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Efficacy Studies

Gwathmey Preclinical Testing Services focuses our efficacy studies in three therapeutic areas. Please inquire about therapeutic areas not listed. Please click on the one in your area of interest. You will also find a list of our thought-leaders in these fields. For a complete list of scientific advisors, please see our Scientific Advisory Board

Cardiovascular Disease

Thought Leader: Roger J. Hajjar, MD

Heart failure is the number one killer in the developing world. Over $243 billion dollars is spent each year in the treatment of heart failure. Although more people are surviving their first myocardial infarction, they nevertheless go on to develop overt heart failure. As a result, the incidence of heart failure is increasing.

Gwathmey Preclinical Testing Services, Inc. offers unique in vivo models of cardiovascular disease enabling compounds to be tested for effect on heart contractility.

Avian Model of Dilated Cardiomyopathy (DCM): Dilated cardiomyopathy is induced in turkey poults by feeding a high concentration of a growth promoter. The development of this model was supported by the National Heart, Lung and Blood Institute (NHLBI) because of a high level of congruence with the human condition.

Alcohol Induced Cardiomyopathy (AHF): Animal models of alcohol induced heart disease typically do not develop overt heart failure. Gwathmey Preclinical Testing Services, Inc. has developed an AHF model supported by the National Institute of Alcohol Abuse and Alcoholism (NIAAA).

Myocardial Infarction Models: Myocardial infarction is induced via permanent occlusion of the left descending coronary artery (LAD) in rodents, guinea pigs, and rabbits.

Occlusion and Reperfusion Model: A model of ischemia reperfusion injury based on the temporary occlusion of the LAD, inducing ischaemia in part of the left ventricle. Reperfusion can be initiated by removing the occlusion.

Pressure Overload Induced Cardiac Hypertrophy Model: A well-characterized and highly reproducible model where hypertrophy is induced by banding the ascending aorta. This model is used to evaluate the development of left ventricular hypertrophy in response to hemodynamic stress. The model also transitions to overt heart failure.

Echocardiography: Applications of transthoracic echocardiography to define differences in LV function between normal rodents and transgenic rodents having altered myocardial contractility have been possible with new ultrasound probes.  More recently echocardiography has allowed the assessment of quantitative differences between morphological and functional cardiac phenotypes in vivo.  Accordingly, the utility of echocardiography has increased tremendously for detecting abnormalities of LV chamber size, LV wall thickness, and LV mass and function in rodent and surgical rodent models of cardiac disease. 

Hemodynamics: Gwathmey Preclinical Testing Services, Inc. , has extensive expertise with both the telemetered device as well as Millar pressure volume recordings in conscious rodents. In particular, catheters now exist to simultaneously measure ventricular blood pressure as well as conductance (volume).  Millar Instruments has developed such a pressure-volume catheter, which has emerged as the gold standard for both invasive and minimally invasive cardiac function studies. 

Telemetered Arterial Pressure/ECG system/Body Temperature (GLP/non-GLP): With current telemetered systems it is only possible to measure arterial blood pressure, body temperature, and ECG simultaneously.  Due to technology limitations they are not able to measure ventricular pressures nor can they measure ventricular volume. 

Langendorff: Gwathmey Preclinical Testing Services, Inc. offers drug screening services for cardiotoxicity using the Langendorff heart model. Isolated perfused hearts allow you to control preload and afterload on the heart thereby influencing myocardial contractility. The heart rate can be controlled by pacing. Therefore, the isolated perfused hearts allows evaluation of the heart devoid of the complication of changes in systemic hemodynamics.

Cardiac Myocyte: Gwathmey Preclinical Testing Services, Inc. offers myocyte isolation services. Direct cardiac myocyte effects devoid of hemodynamics, load, and matrix interactions can best be studied in isolated cardiac myocytes. Negative impact on the cardiac myocyte can be easily detected e.g. arrhythmogenesis, apoptosis or cell death. Positive or negative inotropic effects can also be easily detected in the extent and rate of myocyte shortening (+dP/dt and –dP/dt, peak shortening, end diastolic length).  The shortcoming of isolated myocytes is that they are not under physiological load.

Cardiovascular Surgical Techniques:

  • Gene delivery, plasmid, or stem cell delivery to the heart (e.g. coronary delivery or intramyocardial injection).
  • Cannulation of carotid or femoral arteries or jugular vein.
  • Catheter insertion: left ventricular, femoral artery, carotid artery and jugular vein.
  • Aortic banding and myocardial infarction
  • Vessel injury

Oncology

Thought Leader: Henry Koon Jr., MD

Over one million people get cancer each year. Approximately one out of two American men and one out of every three American women wil have some type of cancer at some point during their lifetime. Anyone can get cancer at any age; however, about 77% of all cancers are diagnosed in people age of 55 and older.

Gwathmey Preclinical Testing Services, Inc. offers animal models for oncology studies enabling the evaluation of new chemotherapeutic or immunotherapeutic agents, drug regimens, or other modalities of treatment. These models can also yield further insight into basic mechanisms of tumor growth and spread.

Xenograft Nude Mouse Model: A versatile model where tumors are propagated in vivo in athymic nude mice from cancer cells grown in vivo or in vitro.

Metastatic Disease Models: Syngenic murine cancer cell lines are injected into immunocompetent mice for tumor generation, serving as a model of metastatic disease.

Chemically Induced Models: Carcinogen-induced tumor growth induced via injection of toxic compounds.

Specialized Tumor Models: Specialized customer specific tumor models and protocols can be implemented.

Cell lines in-house:

  • MCF-7    Breast
  • HT-29    Colon
  • Panc-1   Pancreas
  • PC-3      Prostate

*Other cell lines may be requested.

Infectious Disease

Thought Leader: Kathryn Eaton, DVM, PhD

Infectious disease is a disease caused by a biological agent (e.g. virus, bacterium or parasite).

Gwathmey Preclinical Testing Services, Inc. offers high thoughput in vivo screening for lead compounds and New Chemical Entities (NCEs), as well as mutant strains to test drug resistance.

Septicemia Model: Gwathmey Preclinical Testing Services, Inc. has established a high throughput screening method (i.e. 3 days) for this model. This model has been shown to correlate closely to pharmacokinetic data. The end point is rate of survival.

Pharmacokinetics
Pharmacokinetics
Pharmacokinetics