MD Biosciences Blog

St Paul, MN  – MD Biosciences announces that it has entered into a research agreement with one of the Top 10 pharma companies for screening a library of compounds. MD Biosciences will apply its innovative screening platform, Senerga®, to the pharma company’s compound library with the primary objective of increasing the chances of discovery efficacy on a broader and more efficient basis. These compounds can then be selected based on pharmaceutically relevant activity to be further developed by the sponsor.

 “Exploring novel, high-value applications for compounds based on our Senerga® Platform is the core strength of MD Biosciences. We are very excited about this compay engaging MD Biosciences in this important program. It is a great company, sharing our vision in evolving new and efficient ways in the discovery process” said Eddie Moradian, CEO of MD Biosciences.

About the Senerga® Screening Platform

MD Biosciences has a long history of working on complex programs for mechnism of action screening, and efficacy. By conceptualizing a platform that provides algorithmic analysis of a combination of efficacy, biomarker, mechanistic and safety/behavior data, clients are able to broadly screen compounds on the basis of effects on cells, tissues and whole organisms in disease modification without the necessity of prior knowledge of therapeutic pathways. Senerga® screening is a customized approach through in vitro and in vivo models selected to give the broadest screen based on the compound library.

About MD Biosciences

MD Biosciences is a global preclinical research group and contract research organization (CRO) working with biopharmaceutical and medical device companies in an effort towards progressing discovery and development programs to clinical stages. MD Biosciences provides a broad range of services focused in inflammatory, neurodegenerative/CNS, pain, dermal, metabolic and cardiovascular conditions with a particular emphasis on the interplay between the immune, nervous and cardiovascular systems and the conditions that arise in the cross talk between them. Utilizing innovative approaches to efficacy and screening models, MD Biosciences has played a key role for our clients in multi-year programs that have involved respositioning/developing compounds, out-licensing compounds and screening compound libraries. MD Biosciences diverse portfolio of clients includes some of the world’s largest and most well-known pharmaceutical and biotechnology companies.

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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.

MD Biosciences releases a new line of in vivo syngeneic tumor models for the study of primary orthotopic tumors and metastasis. The basis of the syngeneic tumor model is that it uses tumor cells that are injected into either the organ of origin or into the systemic circulation of a host that is of the same species and genetic background as the tumor cells or tissue originated from. Additionally, syngeneic tumor models offer the advantage of a short latency time and increased phenotype reproducibility due to injecting a controlled number of cells.

Syngenic tumor models are excellent preclinical models for studying the interaction of tumor cells with the host immune system as well as the impact of tumors on local and systemic factors such as the surrounding tissue and the vascular system. They utilize injected tumor cells or tissue from the same species and genetic background as the host, which permits the assessment of compatible tumor-stroma microenvironmental interactions, endocrine signaling and immune responses. Unlike xenotransplantation models where the hosts are immunocompromised to enable the innoculation of human tumors or cells into murine hosts without rejection, syngenic tumor models utilize immuocompetent hosts allowing immune-cell-tumor-cell interactions. This is critical as a functioning immune system is the backbone of studies involving cytotoxic T cells, Tregs, tumor-associated macrophages, cell trafficking or inflammatory fibrotic stromal reactions. Additionally, the effects of an intact immune system on the onset of metastasis and progression are important.

Orthotopic Tumor models are created on the basis of injecting tumor cells directly into the organ of origin and exhibit organotypical interactions between the tumor cells and the surrounding stroma. These interactions affect the growth, differentiation and drug sensitivity of the tumor cells.

• Breast Cancer
• Liver Cancer/Hepatocellular carcinoma (HCC)
• Neuroblastoma
• Pancreatic Cancer

Metastasis Models are created on the basis of injecting tumor cells directly to the systemic circulation. The site of injection will largely dictate which metastasis will develop as the cells will arrest in the first capillary bed encountered.

• Pulmonary metastasis
• Hepatic metastasis

MD Biosciences research group is actively involved in developing approaches, methods and models that bring greater translational relevance to the clinical situation. With a high failure rate in the clinical trial phase of drug development, more relevant models are needed that provide greater translation to the clinic.

About MD Biosciences

MD Biosciences is a leading preclinical research group and contract research organization (CRO) working with biopharmaceutical and medical device companies in an effort towards progressing discovery and development programs to clinical stages. We are deeply focused on inflammatory, neurodegenerative/CNS, pain, dermal, metabolic and cardiovascular conditions with a particular emphasis on the interplay between the immune, nervous and cardiovascular systems and the conditions that arise in the cross talk between them. We bring decisive value to preclinical programs with the extensive experience gained over many years of handling different compound classes through all administration routes aimed at numerous therapeutic indications.

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

MD Biosciences article Characterization of a porcine model of post-operative pain (POP) has been published in the European Journal of Pain, Sept 2013. Dr Sigal Meilin, lead neurologist and research director at MD Biosciences, participated in developing a porcine model of post-operative pain that we propose provides greater translational relevance for the evaluation of local treatments of POP compared with existing rodent models  of incisional pain. 

