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MD Biosciences Blog

Suitable Preclinical Models Needed For Novel Asthma Treatments

Posted by MD Biosciences on Apr 6, 2011 11:08:00 AM

There is a major unmet need in the treatment of asthma which is growing in incidence and prevalence in industrialized countries. The prevalence of asthma has doubled in the Western world over the previous 20 years. In addition to the estimated 180,000 asthma related deaths per year, there is a substantial economic burden due to lost school/work days and increased medical costs.

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Topics: Inflammation

Pro-inflammatory Cytokines | Potential Neuropathic Pain Targets

Posted by MD Biosciences on Apr 4, 2011 1:06:00 PM

Over the past few weeks we have been reviewing the overlap between the nervous and immune systems. We recently discussed the various cell types involved and are going to move into some of the various inflammation related drug targets that may have potential involvement in neuropathic pain. We'll start with pro-inflammatory cytokines.

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Topics: Pain

T-cells in Rheumatoid Arthritis | Where, Why & When?

Posted by MD Biosciences on Mar 28, 2011 12:02:00 PM

The role of T-cells and their actions in rheumatoid arthritis (RA) has been the focus of a great deal of research for some time [1], mainly as a result of many observations in human patients and experimental animal models.  The association of Human Leukocyte Antigen (HLA) DR, a MHC class II cell surface receptor, in RA provides the strongest evidence that CD4+ T-cells are involved in the development of disease [2, 3, 6]. Many other types of T-cells, including CD8+, regulatory T-cells and γδ T-cells have been shown to play different roles in the progression of RA [1, 2, 3, 8]. The mechanisms of disease involved in RA are still unknown; however the main hypothesis theorizes that auto antigens are presented to auto reactive T helper cells, which then orchestrate the inflammatory processes which are characteristic of the disease [3]. The nature of the antigens involved is unknown however several candidates have been suggested, most recently, citrullinated proteins [5, 6].

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Topics: Inflammation

Cells Involvement|Neuro/Immune Interactions Along Pain Processing Pathway

Posted by MD Biosciences on Mar 15, 2011 2:19:00 PM

Previously we discussed various interactions that occur between the immune and nervous systems that are potential contributors to neuroinflammatory disorders. In this post, we will call out some of the specific cells involved in these interactions.

At the anatomical level, neuro‐immune interactions have been shown to take place all along the pain processing pathway. This is partially facilitated by increased permeability of the blood‐brain barrier following SCI or peripheral nerve injury [1]. At the cellular level, neuro‐immune interactions involve leukocytes including mast cells, neutrophils, macrophages, and T cells as well as glial cells with immunelike functions including Schwann cells and satellite glial cells in the PNS and microglia and astrocytes in the CNS. Alterations in glial cell function other than those associated with immune cells, immune system signaling molecules, or immune‐like functions of glial cells (i.e., alterations in neurotrophic factor signaling, potassium ion buffering, neurotransmitter re‐uptake, or gap junction maintenance) are outside the scope of this review and are not included here.

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Topics: Pain, Inflammation

Case study: 25 Preclinical CAIA studies, 18 months, 1 Out-licensed Compound

Posted by MD Biosciences on Mar 7, 2011 2:14:00 PM

With the number of blockbuster drugs approaching patent expiration and pharma companies struggling to maintain pipeline and portfolios with in-house programs, companies are increasingly turning to licensing, aquisitions and partnerships. Early-stage licensing deals tend to carry more risk for pharma companies in-licensing. To offset this risk, additional data may be required from the pharma partner to confirm any internal research performed by the biotech/out-licensing company.

Mini-case study. MD Biosciences helps a medium-sized biotech company to develop Rheumatoid Arthritis drug for out-licensing in under two years.

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Topics: CRO/outsourcing

Nervous & Immune System Interactions | Preclinical Targets

Posted by MD Biosciences on Mar 3, 2011 2:28:00 PM

Some of the most interesting and rapidly developing areas inbiomedical science are those being built between the lines previously drawn around classical fields of study. Neuroimmunology is jsut one of the many examples and is a field that is growing as researchers find interactions between the nervous and immune systems not previously known, and discover that some well-known disorders perhaps fall into this overlap category.

