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Pig Model Validation In Neuropathic Pain-SfN 2015

Posted by MD Biosciences on Oct 30, 2015 3:31:09 PM

Last week, MD Biosciences presented a poster at the Society for Neurosciences 2015 Conference in Chicago. As strong advocates for the use of pig in translational neuropathic pain research, we introduced a new pig proximal peripheral neuritis trauma (PNT) model that shares many similarities in morphological and molecular pathologies with skin biopsies from human pain conditions. This is particularly true in comparisons with patients suffering from persistent area pain conditions such as postherpetic neuralgia (PHN) and complex regional pain syndrome (CRPS) as well as other chronic pain conditions.

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Topics: Pain, Neuro/CNS, Stress, trauma pain, pain biomarkers, CNS imaging, Imaging

Stress, Trauma & Pain- Image Not Imagine The Evidence| Biomarkers

Posted by MD Biosciences on Sep 11, 2015 10:00:00 AM

 The 9th Annual Congress of the European Pain Federation EFIC® was anything but painful as it concluded last week in Vienna with three days of riveting talks. The speakers consisted of expert pain practitioners, scientists, and policy makers who came together with the goal of “translating evidence into practice”.

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Topics: Pain, Neuro/CNS, EFIC 2015, Stress, Imaging, European Pain Federation

Targeting Microbiomes & Biomarkers: Inflammation World Congress

Posted by MD Biosciences on Aug 20, 2015 3:30:00 PM


The 12th World Congress on Inflammation wrapped up on Wednesday August 12th after four days packed with cutting edge inflammatory research by key opinions leaders in the field. Presentations hit every aspect of the scientific spectrum from development of pre-clinical models through retrospective studies on new target therapies and everything in between. Highlights of the conference included the Keynote Lecture by Luke O’Neill of Trinity College Dublin, the Symposium “Mechanisms Underlying Microbiome-Mediated Inflammation”, and multiple discussions on identifying and targeting novel biomarkers of inflammatory diseases.

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Topics: Inflammation, metabolic, Preclinical Discovery, Microbiome, Biomarkers, World Congress on Inflammation

The Pathology of the IL-33/T1/ST2 Pathway: Harmin’ Alarmin

Posted by MD Biosciences on Aug 10, 2015 4:30:00 PM

IL-33 is a member of the IL-1 cytokine family that is expressed constitutively in the nucleus of epithelial and endothelial cells as well as in CNS oligodendrocyte and astrocyte cells (1-2). Its release in response to cell damage and/or death has earned it the classification of “alarmin” – an immunological alarm signal that is released in times of cellular distress (3-4). Upon release, IL-33 binds to the T1/ST2 and IL-1R accessory protein (IL-1RAP) heterodimer complex to activate the MYD88-dependant signaling pathway (1).

Studies targeting the function of IL-33 and/or signaling through its T1/ST2 receptor have highlighted the dual role this versatile cytokine pathway plays in the induction inflammatory immune reactions. More interestingly, these reactions can be either beneficial or pathological in nature. Here we will discuss the pathological role of IL-33 in disease.

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Topics: Dermal, Inflammation, Research Products, Infection, Acute Kidney Injury (AKI)

Successfully Predict Neuropathic Pain Conditions

Posted by MD Biosciences on Jun 29, 2015 11:21:00 AM

The rodent has historically been used as the dominant model for the study of pain mechanisms and new therapeutics. There are good reasons for this such as the practicalities and ease of use with small animals as well as the scientific value of having a large database of prior research for predictive validity. The rodent models will continue to be the workhorse driving research and drug discovery, however there is a large failure rate of drugs moving into clinical stages, which failure of rodent models to predict the biology of the clinical condition certainly plays a role. The most well known example of this is the NK1 antagonist that exhibited efficacy-related translational failure in the clinic.

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Topics: Neuro/CNS

Novel Biomarkers| Detecting early-stage Acute Kidney Injury (AKI)

Posted by MD Biosciences on May 7, 2015 10:47:16 AM

Acute kidney injury is a disease that is characterized by a rapid loss of kidney function, including the rapid fall in glomerular filtration rate (GFR) and the retention of nitrogenous waste over the course of hours and days. AKI is a complex, multifactorial disease with inflammatory, ischemic, necrotic and apoptotic events that occur simultaneously, leading to damage and functional kidney failure. The process of kidney injury occurs in stages starting with increased risk, followed by damage as a result of ischemic injury or toxicity, followed by a decrease in glomerular filtration rate (GFR), which further progresses to kidney failure.

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Topics: Acute Kidney Injury (AKI)

Drug Discovery Success Rates | Role of Preclinical Study Design.

