MD Biosciences Blog

MD Biosciences Develops Large Animal Neuropathic Pain Model

Posted by MD Biosciences on Oct 3, 2012 6:48:00 AM

The porcine sciatica model can evaluate efficacy and PK/PD from the same subject and may provide more clinically relevant data at preclinical stages minimizing expensive failures.

MD Biosciences has developed a large animal model of neuropathic pain for preclinical evaluation of analgesic or neuroprotective therapies. The sciatica model was developed in the pig, as the innervation is similar to that of humans, providing more clinically relevant data at the preclinical stages. The model is suitable for evaluating both efficacy and PK/PD in the same animal and can be used for systemic, local and cell therapies as well as slow release drugs and devices.

Creating injury directly on the sciatic nerve by either nerve crush or nerve cutting induces neuropathic pain and minimizes the inflammatory component. The nerve crush method produces a less pronounced pain as well as a quicker recovery for the subjects. For therapies that are thought to be neuroprotective or promote nerve regeneration, partial nerve damage using the nerve crush method will allow direct treatment to the nerve. Using either method, subjects are completely recovered by 7 days post surgery and can be evaluated for pain up to 21 days. In addition to sensitivity to pain and pain sensation, subjects avoid using the ipsilateral leg suggesting a responsiveness to weight bearing and sustained pain.

 

Readouts:

  • Von Frey
  • Cold allodynia
  • Pin prick
  • Weight bearing
  • Histology

 

Pain threshold in the large animal model of neuropathic pain

Figure: Subjects underwent either nerve crush or nerve cut methods. Subjects were tested for sensitivity to Von Frey pre- and post-treatment with 1 mg/kg morphine. Data is reported using Von Frey method and shows the 50% threshold in grams (g). 

 

The porcine sciatica model of neuropathic pain is just one of many large preclinical models offered by MD Biosciences. With the high failure rate at clinical trial phases, more relevant preclinical models are needed to assess candidates at earlier stages. The pig is an ideal model system due to its human similarities in innervations, skin and the cardiovascular system. Other porcine models offered by MD Biosciences include post-operative pain, myocardial infarct, diabetes and diabetic neuropathy.

 

About MD Biosciences

MD Biosciences is a Preclinical and Clinical Contract Research Organization (CRO) providing services for biotech/pharmaceutical, medical device and animal health. Our core therapeutic focus is in inflammation/autoimmune, neurology/CNS disorders, pain and cardiovascular as well as the interplay between the inflammatory, neurology and cardiovascular systems. Our approach is to work backwards from the clinic, understanding what the clinicians would expect from an active compound. This approach and understanding enables the development of models and biomarkers that help break the preclinical/clinical barrier and provide more clinically relevant data at earlier stages.

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The information in this press release should be considered accurate only as of the date of the release. MDB has no intention of updating and specifically disclaims any duty to update the information in these press releases.

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Topics: Pain

3D Human Skin System w/Co-Cultures & Vasclr tech. Closely Resembles Human Skin

Posted by MD Biosciences on Jul 31, 2012 9:29:00 AM

MD Biosciences, in collaboration with Fraunhofer IGB, announces a revolutionary, in vitro 3D human skin equivalent (HSE) system. The model enables scientists to measure the penetration, resorption, metabolism and epidermal impedance in a human skin equivalent system Penetration across the layers is visible, enabling the determination of intracellular drug transport. The system offers two uptake routes for drugs:

  • Direct uptake by cells following topical administration
  • Deposition in skin cells following administration of drug through vascular system

The 3D HSE is a two-layered structure closely resembling natural human skin. The dermis layer is composed of dermal fibroblasts, embedded in a biomatrix consisting of tissue-typical matrix proteins. This serves as a scaffold for epidermal keratinocytes seeded on them. The keratinocytes differentiate into a multilevel epidermis with Stratum basale, Stratum spinosum, Stratum granulosum and Stratum corneum. Due to the interaction of fibroblasts and keratinocytes between the dermal and epidermal sections of the skin model, a functional basal membrane consisting of matrix proteins is developed. 

