Author Interviews, Diabetes, NEJM / 09.02.2023

MedicalResearch.com Interview with: Brian S Kim, MD, MTR Sol and Clara Kest Professor Vice Chair of Research | Site Chair, Mount Sinai West and Morningside Director, Mark Lebwohl Center for Neuroinflammation and Sensation The Kimberly and Eric J. Waldman Department of Dermatology Precision Immunology Institute | Friedman Brain Institute Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Response: We generated preliminary data in mice that difelikefalin suppresses itch robustly with very little to no effect on inflammation in a model of atopic dermatitis. This led us to hypothesize that the primary mode of action of difelikefalin must be by direct modulation of sensory neurons to suppress itch and thus would be best suited for a neuropathic itch condition. These are conditions in which itch occurs relatively independently of skin inflammation as in atopic dermatitis due to hyperactive nerves. (more…)
Author Interviews, Dermatology, PNAS / 01.06.2021

MedicalResearch.com Interview with: Haley Steele Graduate Student Researcher Georgia Institute of Technology  MedicalResearch.com: What is the background for this study? Response: Chronic itch is a debilitating symptom that arises from a broad range of etiologies including skin disease, systemic disease, and as a common side-effect of medication. While in the last few decades significant advances in our understanding of the mechanisms underlying chronic itch have been made, a large majority of those advancements were restricted to studies in hairy skin. Conditions such as plantar and palmar psoriasis, dyshidrosis, and cholestasis, however, are known to exhibit chronic itch restricted primarily to glabrous skin (found on the palms of hands and soles of feet). This is an area that is considered to be particularly debilitating. Therefore, in this study we investigated the role three previously identified pruriceptive neurons (MrgprA3+, MrgprD+, and MrgprC11+) play in mediating acute and chronic glabrous skin itch. (more…)
Author Interviews, Dermatology / 05.04.2021

MedicalResearch.com Interview with: Wolfgang Liedtke, M.D., Ph.D. Professor (tenured) of Neurology, Anesthesiology and Neurobiology
Attending Physician, Duke Neurology Clinics for Headache, Head-Pain and Trigeminal Sensory Disorders
Attending Physician, Duke Clinics for Innovative Pain Therapy at Brier Creek (Dept of Anesthesiology)
Duke University School of Medicine, Center for Translational Neuroscience
Durham NC 27710 Since April 2021 Chair of Neurology Global Development Scientific Council Regeneron Pharmaceuticals Tarrytown NY 10591 MedicalResearch.com: What is the background for this study? Response: There are systemic diseases that are characterized by intense itching, yet without inflammation of the skin and not associated with allergic inflammation. For example and importantly, liver disease with non-functional secretion of bile (cholestatic liver disease, most common primary biliary cholangitis, an autoimmune disease), but also chronic end-stage renal disease (also certain lymphomas and pruritic psoriasis where the itch is whole-body, not only restricted to diseased skin). We thought that these diseases might be great starting points to better understand itch because there is no inflamed skin and no allergies. Thus, there must be some systemic factor that causes itch, and we were intent on discovering such factors, and with them, molecular mechanisms how they cause itch. For cholestatic liver disease, one of the best candidates to fit this profile has been lysophosphatidic acid (LPA), since the pioneering discoveries of Andreas Kremer, one of our co-authors. My research laboratory at Duke has been rooted in my discovery of TRPV4 ion channels 20 years ago, out of the Friedman Lab at The Rockefeller University in NYC. Over the years, with my colleague Yong Chen out of my lab, now leading his own independent research operation, we focused on the role of TRPV4 ion channels in skin. 5 years ago Yong and I published a paper that provided some evidence for TRPV4 in skin perhaps playing a role in itch. Working with phospholipids, we made the serendipitous discovery that lysophosphatidyl choline (LPC) is a more potent itch-inducing lipid molecule than LPA. Of note, LPC is the metabolic precursor of LPA. We then found that LPA does not depend on TRPV4 to elicit itch. The more robust itch evoked by LPC was significantly reduced when we knocked down TRPV4 in skin keratinocytes. Itch was NOT affected when TRPV4 was deleted from sensory nerve cells that innervate the skin. In terms of background, my long-term goal has been to elucidate how innervating peripheral nerve cell and innervated organ, such as skin, talk to one another so that the sensation that is felt is regulated or modulated, e.g how can skin influence itch or pain, how can joint cells influence pain. That became the exciting bedrock of our study, and we took it from there, 5 years of hard work with collaborations spanning the globe, and a final stretch of exhausting work during the pandemic. (more…)
Author Interviews, Dermatology / 15.01.2021

