Current Landscape of Treatments for Wolfram Syndrome
Publication date: Available online 13 August 2019Source: Trends in Pharmacological SciencesAuthor(s): Damien Abreu, Fumihiko UranoWolfram syndrome is a rare genetic spectrum disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration, and ranges from mild to severe clinical symptoms. There is currently no treatment to delay, halt, or reverse the progression of Wolfram syndrome, raising the urgency for innovative therapeutics for this disease. Here, we summarize our vision for developing novel treatment strategies and achieving a cure for Wolfram-syndrome-spectrum di...
Source: Trends in Pharmacological Sciences - August 13, 2019 Category: Drugs & Pharmacology Source Type: research
Neuro-regeneration Therapeutic for Alzheimer’s Dementia: Perspectives on Neurotrophic Activity
Publication date: Available online 8 August 2019Source: Trends in Pharmacological SciencesAuthor(s): Miao-Kun Sun, Daniel L. AlkonAlzheimer’s disease (AD), the leading disorder of memory impairment in our aging population, is increasing at an alarming rate. AD is currently identified by three ‘gold standard criteria’: (i) dementia in life, (ii) amyloid plaques at autopsy, and (iii) neurofibrillary tangles at autopsy. Several autopsy studies have indicated that dementia in life is a consequence of lost synaptic networks in the brain, while many clinical trials targeting neurotoxic amyloid beta (Aβ) have consistently ...
Source: Trends in Pharmacological Sciences - August 9, 2019 Category: Drugs & Pharmacology Source Type: research
Cell-Specific Neuropharmacology
Publication date: Available online 7 August 2019Source: Trends in Pharmacological SciencesAuthor(s): Sarah Mondoloni, Romain Durand-de Cuttoli, Alexandre MourotNeuronal communication involves a multitude of neurotransmitters and an outstanding diversity of receptors and ion channels. Linking the activity of cell surface receptors and ion channels in defined neural circuits to brain states and behaviors has been a key challenge in neuroscience, since cell targeting is not possible with traditional neuropharmacology. We review here recent technologies that enable the effect of drugs to be restricted to specific cell types, t...
Source: Trends in Pharmacological Sciences - August 8, 2019 Category: Drugs & Pharmacology Source Type: research
Targeting TRP Channels – Valuable Alternatives to Combat Pain, Lower Urinary Tract Disorders, and Type 2 Diabetes?
Publication date: Available online 5 August 2019Source: Trends in Pharmacological SciencesAuthor(s): Thomas Voets, Joris Vriens, Rudi VennekensTransient receptor potential (TRP) channels are a family of functionally diverse and widely expressed cation channels involved in a variety of cell signaling and sensory pathways. Research in the last two decades has not only shed light on the physiological roles of the 28 mammalian TRP channels, but also revealed the involvement of specific TRP channels in a plethora of inherited and acquired human diseases. Considering the historical successes of other types of ion channels as the...
Source: Trends in Pharmacological Sciences - August 6, 2019 Category: Drugs & Pharmacology Source Type: research
The Molecular Function of σ Receptors: Past, Present, and Future
Publication date: Available online 3 August 2019Source: Trends in Pharmacological SciencesAuthor(s): Hayden R. Schmidt, Andrew C. KruseThe σ1 and σ2 receptors are enigmatic proteins that have attracted attention for decades due to the chemical diversity and therapeutic potential of their ligands. However, despite ongoing clinical trials with σ receptor ligands for multiple conditions, relatively little is known regarding the molecular function of these receptors. In this review, we revisit past research on σ receptors and discuss the interpretation of these data in light of recent developments. We provide a synthesis o...
Source: Trends in Pharmacological Sciences - August 4, 2019 Category: Drugs & Pharmacology Source Type: research
Substrate-Selective Enzyme Inhibitors
Publication date: Available online 2 August 2019Source: Trends in Pharmacological SciencesAuthor(s): Qian Chu, Tina Chang, Alan SaghatelianEnzymes with multiple substrates pose a unique challenge for drug development because of an increased potential for on-target side effects. Maianti and colleagues (Nat. Chem. Biol., 2019) identify novel exo-site inhibitors with abilities to alter the substrate-selectivity of insulin-degrading enzymes (IDE). Their work illuminates new therapeutic avenues for discovering small-molecule enzyme inhibitors and redefines our current understanding of drugging enzymes with multiple substrates. ...
Source: Trends in Pharmacological Sciences - August 3, 2019 Category: Drugs & Pharmacology Source Type: research
Artificial Intelligence for Drug Toxicity and Safety
Publication date: Available online 2 August 2019Source: Trends in Pharmacological SciencesAuthor(s): Anna O. Basile, Alexandre Yahi, Nicholas P. TatonettiInterventional pharmacology is one of medicine’s most potent weapons against disease. These drugs, however, can result in damaging side effects and must be closely monitored. Pharmacovigilance is the field of science that monitors, detects, and prevents adverse drug reactions (ADRs). Safety efforts begin during the development process, using in vivo and in vitro studies, continue through clinical trials, and extend to postmarketing surveillance of ADRs in real-world pop...
