Cambridge Healthtech Institute’s seventh annual conference on PAIN: Novel Drug Targets and Screening Tools brings together leading experts, from industry, academia and government/regulatory agencies, to discuss the latest developments and trends in pain research. This year the conference will continue its focus on innovative drug targets including ion channels and GPCRs, while bringing attention to epigenetic and genetic modulators of pain. The increasing role of biologics will be discussed, as well as, novel screening technologies and animal models that are helping validate some of these new targets and inhibitors.
Day 1 | Day 2 | Pain Therapeutics Brochure | Speaker Biographies
Wednesday, May 21
7:00 am Registration and Morning Coffee
8:00 Chairperson’s Opening Remarks
Chair: Maree Smith, Ph.D., Executive Director, Centre for Integrated Preclinical Drug Development (CIPDD) & Professor of Pharmacy, The University of Queensland, Australia
8:05 New Approaches to NMDA Receptor Modulation: Glycine Site Functional Partial Agonists are Efficacious and Do Not Cause Psychotomimetic Effects
Ronald Burch, M.D., Ph.D., CMO, Research & Development, Naurex, Inc.
GLYX-13 and NRX-1074 are NMDA receptor Glycine Site Functional Partial Agonists. These agents both inhibit neuropathic pain (e.g. Chung model). In clinical trials, these agents do not cause psychotomimetic side effects, unlike previously studied agents such as ketamine that completely block the NMDA receptor ion channel. Dosing for 12 weeks in patients is not associated with reduction in efficacy. In animals, neither NMDA receptor glycine site functional partial agonist substituted for ketamine in drug discrimination trials.
8:35 Amelioration of Neuropathic, Inflammatory and Cancer Pain in Rodent Models With a Novel Brain-Penetrant Peptide-Neurotensin Conjugate
Jean Lachowicz, Ph.D., CSO, R&D, Angiochem, Inc.
The analgesic properties of neurotensin have been recognized for decades, but because the peptide does not cross the blood-brain barrier, its therapeutic utility is limited. We have created a conjugate of neurotensin and Angiopep-2, which is recognized by a receptor that mediates transcytosis across the blood-brain barrier. This An2-Neurotensin shows efficacy in rodent models of multiple types of pain when administered systemically.
9:05 CGRP Receptor Antagonists for the Treatment of Migraine
Ian Bell, Ph.D., Principal Scientist, Discovery Chemistry, Merck Research Laboratories
Calcitonin gene-related peptide receptor antagonists (CGRP-RAs) have demonstrated clinical efficacy for acute treatment of migraine. In general, these agents have shown similar clinical responses to triptans with a reduced incidence of adverse events. Interestingly, the precise mechanism of action of CGRP-RAs, in particular whether they act centrally or peripherally, continues to be a matter of debate. Our program to develop novel, orally bioavailable CGRP-RAs and our efforts to elucidate their site of action will be discussed.
9:35 Coffee Break in the Exhibit Hall with Poster Viewing
10:20 Angiotensin II Type 2 Receptor (AT2R) Antagonists as Novel Analgesics for Relief of Neuropathic Pain
Maree Smith, Ph.D., Executive Director, Centre for Integrated Preclinical Drug Development (CIPDD) & Professor of Pharmacy, The University of Queensland, Australia
Highly selective small molecule AT2R antagonists produce dose-dependent analgesia in rodent models of neuropathic pain, with analgesia abolished by genetic deletion of the AT2R. The analgesic mode of action involves attenuation of augmented angiotensin II/AT2R signaling in the dorsal root ganglia (DRGs) to block p38 MAPK and p44/p42 MAPK activation that are key enzymes in the phosphorylation of Nav1.7, Nav1.8, Cav2.2 and TRPV1, that are expressed in DRG neurons and are implicated in neuropathic pain.
10:50 The Role of Acid Sensing Ion Channels (ASICs) in Pain and Inflammation
Kathleen Sluka, Ph.D., Professor, Department of Physical Therapy and Rehabilitation Science, University of Iowa
Acid sensing ion channels (ASICs) are activated by decreased extracellular pH and are the primary acid-sensors in the nervous system. ASICs are found in nociceptors and play a significant role in inflammatory and non-inflammatory muscle pain. ASICs are also expressed on synoviocytes and regulate inflammation. The role of ASICs on nociceptors in transmitting inflammatory and non-inflammatory muscle pain, as well as the role of ASICs on synoviocytes in the regulation of inflammation will be presented.
11:20 Qube - High Throughput Screening with Genuine Electrophysiology
Richard Kondo, Ph.D., Head, Sales, North America, Sophion Bioscience
The Qube is a 384 channel, gigaohm-seal based automated patch clamp instrument for recordings from voltage-gated and ligand-gated ion channels. It offers the capability to screen large compound libraries for ion channel block or modulation. Data are obtained with a throughput of more than 30,000 wells tested per 24 hours.
