at differing phases of the disease process. The SHR model is the most studied model of hypertension measured as number of publications. The Spontaneously Hypertensive Rat (SHR) is also used as a model of attention-deficit hyperactivity disorder ADHD.

Preclinical efficacy testing in models of Diabetes

Non-obese diabetic (NOD) Model
Non-obese diabetic or NOD mice, are used as an in vivo model for type 1 diabetes. The Non-obese diabetic (NOD) mice exhibit a susceptibility to spontaneous development of autoimmune insulin dependent diabetes mellitus (IDDM). The widely used non obese diabetic (NOD) mouse model of autoimmune diabetes mellitus shares multiple characteristics with the human disease, and studies employing this model continue to yield clinically relevant and important information.

Zucker Fatty Rat (ZFR) Model
In the ZFR model the development of type 2 diabetes is of spontaneous origin involving genetic factors and the animals develop characteristic features resembling human type 2 diabetes.

*The STZ-induced Diabetes model is currently under development.

Preclinical efficacy testing in models of Asthma

Ovalbumin (OVA) Induced Allergic Asthma
Ovalbumin-induced allergic asthma is a widely used model to reproduce the airway eosinophilia, pulmonary inflammation and elevated IgE levels found during asthma. Studies can be run with or without airway hyper-responsiveness (AHR) measurements.

House Dust Mite (HDM; derp P) Induced Allergic Asthma
House Dust Mite-induced allergic asthma is a widely used model to reproduce the airway eosinophilia, pulmonary inflammation and elevated IgE levels found during asthma. Studies can be run with or without airway hyper-responsiveness (AHR) measurements.

Preclinical efficacy testing in models of Arthritis

Collagen Induced Arthritis (CIA)
In the CIA model both innate and adaptive immune mechanisms are involved. While no models perfectly duplicate the condition of human RA, they are easily reproducible, well defined and have proven useful for development of new therapies for arthritis, as exemplified by cytokine blockade therapies.

Adjuvant Induced Arthritis (AIA)
The AIA model was the original model of RA. After a single injection of the adjuvant, a rapid, reliable, robust and easily measureable polyarthritis develops. The AIA model has been used extensively to conduct preclinical screening of new anti-arthritis compounds and has successfully predicted activity and toxicity in multiple new therapeutics.

Preclinical efficacy testing in Oncology models

The following in vivo anticancer efficacy evaluations are available to assist our clients in advancing their pharmaceutical candidates.
• Human tumor xenografts in athymic nude or SCID mice efficacy models
• Customized Tumor Model Development for clients
• Early vs. late-stage disease and treatment comparisons
• Evaluations to maximize compound effectiveness
• Establishment of maximum tolerated dose
• Determination of minimum effective dose
• Determination of dosing schedule dependency
• Comparison of formulations and routes of dose administration

Preclinical efficacy testing in infectious disease models

The following in vivo efficacy evaluations are available with bacteria, fungi and certain toxins to assist our clients in advancing their pharmaceutical candidates.
• Development and refinement of efficacy models
• In vivo screening
• Efficacy testing