Source: Trends in Pharmacological Sciences - August 3, 2019 Category: Drugs & Pharmacology Source Type: research
Small Molecules to Improve ER Proteostasis in Disease
Publication date: Available online 31 July 2019Source: Trends in Pharmacological SciencesAuthor(s): Vicente Gonzalez-Teuber, Hector Albert-Gasco, Vincent C. Auyeung, Feroz R. Papa, Giovanna R. Mallucci, Claudio HetzAbnormally high levels of misfolded proteins in the endoplasmic reticulum (ER) lumen result in a stress state that contributes to the progression of several pathological conditions including diabetes, cancer, neurodegeneration, and immune dysregulation. ER stress triggers a dynamic signaling pathway known as the unfolded protein response (UPR). The UPR enforces adaptive or cell death programs by integrating info...
Source: Trends in Pharmacological Sciences - August 1, 2019 Category: Drugs & Pharmacology Source Type: research
Potential of Epigenetic Therapy for Prader-Willi Syndrome
Publication date: Available online 25 July 2019Source: Trends in Pharmacological SciencesAuthor(s): Sung Eun Wang, Yong-hui JiangPrader-Willi syndrome (PWS) is a neurobehavioral and epigenetic disorder caused by the deficiency of paternally expressed genes in the chromosome 15q11-q13. This unique molecular defect renders PWS an exciting opportunity to explore epigenetic therapy. Here, we briefly highlight recent findings from small molecule screening and CRISPR/Cas9-mediated epigenome editing that offer promising therapeutic options along with the challenges that remain in developing a successful epigenetic therapy for PWS...
Source: Trends in Pharmacological Sciences - July 26, 2019 Category: Drugs & Pharmacology Source Type: research
Editorial Board and Contents
Publication date: August 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 8Author(s): (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - July 25, 2019 Category: Drugs & Pharmacology Source Type: research
Subscription and Copyright Information
Publication date: August 2019Source: Trends in Pharmacological Sciences, Volume 40, Issue 8Author(s): (Source: Trends in Pharmacological Sciences)
Source: Trends in Pharmacological Sciences - July 25, 2019 Category: Drugs & Pharmacology Source Type: research
Tumor Vasculatures: A New Target for Cancer Immunotherapy
Publication date: Available online 20 July 2019Source: Trends in Pharmacological SciencesAuthor(s): Zhigang Liu, Yifan Wang, Yuhui Huang, Betty Y.S. Kim, Hong Shan, Depei Wu, Wen JiangImmune cells rely on a functional vascular network to enter tissues. In solid tumors, blood vessels are abnormal and dysfunctional and, thus, immune effector cell infiltration is impaired. Although normalizing the tumor vasculature has been shown to improve the efficacy of cancer immunotherapies, recent studies suggest that enhanced immune stimulation also, in turn, improves tumor vascular normalization. Thus, this new paradigm of immune syst...
Source: Trends in Pharmacological Sciences - July 20, 2019 Category: Drugs & Pharmacology Source Type: research
Artificial Intelligence for Clinical Trial Design
Publication date: Available online 17 July 2019Source: Trends in Pharmacological SciencesAuthor(s): Stefan Harrer, Pratik Shah, Bhavna Antony, Jianying HuClinical trials consume the latter half of the 10 to 15 year, 1.5–2.0 billion USD, development cycle for bringing a single new drug to market. Hence, a failed trial sinks not only the investment into the trial itself but also the preclinical development costs, rendering the loss per failed clinical trial at 800 million to 1.4 billion USD. Suboptimal patient cohort selection and recruiting techniques, paired with the inability to monitor patients effectively during trial...
Source: Trends in Pharmacological Sciences - July 18, 2019 Category: Drugs & Pharmacology Source Type: research
Insights into Computational Drug Repurposing for Neurodegenerative Disease
Publication date: Available online 17 July 2019Source: Trends in Pharmacological SciencesAuthor(s): Manish D. Paranjpe, Alice Taubes, Marina SirotaComputational drug repurposing has the ability to remarkably reduce drug development time and cost in an era where these factors are prohibitively high. Several examples of successful repurposed drugs exist in fields such as oncology, diabetes, leprosy, inflammatory bowel disease, among others, however computational drug repurposing in neurodegenerative disease has presented several unique challenges stemming from the lack of validation methods and difficulty in studying heterog...
Source: Trends in Pharmacological Sciences - July 18, 2019 Category: Drugs & Pharmacology Source Type: research
Advancing Drug Discovery via Artificial Intelligence
Publication date: Available online 15 July 2019Source: Trends in Pharmacological SciencesAuthor(s): H.C. Stephen Chan, Hanbin Shan, Thamani Dahoun, Horst Vogel, Shuguang YuanDrug discovery and development are among the most important translational science activities that contribute to human health and wellbeing. However, the development of a new drug is a very complex, expensive, and long process which typically costs 2.6 billion USD and takes 12 years on average. How to decrease the costs and speed up new drug discovery has become a challenging and urgent question in industry. Artificial intelligence (AI) combined with ne...
Source: Trends in Pharmacological Sciences - July 17, 2019 Category: Drugs & Pharmacology Source Type: research
