MD Biosciences Blog

Preclinical Pig Models for Therapeutic Studies

Posted by MD Biosciences on Nov 7, 2013 11:08:00 AM

Historically, rodent models have been used for the discovery of various biological mechanisms within disease states as well as preclinical development of therapeutics. Unfortunately there are many ways that the biology of rodents fails to accurately predict the clinical conditions of humans - this is particularly the case in pain therapeutics. This can be evidenced by the estimates that as many as 80% of all drug candidates across therapeutic areas fail in the most expensive stages of development - clinical trials. While the failures can be attributed to various reasons such as insufficient efficacy, unacceptable safety profiles or PK properties. With the high cost of developing new therapeutics, there is certainly the need to validate biological and pharmacological findings in models using larger species, which can also address some of the known differences between rodents and human. The pig is one species which may provide more translatable data to the human condition, particularly in therapeutic areas such as cardiovascular, skin or wound healing conditions, metabolic and pain.

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Topics: Dermal, Pain, CRO/outsourcing, Cardiovascular, metabolic

MMPs in ischemic conditions (stroke and myocardial infarct)

Posted by MD Biosciences on Jun 25, 2012 2:20:00 PM

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that function to degrade extracellular matrix. The turnover of ECM in organs is regulated by a balance by MMPs and their inhibitors (TIMPs) and the imbalance is implicated in a variety of diseases. Here we focus on the roles of MMPs in ischemia - particularly cerebral stroke and myocardial infarct.

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Topics: Neuro/CNS, Cardiovascular

Post Myocardial Infarct (MI) Inflammatory Environment

Posted by MD Biosciences on Jun 11, 2012 2:44:00 PM

At the tissue level, inflammation ensues very rapidly after myocardial infarct (MI), initially prompted by detection of high levels of reactive oxygen species (ROS) and necrotic cellular debris by resident cells in neighboring non-infarct tissues. ROS and necrotic cell debris are also detected by peripheral leukocytes, which home to the injured tissue, exit circulation, and infiltrate infarct and non-infarct tissues. Upon entering the lesion site, these leukocytes further release ROS, proteolytic enzymes, pro-inflammatory and cytotoxic diffusible factors and participate in phagocytosis of necrotic cells and disrupted ECM. This post-MI inflammatory environment in cardiac tissues peaks at 1 to 2 weeks and generally resolves at 3 to 4 weeks after the ischemic event. While important for clearing the tissue of compromised cells and debris and preparing it for transitioning into the proliferative phase of infarct healing, inflammation that becomes excessive or chronic results in adverse remodeling, infarct expansion, and poor patient outcomes. [1-4]

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Topics: Cardiovascular

Cardiovascular Disease & Underlying Inflammatory Events

Posted by MD Biosciences on May 10, 2011 2:51:00 PM

Cardiovascular disease (CVD) including heart disease, vascular disease and atherosclerosis are the most critical global health threats.

An estimated 26 million people are living with the effects of heart disease and is a major cause of death in western society. Until recently the widely held belief was that the CVD is simply the process as a build up of fat on the surface of artery walls. Eventually, this build up of fat blocks the artery and a heart attack or stroke occurs. However, the process has now been identified as a disease of the inner artery wall (intima) and inflammation is a key factor in its progression.

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Topics: Inflammation, Cardiovascular

Occlusion-induced ischemia Reperfusion Injury Model

Posted by MD Biosciences on Jun 16, 2010 10:35:00 AM

The preclinical occlusion-induced myocardial infarct model is a well-known technique for investigating the cardio-protection of a drug therapy in the event of ischemia/reperfusion injury. The advantage of the model is the ability to study the functional relevance of a drug treatment on the heart following direct coronary flow and the mechanisms by which the drug promotes myocardial protection.

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Topics: Cardiovascular