While the rodent model is commonly used for evaluating POP, one of the major disadvantages is that it is limited in its use in assessing topical and localized treatments such as devices or patches as the hindpaw is relatively small and the rodent may lick or bite at the injured paw. The rodent skin is also very different from human skin in that it heals primarily through contraction rather than re-epithelialization. Pigskin exhibits a higher degree of homology to human skin and has considerable correlation between contractile, metabolic and morphological features in skeletal muscle of human and pig. This model as has three important parameters that can be assessed in parallel:

• Nociceptor sensitivity
• Spontaneous behavior
• Wound healing and inflammation

The following abstract is from the publication in European J Pain, Sept 2013:

MD Biosciences focuses on rapid and cost effective models of psoriasis involving the IL-23/TH17 axis in order to provide companies alternatives to complex and costly xenotransplantation models for screening. With the earlier launch of the IMQ-induced model and now the IL-23 psoriasis model, MD Biosciences offers a range of rapid models for dermal conditions such as dermatitis and psoriasis. 

Recent psoriasis research has focused extensively on the IL-23/TH17 axis. While previously thought to be mainly a Th1 mediated disease, evidence has shifted to a new population of IL-17 producing Th17 cells and the involvement in a variety of autoimmune diseases including psoriasis. The development and maintenance of Th17 cells has been linked to IL-23, a key cytokine involved in the development of autoimmunity. With the focus of research on the IL-23/TH17 role in psoriasis, a number of novel therapeutics are currently in clinical trials that target this pathway.

MD Biosciences is currently working with a biopharmaceutical company in evaluating novel therapeutics that target this pathway. While models of psoriasis such as xenotransplantation models have traditionally been the most commonly used, they are complex and cost prohibitive for screening. MD Biosciences research group has validated rapid and cost effective preclinical models for screening psoriatic therapeutics. In addition to the IMQ-induced psoriasis model launched last year, the most recent model to be validated is the IL-23 induced model of psoriasisform inflammation.

The IL-23 psoriasis model is 21 days long and involves the injection of IL-23 into the ear of C57Bl/6, which produces psoriasis-like inflammation that is dependent on IL-22. IL-22 induces keratinocyte proliferation and epidermal hyperplasia contributing to epidermal thickening. “We are continually looking to the most recent research clinical findings. With the number of clinical trials involving targets in the IL-23/Th17 pathway, offering rapid preclinical models of psoriasis involving this pathway allows biopharma companies to cost-effectively screen potentially novel therapeutics. This is important for companies in early discovery to be able to evaluate compounds in a clinically relevant model of psoriasisform inflammation.”

Background on Th17 in psoriasis pathology

While the pathology of psoriasis is not completely understood, there are complex un- derlying mechanisms, which involve the interplay between epidermal keratinocytes, leukocytes such as dendritic cells and APCs, and vascular endothelium. Epidermal keratinocytes and vascular endothelial cells are active participants in the psoriasis inflammatory process via secreted cytokines and growth factors along with the upregulation of signaling and adhesion molecules on their surfaces. TGFb1 is elevated and released by keratinocytes, which when combined with activated dendritic cells is sufficient to generate TH17 cells in skin-draining lymph nodes inducing cutaneous inflammation. Intracellular signaling induces expression of IL-23R on developing Th17 cells promoting responsiveness to IL-23, the key cytokine in the survival and proliferation of Th17 cells. Th17 cells secrete a range of pro-inflammatory cytokines such as IL-6, IL-17A, IL-17F, IL-21, IL-22 and TNF-α . In psoriasis, IL-23 plays an important role with genetic alterations of IL-23p40 and IL-23R leading to enhanced IL-23 production increasing psoriasis susceptibility and indeed injection of the IL-17 supporting cytokine, IL-23, into the skin of mice can induce psoriasis-like inflammation. The main cellular source of IL-17A in psoriasis-like skin inflammation are γδ T cells located specifically in the dermal layers and expansion of Th17 cells producing inflammation and these cells are required to initiate the IL-23 driven processes.

About MD Biosciences

MD Biosciences is a Research Group and 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.

Nerve blocking agents are often used to replace general anesthesia in certain surgical procedures or for providing pain relieve in the post-operative period where the nerve block tends to provide more effect pain control and reduce opioid-related side effects. The rapid preclinical model of sciatic nerve block allows the screening of new nerve blocking agents or drugs designed to reverse the local analgesia. The surgical method employed with the nerve block model can also be applied to other models of pain where direct dosing to the sciatic nerve is desired rather than systemic administration.

The nerve block model is based on the administration of nerve blocking agents directly to the saphenous and sciatic nerves. Local injection is performed to the adductor canal as well as to the sciatic notch. Following the administration of nerve blocking agents, thermal hyperalgesia is tested for a duration relevant to the nerve blocking agent or drug being tested.

Review the surgical procedure and data for the model of nervel block.

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.