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Topics: Pain, Inflammation

Inflammatory Mediators & Neuropathic Pain Models

Posted by MD Biosciences on Jan 24, 2011 5:40:00 AM

Neuropathic pain is a chronic pain condition caused by lesion or inflammation affecting the nervous system. It is relatively common, can be severely debilitating and clinically significant relief is often difficult to achieve in part because conventional opioid therapy is typically less effective for neuropathic pain. The common symptoms of neuropathic pain include allodynia (pain resulting from normally innocuous stimulus), hyperalgesia (increased sensitivity to painful stimuli) and spontaneous pain. It has been widely known that a number of mechanisms are involved such as ectopic excitability of sensory neurons, altered gene expression of sensory neurons, and sensitization of neurons in the dorsal horn of the spinal cord. However, increasing evidence and research points to the interaction between the immune system and the nervous system playing a crucial role in the the underlying mechanisms of neuropathic pain (1). Following nerve damage, an inflammatory response is initiated: complement system is activated, a variety of inflammatory cells are recruited to the site of nerve injury, dorsal root ganglia (DRG) and to the spinal dorsal horn. Activation of immune-like glial cells   and an upregulation of inflammatory mediators all contribute to neuropathic pain (1-10).

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Topics: Pain, Inflammation

Pain & Inflammation Link | Need For Relevant Preclinical Models

Posted by MD Biosciences on Sep 15, 2010 2:12:00 PM

Considering the close link between inflammation and the pain process, preclinical efficacy models that allow the evaluation of both pain and inflammation are crucial to developing new therapies.

One of the prominent features of inflammatory conditions is that normally innocuous stimuli produce pain. The pain process involves several areas which include nociception, pain perception and pain behavior. After tissue injury or nerve damage, neurons along the nociceptive pathway may display enhanced sensitivity and responsiveness. A variety of events and agents can contribute to this sensitization, including the release of inflammatory mediators (such as cytokines or prostaglandins) or the release of algesic substances from damaged cells. Cytokines and prostaglandins are important mediators of inflammation that also have an effect on pain and nociceptors. Cytokines have influence over sensory neurons and may act directly upon nociceptors or indirectly by stimulating the release of prostaglandins, which are considered sensitizing agents and in some cases directly activate nociceptors.

What would efficacy and mechanistic models that allow you to evauate the effects on pain as well as the contributing inflammatory conditions mean for your therapy?

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Topics: Pain, Inflammation

EAE Preclinical Model Associated With FDA Approved MS Drugs

Posted by MD Biosciences on Aug 24, 2010 9:54:00 AM

The Experimental Autoimmune Encephalomyelitis (EAE) model is associated with FDA Approved MS Drugs and Fingolimod

Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that results in motor, sensory and cognitive impairment. MS is one of the most common disabling neurological diseases in young adults and is more prevalent in Caucasians of northern European ancestry. The disease course is unpredictable and life-long, and affects women more commonly than men.  The main characteristics of this disease are focal areas of demyelination and infiltration of inflammatory cells in the CNS. Despite numerous studies and experimental trials a complete understanding of the pathogenesis still remains unclear. The etiology of the disease seems to be dependent on genetic and environmental factors, which result in substantial observed variations throughout the course of the disease. Today, new treatments and medications are advancing hope for people affected by the disease, and the experimental autoimmune encephalomyelitis (EAE) model continues to play an essential role in MS drug development.

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Topics: Inflammation, Neuro/CNS

What PD in Vivo Models Revealed About Pathogenesis & Treatment

Posted by MD Biosciences on Aug 11, 2010 8:00:00 AM

Parkinson’s Disease (PD) is typically an adult-onset progressive neurodegenerative movement disorder that affects millions of people worldwide. Pathologically, PD is characterized by the profound and specific loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc) of the midbrain. Other areas interconnected with the SNpc, the caudate and putamen, collectively known as the striatum, also show remarkable loss of their projection fibers. In accordance with insult to brain regions involved in controlling coordinated movements, the cardinal symptoms of PD include bradykinesia, resting tremor, rigidity, and postural instability (1). To date, research into the etiology of
PD has revealed that most cases are sporadic, though some thirteen genetic loci have been identified to be disease-related (2). Examination of the biochemical properties of these mutant proteins and the pathways in which they are involved has led to the uncovering of three basic pathogenetic pathways common to both heritable and idiopathic forms of PD: (i) abnormal protein control, (ii) mitochondrial dysfunction, and (iii) altered kinase activity (2). Progress towards the identification of disease-related genes has thus led to the expansion of animal models of PD from the classic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- and 6-hydroxydopamine (6-OHDA)-induced neurotoxin models to genetic models of the disease. Due to its complex pathology, however, no animal disease model has yet to faithfully replicate all aspects of human PD. With the evolution of such models, though, converging lines of evidence from toxin-induced and genetic models have continued to further our understanding of the pathological processes underlying PD and lend themselves as useful systems for the examination of therapeutic interventions.

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Topics: Neuro/CNS