11:35 Development of Cell-Based Assays for Pain Drug Discovery Using Native Sensory Neurons
Paul Karila, Ph. D., Vice President, Discovery Services, Cellectricon
Native cell types with relevance to pain drug discovery are being used by Cellectricon to develop assays with improved physiological relevance over traditional approaches. Progress towards high-throughput compatible assays using primary neuronal cultures will be discussed along with some examples of applying these cells for phenotypic screening.
12:05 Longitudinal MRI Studies in Rats: Mechanisms of Ongoing Pain and Development of Chronic Pain
David A. Seminowicz, Ph.D., Assistant Professor, Department of Neural & Pain Sciences, University of Maryland School of Dentistry
Studies using functional and structural MRI in rats can provide information about mechanisms of acute and chronic pain that cannot be easily assessed in humans. In this talk, I will describe our studies involving the longitudinal analysis of brain changes in central and peripheral neuropathic pain models in rats. In combination with longitudinal studies in humans, these designs can potentially be used to monitor the efficacy of various pain interventions.
12:35 pm Imaging Pain in Awake Rats: Applications in Preclinical Drug Discovery
Craig Ferris, Ph.D., Professor, Department of Psychology and Pharmaceutical Sciences, Director, Center for Translational NeuroImaging, Northeastern University
Functional Magnetic Resonance Imaging (fMRI) is a powerful and translatable technology used to study brain function and activity. In addition, the identification of imaging biomarkers independent of behavioral assays can be used to as an indication of pharmacodynamics and efficacy in the research and development of novel analgesics. We have employed the use of functional MRI in awake rats to assess changes in brain activity following challenge with a variety of pain stimuli in wild-type and transgenic rats with and without drug treatment.
1:05 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
1:35 Session Break
2:00 Chairperson’s Remarks
Chair: Edward Bilsky, Ph.D., Professor of Pharmacology; Vice President for Research and Scholarship, University of New England
2:05 Are We Making Progress in Developing and Validating Preclinical Animal Models of Pain and Analgesia?
Edward Bilsky, Ph.D., Professor of Pharmacology; Vice President for Research and Scholarship, University of New England
Significant attention has been focused on preclinical animal models, their use in understanding the neurobiology of human pain, and in their ability to predict analgesic efficacy in pharmaceutical drug development process. This session will examine the progress made to date in refining the models and how we measure the different components of pain and pain relief in animals, and how we can use these approaches to improve the drug development process.
2:35 A Novel Procedure for Research on Pain-Related Depression in Rats
S. Stevens Negus, Ph.D., Professor, Department of Pharmacology and Toxicology, Virginia Commonwealth University
Pain is often associated with depression of behavior and mood, and relief of pain-related depression is a common goal of treatment. We have developed a novel preclinical assay of pain-depressed behavior in rats, and we have used this procedure to examine expression, neurobiology and treatment of pain-related behavioral depression. Data will be presented to suggest a role for dysregulated mesolimbic dopamine signaling as a mediator of pain-depressed behavior and a target for treatment.
3:05 Thalamocortical Dynamics of Pain
Carl Saab, Ph.D., Assistant Professor, Departments of Neuroscience & Neurosurgery, Brown University and Rhode Island Hospital
Our lab is interested in electrophysiological biomarkers of pain. Our data show that spontaneous pain states in awake rats with acute or chronic pain are linked to increased power of theta oscillations in somatosensory cortex, and decreased synchrony between cortical and thalamic waveforms. Therefore, thalamocortical dynamics are potential pain biomarkers. On-going research in our lab aims at elucidating the cellular mechanisms underlying these observations, using multi-channel recordings combined with optogenetic neuromodulation.
3:35 Preclinical Assessment of Pain: Improving Animal Models in Discovery Research
Tamara King, Ph.D., Assistant Professor, Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England
Animal models have not sufficiently "filtered" targets for new analgesics. Evidence indicates that there are important mechanistic differences between evoked behavioral responses indicating hypersensitivity and ongoing pain, diminishing potential effectiveness of translation between preclinical measures of evoked hypersensitivity and pain "that is just there" within the clinic. New preclinical measures examining mechanisms underlying ongoing pain are currently being explored and may help in the process of filtering targets for the transition from drug discovery to drug development.
4:05 Refreshment Break in the Exhibit Hall with Poster Viewing
5:00 Plenary Keynote Presentation:
Catalyzing Translational Innovation
Christopher P. Austin, M.D., Director, National Center for Advancing, Translational Sciences, National Institutes of Health
6:00 Networking Reception in the Exhibit Hall with Poster Viewing
7:00 Close of Day
Day 1 | Day 2 | Pain Therapeutics Brochure | Speaker Biographies