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Nicotinic Receptors in Neurodegeneration
Send Orders of Reprints at [email protected] 298 Current Neuropharmacology, 2013, 11, 298-314 Nicotinic Receptors in Neurodegeneration Inmaculada Posadas, Beatriz López-Hernández and Valentín Ceña* Unidad Asociada Neurodeath. CSIC-Universidad de Castilla-La Mancha, Departamento de Ciencias Médicas. Albacete, Spain and CIBERNED, Instituto de Salud Carlos III, Spain Abstract: Many studies have focused on expanding our knowledge of the structure and diversity of peripheral and central nicotinic receptors. Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop superfamily of pentameric ligand-gated ion channels, which include GABA (A and C), serotonin, and glycine receptors. Currently, 9 alpha (2-10) and 3 beta (2-4) subunits have been identified in the central nervous system (CNS), and these subunits assemble to form a variety of functional nAChRs. The pentameric combination of several alpha and beta subunits leads to a great number of nicotinic receptors that vary in their properties, including their sensitivity to nicotine, permeability to calcium and propensity to desensitize. In the CNS, nAChRs play crucial roles in modulating presynaptic, postsynaptic, and extrasynaptic signaling, and have been found to be involved in a complex range of CNS disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, Tourette´s syndrome, anxiety, depression and epilepsy. Therefore, there is growing interest in the development of drugs that modulate nAChR functions with optimal benefits and minimal adverse effects. The present review describes the main characteristics of nAChRs in the CNS and focuses on the various compounds that have been tested and are currently in phase I and phase II trials for the treatment of neurodegenerative diseases including PD, AD and age-associated memory and mild cognitive impairment. -
(19) United States (12) Patent Application Publication (10) Pub
US 20130289061A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0289061 A1 Bhide et al. (43) Pub. Date: Oct. 31, 2013 (54) METHODS AND COMPOSITIONS TO Publication Classi?cation PREVENT ADDICTION (51) Int. Cl. (71) Applicant: The General Hospital Corporation, A61K 31/485 (2006-01) Boston’ MA (Us) A61K 31/4458 (2006.01) (52) U.S. Cl. (72) Inventors: Pradeep G. Bhide; Peabody, MA (US); CPC """"" " A61K31/485 (201301); ‘4161223011? Jmm‘“ Zhu’ Ansm’ MA. (Us); USPC ......... .. 514/282; 514/317; 514/654; 514/618; Thomas J. Spencer; Carhsle; MA (US); 514/279 Joseph Biederman; Brookline; MA (Us) (57) ABSTRACT Disclosed herein is a method of reducing or preventing the development of aversion to a CNS stimulant in a subject (21) App1_ NO_; 13/924,815 comprising; administering a therapeutic amount of the neu rological stimulant and administering an antagonist of the kappa opioid receptor; to thereby reduce or prevent the devel - . opment of aversion to the CNS stimulant in the subject. Also (22) Flled' Jun‘ 24’ 2013 disclosed is a method of reducing or preventing the develop ment of addiction to a CNS stimulant in a subj ect; comprising; _ _ administering the CNS stimulant and administering a mu Related U‘s‘ Apphcatlon Data opioid receptor antagonist to thereby reduce or prevent the (63) Continuation of application NO 13/389,959, ?led on development of addiction to the CNS stimulant in the subject. Apt 27’ 2012’ ?led as application NO_ PCT/US2010/ Also disclosed are pharmaceutical compositions comprising 045486 on Aug' 13 2010' a central nervous system stimulant and an opioid receptor ’ antagonist. -
Joel L. Young, M.D