MedicalResearch.com Interview with: Brian Kim, MD Associate Professor of Dermatology Co-Director, Center for the Study of Itch & Sensory Disorders John T. Milliken Department of Internal Medicine Washington University in St. Louis MedicalResearch.com: What is the background for this study? Response: Patients with eczema suffer from chronic itch due to the rashes they have on their body. However, as a physician, I have always noticed that patients with eczema will have sudden flares of their itching all over there body that is often triggered by what appear to be allergens – being around a cat, pollen, mold in a house, etc. Eczema is in the family of allergic diseases such as food allergy, asthma, and hay fever. All of these conditions are noted for patients being reactive to allergens by way of an antibody called IgE that coats a cell called the mast cell. Upon IgE binding an allergen, mast cells produce tons of histamine which can cause symptoms like itching. So we speculated that perhaps because patients with eczema have such misbehaving IgE, that exposure to allergen is what triggers this kind of severe itch flare that we see in patients. (more…)
Author Interviews, Dermatology, Kidney Disease / 22.06.2020

MedicalResearch.com Interview with: Gil Yosipovitch, MD, Professor Miami Itch Center Lennar Medical Foundation South Miami Clinic in Coral Gables University of Miami Health System MedicalResearch.com: What is the background for this study? Response: Chronic Pruritus is a common and burdensome condition in patients with end stage chronic kidney disease (CKD). It is Present at all stages of CKD, not only in patients undergoing hemodialysis (including stage 3-5 CKD). There are no approved treatments for this condition in US and Europe. CKD pruritus   has significant impact on quality of life of patients with higher mortality rates due to its effect on sleep. Studies in the last 2 decades have shown that in patients with CKD pruritus there is an imbalance between endogenous mu opioids that are over expressed to Kappa Opioids that are down regulated.   Difelikefalin (DFK) is a novel peripherally selective kappa opioid receptor (KOR) agonist.   Study of IV DFK administration  in hemodialysis patients has  recently  been published and showed significant anti Pruritic effect ( NEJM Fishbane et al. 382: 289-290, 2020). (more…)
Author Interviews, Dermatology / 13.05.2020

MedicalResearch.com Interview with: Brian S. Kim, MD, MTR, FAAD Associate Professor of Medicine (Dermatology) Co-Director, Center for the Study of Itch and Sensory Disorders Division of Dermatology, Department of Medicine Washington University School of Medicine St. Louis, MO  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Itch is the central and most debilitating symptom of atopic dermatitis. However, surprisingly, measuring itch or quality of life in clinical trials is not often a primary endpoint. Therefore, this study focuses in very detailed fashion on how ruxolitinib cream improves pruritus in a clinically meaningful way and its ultimate impact on quality of life. What patients want to know at the end of the day is how much will this drug change my life?  Not, whether it statistically beat out a placebo group. Indeed, what this study shows is that ruxolitinib cream has a major impact on itch in a meaningful way that is also tied to improvements in quality of life. (more…)
Author Interviews, Dermatology, Neurology / 28.04.2020

MedicalResearch.com Interview with: Santosh K. Mishra M.Tech., PhD Assistant Professor of Neuroscience Department of Molecular Biomedical Sciences NC State Veterinary Medicine Raleigh, NC 2760 MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by atopic dermatitis? Response: Chronic allergic itch is a worldwide problem that leads to substantial health expenses,but what causes this universal urge to scratch remains elusive in chronic allergic itch. Atopic dermatitis is a common allergic skin disease that often associated with extremely itchy and inflamed skin. In our study, we showed, for the first time, a molecular pathway that is involved in chronic allergic itch as we identified an endogenous mediator (periostin) and a new role for its sensory neuron receptor, the integrin αVβ3, which drives the excitability and transmission of itch signal to the spinal cord.  (more…)
Allergies, Author Interviews, Dermatology / 20.03.2020