Posted by MD Biosciences on Apr 22, 2015 12:16:55 AM

In 2014, an article was published in Nature analyzing the clinical development success rates for investigational drugs. It's no surprise that the success rates are still somewhat dismal with 1 in 10 drugs that enter clinical phases pushing through to FDA approval. The article breaks down the success rate in each phase for differing classes of drugs as well as various therapeutic indications. NMEs were found to have the lowest success rates in every phase of development (7.5%) whereas biologics had nearly two times the success rate (14.6%).

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Topics: Preclinical Discovery

Translating Preclinical Data to the Clinic

Posted by MD Biosciences on Mar 24, 2015 1:07:37 PM

It's a question that comes up regularly, from scientists who contact us to publications to conference lectures. One of the challenges in preclinical drug discovery is how translatable is the preclinical data from animal studies to the human situation?

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Topics: in vivo pain models, Preclinical Discovery

The Value of Phenotypic Screening

Posted by MD Biosciences on Mar 24, 2015 11:21:23 AM

Preclinical strategies used to identify potential drug candidates include target-based screening, phenotypic screening, modification of natural substances and biologic-based approaches. In the earlier days of drug de- velopment, phenotypic screening was largely employed and identified molecules that modify a disease phe- noytpe by acting on a previously unidentified target or simultaneously on more than one target. In the 1980s, advances in molecular biology and genomics led to a shift in developing compounds against defined targets that were implicated in disease. The success rate of clinical stage candidates, however has not improved and phenotypic screens are coming back into light. 

In a recent publication, analysis of different discovery strategies for 259 approved new molecular entities (NMEs) and new biologics between 1999 and 2008 showed that the contribution of phenotypic screening to the drug discovery of first-in-class small molecule drugs exceeded that of target-based approaches in an era when the major focus was on target-based approaches (Swiney, D and Anthony, J. Nature Rev. Drug Disc. (2011) 10:507-519). 

 

Phenotypic Screening gets another look?

While phenotypic screening is getting a second look and making its way back into some biopharma's discovery toolbox, many phenotypic screens are established on the basis of cellular systems or systems that are set to ‘mimic’ the in vivo environment. These systems range from a simple single cell types to more complex cell or tissue systems. What can occur with in vitro phenotypic screens that aim to mimic the in vivo environment is:

  • The screen is most often selectively look at single pathways and therefore miss inter-pathway interactions

  • The screens, while aiming to mimic the in vivo environment, don’t predict the in in vivo effect and unexpected biology, interactions or potential toxicity effects that are often observed in vivo.

  • Can miss pharmaceutical candidates whose pharmocology isn't evident until it is in a complex biological system.

This has led us to develop a more comprehensive, in vivo phenotypic screening platform, Senerga®. The Senerga® Phenotypic Screening platform consists of a series of matrices designed to cover maximum biological pathways to identify pharmaceutically relevant candidates that also show no predictive toxicity effects early on in the discovery process. This enables researchers to move beyond well-defined targets from the literature or their existing programs and discover new disease biology and potential targets.  

The benefit to using this powerful screening program:

  • Enables researchers to see effects on disease phenotypes in a complex biological setting with multiple pathways involved.
  • Obtain predictive toxicology data at the same time.
  • Expands therapeutic potential of libraries as it covers maximum biological pathways with biomarkers to support potential mechanisms
  • Identify hits relatively quickly that can be put through further target validation or efficacy proof of concept studies. 

With the need to move quickly and fill drug discovery pipelines with new candidates, this phenotypic screening platform is designed to efficiently screen compound libraries rapidly (within 3 - 9 months dependent on the size of the library). The resulting data is mined for hits that are identified from modified disease phenotypes and biological pathways. If you'd like to speak with a scientist about utilizing the Senerga® Phenotypic screening platform, please fill out the following details and a scientist will be in contact with you. 

 

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Assessing Subjective Pain | Preclinical Pain Studies

Posted by MD Biosciences on Feb 19, 2015 10:57:04 AM

Rodent models of pain such as nerve injury models are important to understand the mechanisms that may contribute to human neuropathic pain. Imaging studies in human have identified cortical regions specifically involved in the subjective, conscious perception of pain. Although laboratory animals process painful stimuli using similar mechanisms and thresholds of awareness as humans, it is much harder to assess the subjective pain experienced by animals as they can not self-report. This has led researchers to rely on objective measures of pain-related behaviors such as evoked responses to noxious stimuli. Humans, however, are able to voice discomfort, which provides rapid and direct access to the subjective experience. 

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Topics: in vivo pain models