Joel L. Young, M.D. 441 South Livernois Road, Suite 100 Rochester Hills, Michigan 48307 Phone: 248-608-8800 / Fax: 248-608-2490 / E-mail: [email protected] Professional History 2000 – Present: Chief Medical Officer and Founder, Clinical Trials Group at the Rochester Center for Behavioral Medicine, Rochester Hills, MI 1993 – Present: Medical Director and Founder, Rochester Center for Behavioral Medicine, Rochester Hills, MI (www.rcbm.net). 2008 (Current): Clinical Associate Professor of Psychiatry, Wayne State University, Detroit, MI. 2000 – 2007: Medical Director, Crittenton Network for Behavioral Health, Rochester, MI. 2000 – 2002: Chief of Staff, Department of Psychiatry, Crittenton Hospital, Rochester, MI. July, 1993 – 1997: Medical Director, Psychiatric Emergency Services, Crittenton Hospital. July, 1992 – June, 1993: Chief Resident of Adult Services, Department of Psychiatry, University of Michigan Hospitals, Ann Arbor, MI. Oct. 1991-Sept. 1993: Unit Psychiatrist, Bon Secours Adolescent Mental Health Unit, Grosse Pointe, MI. August, 1991 – 1996: Consulting Psychiatrist, Beacon Hill Clinic, Birmingham, MI. July, 1991 – June, 1992: Consulting Psychiatrist, Washtenaw County Community Mental Health Services, Ann Arbor, MI. July, 1990 – June, 1992: House Officer, Department of Psychiatry, University of Michigan Hospitals. June, 1989 – June, 1990: Intern, Departments of Internal Medicine, Pediatrics and Psychiatry, University of Michigan Hospitals. Boards 2018 Fellow: American Board of Psychiatry and Neurology 2017 Re-certification of Geriatric Qualifications by the American Board of Psychiatry and Neurology through 2027. 2017 Re-certification of Forensic Qualifications by the American Board of Psychiatry and Neurology through 2027 2014 Re-Certification by the American Board of Psychiatry and Neurology 2007 Re-certification by the American Board of Adolescent Psychiatry. -
Supported by an Educational Grant from Sunovion Pharmaceuticals Inc. Faculty
Supported by an educational grant from Sunovion Pharmaceuticals Inc. Faculty Leslie Citrome, MD, MPH C. Brendan Montano, MD Clinical Professor of Psychiatry and CT Clinical Research Behavioral Sciences Director, Principal Investigator New York Medical College Private Practice, Internal Medicine Valhalla, New York Cromwell, Connecticut Faculty Disclosure • Dr. Citrome: Consultant—Acadia, Alkermes, Allergan, Intra-Cellular Therapeutics, Janssen, Lundbeck, Merck, Neurocrine, Noven, Osmotica, Otsuka, Pfizer, Shire, Sunovion, Takeda, Teva, Vanda; Royalties—Springer Healthcare (book), UpToDate (reviewer), Wiley (Editor in Chief, International Journal of Clinical Practice); Shareholder (and spouse)—Bristol-Myers Squibb, Eli Lilly, J & J, Merck, Pfizer; Speaker—Acadia, Alkermes, Allergan, Janssen, Lundbeck, Merck, Neurocrine, Otsuka, Pfizer, Shire, Sunovion, Takeda, Teva. • Dr. Montano: Consultant—Allergan, Shire/Takeda Pharmaceutical Company Ltd., Sunovion Pharmaceuticals Inc., Arbor Pharmaceuticals Ltd.; Research Support—Allergan, Avanir, Sunovion Pharmaceuticals Inc., Tonix, BioHaven, Axsome Therapeutics, Arbor Pharmaceuticals Ltd.; Speakers Bureau— Allergan, Shire/Takeda Pharmaceutical Company Ltd., Arbor Pharmaceutical Ltd. Disclosure • The faculty have been informed of their responsibility to disclose to the audience if they will be discussing off-label or investigational use(s) of drugs, products, and/or devices (any use not approved by the US Food and Drug Administration). – The off-label and investigational use of antidepressants, topiramate, -
Horizon Scanning Status Report June 2019
Statement of Funding and Purpose This report incorporates data collected during implementation of the Patient-Centered Outcomes Research Institute (PCORI) Health Care Horizon Scanning System, operated by ECRI Institute under contract to PCORI, Washington, DC (Contract No. MSA-HORIZSCAN-ECRI-ENG- 2018.7.12). The findings and conclusions in this document are those of the authors, who are responsible for its content. No statement in this report should be construed as an official position of PCORI. An intervention that potentially meets inclusion criteria might not appear in this report simply because the horizon scanning system has not yet detected it or it does not yet meet inclusion criteria outlined in the PCORI Health Care Horizon Scanning System: Horizon Scanning Protocol and Operations Manual. Inclusion or absence of interventions in the horizon scanning reports will change over time as new information is collected; therefore, inclusion or absence should not be construed as either an endorsement or rejection of specific interventions. A representative from PCORI served as a contracting officer’s technical representative and provided input