3D human skin equivalent system with co-cultures and vascularized technology, preclinical in vitro CRO

 

Additionally, the HSE system can be vascularized using BioVaSc technology:

  • De-cellularized jejunum for the appropriate scaffold material
  • Tubular structures are seeded with microvascularized endothelial cells leading to the synthesis of extracellular matrix including capillaries
  • Uniform tissue is made with no separation of layers or shrinking of skin enabling longer cultures

The vascularized 3D HSE system serves as an important advancement in the area of skin equivalents for use as a drug development tool. It eliminates many of the challenges associated with other commercially available skin equivalents such as low barrier properties, skin shrinkage due to inefficient scaffolds, short term culture limitations and lack of blood vasculature. By incorporating tissue-specific cells, the technology can be applied to multiple areas beyond skin such as infections, wounds, tumors and organs. To discuss how this technology can advance your particular program, contact MD Biosciences.

 

About MD Biosciences

MD Biosciences is a Preclinical and Clinical Contract Research Organization (CRO) providing services for biotech/pharmaceutical, medical device and animal health. Our core therapeutic focus is in inflammation/autoimmune, neurology/CNS disorders, pain and cardiovascular as well as the interplay between the inflammatory, neurology and cardiovascular systems. Our approach is to work backwards from the clinic, understanding what the clinicians would expect from an active compound. This approach and understanding enables the development of models and biomarkers that help break the preclinical/clinical barrier and provide more clinically relevant data at earlier stages.

 

About Fraunhofer IGB

Fraunhofer IGB develops and optimizes processes and products in the fields of medicine, pharmacy, chemistry, the environment and energy. Fraunhofer combines the highest scientific quality with professional expertise in fields of competence always with a view to economic efficiency and sustainability. Fraunhofer IGB is one of more than 80 research units of the Fraunhofer-Gesellschaft, Europe’s largest non-profit organization for application-oriented research. Fraunhofer IGB has obtained a patent for the three-dimensional human skin equivalent (patent ID: EP 1 290 145 B1) and in 2009 developed the biological vascularized matrix (BioVaSc) winning a technology prize for “human-centered” technology by the Fraunhofer-Gesellschaft.

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The information in this press release should be considered accurate only as of the date of the release. MDB has no intention of updating and specifically disclaims any duty to update the information in these press releases.

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Topics: Dermal

Preclinical Imiquimod-induced Psoriasis-like Skin Inflammation Model

Posted by MD Biosciences on May 1, 2012 2:12:00 PM

A Rapid 10 day preclinical efficacy study that produces lesions highly representative of human psoriatic lesions.

Wednesday, May 2, 2012, St. Paul, MN – The most common models for evaluating skin-related inflammation are time consuming and expensive. While they provide valuable data, they don’t allow for rapid and cost effective evaluation of therapeutics earlier in the preclinical pipeline. In response to this need for more convenient and cost effective models, researchers (Van der Fits et al, 2009) developed a model using Imiquimod (IMQ) to induce psoriasis-like inflammation.

Imiquimod is a potent immune activator that is traditionally used to treat virus-associated skin abnormalities and precancerous skin lesions. However it can exacerbate psoriasis (both at the treated area and at distant skin sites) during topical treatment. Application of IMQ to mouse skin results in the influx of various cells of the immune system as well as hyperplasia of the epidermis that is critically dependent on IL-23 and IL-17.

MD Biosciences now offers the IMQ-induced model of skin inflammation as part of its portfolio of efficacy services. The model is 10 days long and the lesions closely resemble that of human psoriatic lesions with erythema, skin thickening and epidermal alterations such as acanthosis and parakeratosis. Subjects are given a psoriasis score depending on the degree of erythema, scaling and thickening. Analysis includes clinical score of the back, ear thickness and histology of both the ear and back.

 

Image: histology on psoriatic lesions (B-D) compared to that of a naive sample (A) in the IMQ-induced model of skin inflammation. For additional data, please visit the IMQ-induced model.

histology of the skin in the IMQ-induced psoriasis-like model of skin inflammation, preclinical CRO

 

About MD Biosciences

MD Biosciences is a Preclinical Contract Research Organization (CRO) providing services and products for biotech/pharmaceutical, medical device and animal health and companies engaged in inflammations & neurology research. With specialized laboratories located in Minnesota, Glasgow, and Israel, our panel of internationally recognized experts provides in-depth expertise and technologies to overcome challenges and provide total solutions to the drug discovery market.

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The information in this press release should be considered accurate only as of the date of the release. MDB has no intention of updating and specifically disclaims any duty to update the information in these press releases.

Read More

Topics: Dermal