MedicalResearch.com Interview with: Gil Yosipovitch, MD, Professor Miami Itch Center Lennar Medical Foundation South Miami Clinic in Coral Gables University of Miami Health System MedicalResearch.com: What is the background for this study? How does Dupilumab (Dupixent) differ from other medications for atopic dermatitis/eczema? Response: Atopic dermatitis (AD) is characterized by intense itch (pruritus) that is one of the most burdensome symptoms; therefore, rapid and sustained improvement in itch is an important marker of treatment benefit. Dupixent® (dupilumab) is approved in the U.S. for adults and adolescents with inadequately-controlled moderate-to-severe Atopic Dermatitis. Dupilumab remains the first and only biologic medicine for uncontrolled moderate-to-severe atopic dermatitis. Dupilumab is the first and only fully human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) proteins. Data from dupilumab clinical trials have shown that IL-4 and IL-13 are key drivers of the type 2 inflammation that plays a major role in atopic dermatitis, asthma and chronic rhinosinusitis with nasal polyps.  (more…)
Author Interviews, Dermatology, Johns Hopkins / 15.06.2018

MedicalResearch.com Interview with: Dr. Shawn Kwatra MD Assistant Professor of Dermatology Johns Hopkins University School of Medicine  MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by prurigo nodularis?  Response: Prurigo nodularis is a skin condition where patients develop extremely itchy nodules throughout the body. Little is known about why this happens or which groups of people are predisposed to develop this condition. MedicalResearch.com: What are the main findings? Response We found that prurigo nodularis disproportionately affects African-Americans as compared to the general population. Diabetes, Hepatitis C, chronic kidney disease, and HIV are also more common in patients with prurigo nodularis than the general population or patients with other inflammatory skin diseases studied, such as atopic dermatitis and psoriasis. We also found that people with prurigo nodularis are more likely to be depressed than patients with other inflammatory skin diseases, such as atopic dermatitis or psoriasis.  (more…)
Author Interviews, Dermatology, Hepatitis - Liver Disease, NEJM / 07.06.2018

MedicalResearch.com Interview with: Dr Christophe Corpechot Centre de Référence Maladie Rares: Maladies Inflammatoires des Voies Biliaires et Hépatites Auto-immunes (MIVB-H) Filière Maladies Rares: Maladies Rares du Foie de l’Adulte et de l’Enfant Hôpital Saint-Antoine (APHP) et Sorbonne Universités Paris MedicalResearch.com: What is the background for this study? Response: Primary biliary cholangitis (PBC, previously known as "primary biliary cirrhosis") is a rare, chronic, slowly progressive liver disease of unknown cause, mainly affecting women of middle age. It is characterized by serum marks of autoimmunity (specific auto-antibodies), chronic inflammation and destruction of small intra-hepatic bile ducts, and consequent bile secretion impairment (chronic cholestasis) leading to the progressive development of cirrhosis and liver failure. Ursodeoxycholic acid (UDCA) is the only first-line approved treatment for PBC. It improves the biochemical measures of cholestasis and prolongs survival without liver transplantation. However, 30% to 40% of UDCA-treated patients continue to have clinically significant abnormalities of their biochemical liver tests and those patients remain at high risk of developing end-stage liver disease complications. Recently (2016), obeticholic acid (OCA) in association with UDCA has been conditionally approved in patients with an inadequate response to UDCA. This approval (FDA, EMA) was based one the results of a 1-year randomized, double-blind, placebo-controlled trial of OCA in patients with an incomplete response or intolerance to UDCA (POISE trial). In this trial, OCA was shown to improve the biochemical features of cholestasis (alkaline phosphatase (ALP) level < 1.67 times the upper limit of the normal range and a reduction of at least 15% from baseline) but was associated with a significant increase of pruritus, a characteristic, potentially debilitating symptom of PBC. BEZURSO is the first ever placebo-controlled phase 3 trial of a fibrate (a class of drugs known to be agonists of the peroxisome proliferator-activated receptors alpha) in PBC. In this 2-year randomized double-blind trial, 100 patients with an incomplete response to UDCA were assigned to bezafibrate 400 mg/day (n=50) or placebo (n=50), all in association with continued UDCA therapy. (more…)
Author Interviews, Cannabis, Dermatology / 21.04.2017