during the implementation of the horizon scanning system. PCORI does not directly participate in horizon scanning or assessing leads or topics and did not provide opinions regarding potential impact of interventions. Financial Disclosure Statement None of the individuals compiling this information have any affiliations or financial involvement that conflicts with the material presented in this report. Public Domain Notice This document is in the public domain and may be used and reprinted without special permission. Citation of the source is appreciated. All statements, findings, and conclusions in this publication are solely those of the authors and do not necessarily represent the views of the Patient-Centered Outcomes Research Institute (PCORI) or its Board of Governors. -
Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011
CLASSIFICATION DECISIONS TAKEN BY THE HARMONIZED SYSTEM COMMITTEE FROM THE 47TH TO 60TH SESSIONS (2011 - 2018) WORLD CUSTOMS ORGANIZATION Rue du Marché 30 B-1210 Brussels Belgium November 2011 Copyright © 2011 World Customs Organization. All rights reserved. Requests and inquiries concerning translation, reproduction and adaptation rights should be addressed to [email protected]. D/2011/0448/25 The following list contains the classification decisions (other than those subject to a reservation) taken by the Harmonized System Committee ( 47th Session – March 2011) on specific products, together with their related Harmonized System code numbers and, in certain cases, the classification rationale. Advice Parties seeking to import or export merchandise covered by a decision are advised to verify the implementation of the decision by the importing or exporting country, as the case may be. HS codes Classification No Product description Classification considered rationale 1. Preparation, in the form of a powder, consisting of 92 % sugar, 6 % 2106.90 GRIs 1 and 6 black currant powder, anticaking agent, citric acid and black currant flavouring, put up for retail sale in 32-gram sachets, intended to be consumed as a beverage after mixing with hot water. 2. Vanutide cridificar (INN List 100). 3002.20 3. Certain INN products. Chapters 28, 29 (See “INN List 101” at the end of this publication.) and 30 4. Certain INN products. Chapters 13, 29 (See “INN List 102” at the end of this publication.) and 30 5. Certain INN products. Chapters 28, 29, (See “INN List 103” at the end of this publication.) 30, 35 and 39 6. Re-classification of INN products. -
WO 2016/001643 Al 7 January 2016 (07.01.2016) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/001643 Al 7 January 2016 (07.01.2016) P O P C T (51) International Patent Classification: (74) Agents: GILL JENNINGS & EVERY LLP et al; The A61P 25/28 (2006.01) A61K 31/194 (2006.01) Broadgate Tower, 20 Primrose Street, London EC2A 2ES A61P 25/16 (2006.01) A61K 31/205 (2006.01) (GB). A23L 1/30 (2006.01) (81) Designated States (unless otherwise indicated, for every (21) International Application Number: kind of national protection available): AE, AG, AL, AM, PCT/GB20 15/05 1898 AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (22) International Filing Date: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, 29 June 2015 (29.06.2015) HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (25) Filing Language: English KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (26) Publication Language: English PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (30) Priority Data: SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 141 1570.3 30 June 2014 (30.06.2014) GB TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 1412414.3 11 July 2014 ( 11.07.2014) GB (84) Designated States (unless otherwise indicated, for every (71) Applicant: MITOCHONDRIAL SUBSTRATE INVEN¬ kind of regional protection available): ARIPO (BW, GH, TION LIMITED [GB/GB]; 39 Glasslyn Road, London GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, N8 8RJ (GB). -
Treatment-Resistant Attention-Deficit Hyperactivity Disorder: Clinical
Review Treatment-resistant Attention-deficit Hyperactivity Disorder: Clinical Significance, Concept, and Management Mu‑Hong Chen, M.D., Ph.D.1,2, Kai‑Lin Huang, M.D.1,2, Ju‑Wei Hsu, M.D.1,2,*, Shih‑Jen Tsai, M.D.1,2,* 1Department of Psychiatry, Taipei Veterans General Hospital, 2Division of Psychiatry, School of Medicine, National Yang‑Ming University, Taipei, Taiwan Abstract Background: Attention-deficit hyperactivity disorder (ADHD) is the most commonly diagnosed neurodevelopmental disorder known to cause impairment across the lifespan. ADHD was ranked as approximately the 50th leading cause of global years lived with disability for children, coming in ahead of diabetes, meningitis, and intellectual disability. About 20%–40% of patients with ADHD would not achieve the treatment response and symptomatic remission, increasing future risks of substance abuse, suicidal behavior, and premature mortality. However, there is no standard consensus for defining treatment resistance in ADHD.Method: In this systematic review, we intend to focus on treatment-resistant ADHD in the aspects of disease definition, psychopathology, pathophysiology, and treatment. Results: We suggest that the more ideal strategy of defining treatment resistance should consider the improvement of ADHD symptoms and the global functioning simultaneously. Psychiatric comorbidities (i.e. destructive behavior disorders and mood disorders), physical comorbidities (i.e. epilepsy), and psychosocial adversities (i.e. parental psychopathology and poor family functioning) should be the first to be assessed in the evaluation of treatment response or resistance. The optimal medication adjustment or the combination of medications and psychotherapy may be the potential therapeutic strategy for treatment-resistant ADHD. Conclusion: Further studies would be necessary to elucidate the underlying mechanisms of treatment-resistant ADHD and to research the novel treatment strategies for ADHD. -
Rxoutlook® 1St Quarter 2019
® RxOutlook 1st Quarter 2020 optum.com/optumrx a RxOutlook 1st Quarter 2020 Orphan drugs continue to feature prominently in the drug development pipeline In 1983 the Orphan Drug Act was signed into law. Thirty seven years later, what was initially envisioned as a minor category of drugs has become a major part of the drug development pipeline. The Orphan Drug Act was passed by the United States Congress in 1983 in order to spur drug development for rare conditions with high unmet need. The legislation provided financial incentives to manufacturers if they could demonstrate that the target population for their drug consisted of fewer than 200,000 persons in the United States, or that there was no reasonable expectation that commercial sales would be sufficient to recoup the developmental costs associated with the drug. These “Orphan Drug” approvals have become increasingly common over the last two decades. In 2000, two of the 27 (7%) new drugs approved by the FDA had Orphan Designation, whereas in 2019, 20 of the 48 new drugs (42%) approved by the FDA had Orphan Designation. Since the passage of the Orphan Drug Act, 37 years ago, additional regulations and FDA designations have been implemented in an attempt to further expedite drug development for certain serious and life threatening conditions. Drugs with a Fast Track designation can use Phase 2 clinical trials to support FDA approval. Drugs with Breakthrough Therapy designation can use alternative clinical trial designs instead of the traditional randomized, double-blind, placebo-controlled trial. Additionally, drugs may be approved via the Accelerated Approval pathway using surrogate endpoints in clinical trials rather than clinical outcomes. -
ADHD Investor Event Presentation
ADHD Investor Event October 11, 2018 Cautionary Note Regarding Presentation Information This presentation contains forward-looking statements, including statements about our plans to develop and commercialize our product candidates, our planned clinical trials for our prodrug product candidates, the timing of and our ability to obtain and maintain regulatory approvals for our product candidates, including expectations about our ability to use the 505(b)(2) pathway and expedited FDA review, the clinical utility of our product candidates and our intellectual property position. These statements involve substantial known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. The forward-looking statements in this presentation represent our views as of the date of this presentation. These and other risks concerning our business are described in additional detail in our Quarterly Report on Form 10-Q filed with the SEC on August 10, 2018, and our other Periodic and Current Reports filed with the SEC. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we have no current intention of doing so except to the extent required by applicable law. -