MedicalResearch.com Interview with: Jessica S. Mounessa, BS University of Colorado School of Medicine Aurora, Colorado and Robert Dellavalle, MD, PhD, MSPH Professor of Dermatology and Public Health University of Colorado School of Medicine Colorado School of Public Health Chief, Dermatology Service US Department of Veterans Affairs Eastern Colorado Health Care System Denver, CO 80220  MedicalResearch.com: What is the background for this study? What are the main findings? Response: One in 10 adult cannabis users in the U.S. use it for medicinal purposes. Medicinal cannabis is well studied for its uses in chronic pain, anorexia, and nausea. Numerous recent studies have highlighted other medicinal uses for cannabinoids and related compounds. We conducted a comprehensive review of the literature on the potential role of cannabinoids in conditions affecting the skin. Our study reveals the potential benefit of topically prepared cannabinoid compounds, especially for pruritus and eczema.  For example, creams containing Palmitoylethanolamide (PEA), which enhances cannabinoid-receptor binding, have been successful in relieving itch both in the literature, and anecdotally in our clinics. Though not strictly considered an endocannabinoid, as it does not directly bind to CB1 and CB2 receptors, PEA works by enhancing endocannabinoid binding to these receptors.** Furthermore, the majority of the cannabinoid compounds we studied did not contain psychoactive effects. (more…)
Author Interviews, Dermatology, Johns Hopkins, Pain Research / 24.02.2017

MedicalResearch.com Interview with: Xinzhong Dong PhD The Solomon H. Snyder Department of Neuroscience and Center for Sensory Biology Howard Hughes Medical Institute Johns Hopkins University School of Medicine Baltimore, MD 21205 MedicalResearch.com: What is the background for this study? What are the main findings? Response: It is a puzzle that troubles the field for many years that how pain and itch, two closely related sensations (once thought as one sensation), are differentiated by the nervous systems. Coding of pain and itch are heatedly debated for decades. The current specificity theory suggests that these two kinds of signals are carried by separate pathways, with some interactions, for example pain can inhibit itch and that explains why we all scratch to inhibit pain. It is true in the periphery (our previous study indicate a small population of neurons in the periphery only codes for itch sensation), but now our study suggests that there could be more crosstalk between these two sensations in the central than we expected. People might not notice in real life, but in human psychophysical studies, well-isolated experimental environments, when human subjects are given itchy substances, they typically report intense itch sensations accompanied by minor noxious sensations, such as pricking, stinging and burning. Our new leaky gate model suggest in certain circumstances intense itch signals can trigger minor pain sensations, which can explain such phenomenon. (more…)
Author Interviews, Dermatology, Science / 20.07.2016

MedicalResearch.com Interview with: Dr. Devin M. Barry, PhD, postdoc fellow Center for the Study of Itch,. Department of Anesthesiology Washington University School of Medicine St. Louis, MO 63110 MedicalResearch.com: What is the background for this study? Response: Our group is interested in understanding the molecular and cellular mechanisms that underly itch sensation. Our study focused on peripheral sensory neurons of the DRG that mediate responses to itch-inducing stimuli, in particular the inflammatory mediator histamine and the antimalarial drug chloroquine. It has been shown that histamine and chloroquine activate distinct G protein–coupled receptors (GPCRs) in sensory neurons innervating the skin. Two members of the transient receptor potential (TRP) family of ion channels, TRPV1 and TRPA1, have been found to be important mediators of histamine- and chloroquine-induced itch signaling, respectively. (more…)
Author Interviews, Dermatology, Kidney Disease / 30.09.2014

MedicalResearch.com Interview wth: Mei-Ju Ko, MD, PhD Department of Dermatology, Taipei City Hospital Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. Medical Research: What are the main findings of the study? Dr. Ko: In this study, not only did we find that serum levels of interleukin (IL)-31 were significantly higher in hemodialysis patients with pruritus symptoms, but we also demonstrated a positive exposure-response relationship between IL-31 levels and visual analog scale (VAS) scores of pruritus intensity. We also noted an inverse correlation between the severity of pruritus and the dialysis dose assessed by Kt/V. (more…)
Author Interviews, Dermatology, Duke, Pain Research / 26.05.2014

MedicalResearch.com Interview with: Seok-Yong Lee, Ph.D. Assistant Professor of BiochemistrySeok-Yong Lee, Ph.D. Assistant Professor of Biochemistry and Ru-Rong Ji, Ph.D. Distinguished Professor of Duke University Professor of Anesthesiology and Neurobiology Chief of Pain ResearchRu-Rong Ji, Ph.D. Distinguished Professor  of Duke University Professor of Anesthesiology  and Neurobiology Chief of Pain Research Duke University Medical Center Durham, NC 27710 MedicalResearch: What are the main findings of the study?

 Answer: We have developed an antibody that can block the pain and itching sensations in mice simultaneously with high efficacy. We would like to point out that our discovery has the potential to be applied to human once the antibody is humanized. Given the high selectivity, general safety profile, and long half-lives of monoclonal antibodies, this method we developed to raise antibodies against therapeutic targets (e.g., ion channels) can have broad applications to other diseases. (more…)