Drug Delivery System for Use in the Treatment Or Diagnosis of Neurological Disorders
(19) TZZ __T (11) EP 2 774 991 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 10.09.2014 Bulletin 2014/37 C12N 15/86 (2006.01) A61K 48/00 (2006.01) (21) Application number: 13001491.3 (22) Date of filing: 22.03.2013 (84) Designated Contracting States: • Manninga, Heiko AL AT BE BG CH CY CZ DE DK EE ES FI FR GB 37073 Göttingen (DE) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO •Götzke,Armin PL PT RO RS SE SI SK SM TR 97070 Würzburg (DE) Designated Extension States: • Glassmann, Alexander BA ME 50999 Köln (DE) (30) Priority: 06.03.2013 PCT/EP2013/000656 (74) Representative: von Renesse, Dorothea et al König-Szynka-Tilmann-von Renesse (71) Applicant: Life Science Inkubator Betriebs GmbH Patentanwälte Partnerschaft mbB & Co. KG Postfach 11 09 46 53175 Bonn (DE) 40509 Düsseldorf (DE) (72) Inventors: • Demina, Victoria 53175 Bonn (DE) (54) Drug delivery system for use in the treatment or diagnosis of neurological disorders (57) The invention relates to VLP derived from poly- ment or diagnosis of a neurological disease, in particular oma virus loaded with a drug (cargo) as a drug delivery multiple sclerosis, Parkinsons’s disease or Alzheimer’s system for transporting said drug into the CNS for treat- disease. EP 2 774 991 A1 Printed by Jouve, 75001 PARIS (FR) EP 2 774 991 A1 Description FIELD OF THE INVENTION 5 [0001] The invention relates to the use of virus like particles (VLP) of the type of human polyoma virus for use as drug delivery system for the treatment or diagnosis of neurological disorders. -
Activities of Nicotinic Acetylcholine Receptors Modulate Neurotransmission and Synaptic Architecture
NEURAL REGENERATION RESEARCH December 2014,Volume 9,Issue 24 www.nrronline.org INVITED REVIEW Activities of nicotinic acetylcholine receptors modulate neurotransmission and synaptic architecture Akira Oda1, Hidekazu Tanaka2 1 CNS Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 2-26-1, Muraoka-higashi, Fujisawa, Kanagawa 251-8555, Japan 2 Laboratory of Pharmacology, Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, 1-1-1, Noji-higashi, Kusatsu, Shiga 525-8577, Japan Abstract Corresponding author: The cholinergic system is involved in a broad spectrum of brain function, and its failure has Hidekazu Tanaka, M.D., Ph.D., been implicated in Alzheimer’s disease. Acetylcholine transduces signals through muscarinic Laboratory of Pharmacology, Department and nicotinic acetylcholine receptors, both of which influence synaptic plasticity and cognition. of Biomedical Sciences, College of Life However, the mechanisms that relate the rapid gating of nicotinic acetylcholine receptors to per- Sciences, Ritsumeikan University, sistent changes in brain function have remained elusive. Recent evidence indicates that nicotinic [email protected]. acetylcholine receptors activities affect synaptic morphology and density, which result in per- sistent rearrangements of neural connectivity. Further investigations of the relationships between doi:10.4103/1673-5374.147943 nicotinic acetylcholine receptors and rearrangements of neural circuitry in the central nervous http://www.nrronline.org/ system may help understand the pathogenesis of Alzheimer’s disease. Accepted: 2014-11-03 Key Words: cholinergic system; nicotinic acetylcholine receptors (nAChRs); Alzheimer’s disease (AD); synaptic transmission; synaptic plasticity; synaptic morphology; dendritic spine remodeling; cognition Funding: Tanaka H is supported by the Takeda Science Foundation and JSPS KAKENHI Grant Number 19590247.