DOCSLIB.ORG

13Th Clinical Trials on Alzheimer's Disease (CTAD) November 4-7, 2020

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
13Th Clinical Trials on Alzheimer's Disease (CTAD) November 4-7, 2020 JPAD is now indexed in SciSearch and Current Contents TheJ JournalP of PreventionA of AlzheimerD’s Disease 13th Clinical Trials on Alzheimer’s Disease (CTAD) November 4-7, 2020 Content of CTAD abstracts cannot be publicly shared until the date/time the session is available on demand or presented live. • Epidemiology • Biomarkers • Intervention • Clinical Trials J PA D The Journal of Prevention of Alzheimer’s Disease www.springer.com/medicine/neurology/journal/42414 S1 Volume 7, Supplement 1, 2020 Volume JPAD VOLUME 7, SUPPLEMENT 1, 2020 The Journal of Prevention of Alzheimer’s Disease© www.jpreventionalzheimer.com Impact factor: 3.149 (2019) The Journal of Prevention of Alzheimer’s Disease is indexed and abstracted in Science Citation Index Expanded (SciSearch), Journal Citation Reports/Science Edition, EMBASE, Google Scholar, Current Contents/Clinical Medicine, EBSCO Discovery Service, OCLC WorldCat Discovery Service, ProQuest-ExLibris Primo, ProQuest-ExLibris Summon and listed in Medline/PubMed. Editor-in-Chief: JPAD The Journal of Prevention of Alzheimer’s Disease© is Jacques Touchon (Montpellier, France) Bruno Vellas (Toulouse, France) published four times per year by Serdi Edition Paul Aisen (San Diego, USA) - Address for manuscript submission: Sections and Associate Editor www.editorialmanager.com/jpad • Methodological Aspects of Preventive Trials: - Address for subscription, information: S. Andrieu (Toulouse, France) www.springer.com/journal/42414 • Operational Aspects of Preventive Trials: B. Vellas (Toulouse, France) - Advertising inquiries should be sent to Carine Giry, Assistant • Health Economic and Finances Aspects: Publisher, • e-mail: [email protected] A. Khachaturian (Washington, USA) Serdi cannot be held responsible for errors or for any consequences arising from the use of • Health Policy, Regulations: Z. Khachaturian (Potomac, USA) the information contained in this journal. The appearance of advertising in this journal does not constitute an endorsement or approval by Serdi of the quality or value of the product • Bioinformatics Analytics: advertised or of the claims made for it by its manufacturer. R. Thomas (San Diego, USA) Permission to photocopy articles: This publication is protected by copyright. Permission to • Intervention Pharmacological: photocopy must be secured in writing from Serdi. P. Aisen (San Diego, USA) Copyright by © Serdi and Springer Nature Switzerland AG 2019. All rights reserved. Printed • Non Pharmacological: in France. E. Larson (Seattle, USA) subscriptions • Health Promotion: M. Kivipelto (Stockholm, Sweden) 2020 ORDER FORM (4 issues/year) • Ethics : J. Karlawish (Philadelphia, USA) www.springer.com/journal/42414 • Imaging and Biomarkers: All countries (VAT excluded) M. Weiner (San Francisco, USA) Individual Institutional • Pre-Clinical Study N. Vita (Toulouse, France) By mail + on line 344€ / $377 925€ / $974 • Diabetes and Cognitive Decline: A. Sinclair (Bedfordshire, United Kingdom) Check, money order, purchase order enclosed. o Master card o Visa Exp. Date : ....................... Editorial Board Members Security code (last 3 number on the back side of the card) ..... K.J. Anstey (Canberra, Australia) V. Legrand (Sèvres, France) R. Bateman (Saint Louis, USA) J.A. Luchsinger (New York, USA) Name : ............................................. D. Bennett (Chicago, USA) M. Morris (Chicago, USA) Name on credit card : ................................. H.R. Brashear (San Francisco, USA) D. Peng (Beijing, China) C. Brayne (Cambridge, UK) R. Petersen (Rochester, USA) Title : ...................... ...................... J. Breitner (Montréal, Canada) E. Reiman (Phoenix, USA) Company/Institution ........... M. Carrillo (Chicago, USA) E. Richard (Amsterdam, The Netherland) J.M. Cedarbaum (Woodbridge, USA) C. Ritchie (London, UK) . P. Chan (Beijing, China) S. Salloway (Providence, USA) J. Cummings (Las Vegas, USA) C. Scerri (Msida, Malta) Street address : ............... R.S. Doody (Houston, USA) P. Scheltens (Amsterdam, The Netherlands) . B. Dubois (Paris, France) R. Schindler (New York, USA) H. Feldman (Vancouver, Canada) F.A. Schmitt (Lexington, USA) City : . State/Prov. .............. L. Feng (Singapore) E. Siemers (Indianapolis, USA) H. Fillit (New York, USA) D. Smith (Oxford, UK) Zip :. Country : ............... G. Frisoni (Brescia, Italy) R. Sperling (Boston, USA) Phone : ..................... Fax : ................... J. George (Luxembourg) P. Tariot (Phoenix, USA) M. Grundman (San Diego, USA) C. van Dyck (New Haven, USA) Signature ................... D. Gustafson (New York, USA) S. Villeneuve (Montréal, Canada) H.J. Hampel (Paris, France) P. Wang (Beijing, China) M. Isaac (London, United Kingdom) P. Whitehouse (Shaker Heights, USA) F. Jessen (Bonn, Germany) K. Yaffe (San Francisco, USA) T. Kwok (Shalin, Hong Kong) J.-T. Yu (Qingdao, China) Y. Lee (Suwon, Republic of Korea) Instruction for Authors available at the journal website (www.editorialmanager.com/jpad) ISSN 2274-5807 This journal is printed on acid-free paper JPAD The Journal of Prevention of Alzheimer’s Disease© - Volume 7, Supplement 1, 2020 The Journal of Prevention of Alzheimer’s Disease - JPAD Volume 7, Supplement 1, 2020 Contents The Journal of Prevention of Alzheimer’s Disease JPAD Volume 7, Supplement 1, 2020 Supplement: 13th Conference Clinical Trials Alzheimer’s Disease, November 4-7, 2020 S2 • Symposia - Oral Communications - Late Breaking News S55 • Posters S1 The Journal of Prevention of Alzheimer’s Disease - JPAD © Serdi and Springer Nature Switzerland AG 2020 Volume 7, Supplement 1, 2020 studies in small mammals, baboons, and macaques showed SYMPOSIA that UB-311 generated antibody responses, cleared insoluble amyloid and reduced amyloid toxicity. A Ph1 safety, S1- DEVELOPMENT OF A VACCINE FOR PREVENTION tolerability, and immunogenicity trial demonstrated that UB-311 AND TREATMENT OF ALZHEIMER’S DISEASE. S. 1 2 3 4 was safe, well-tolerated, and produced a specific antibody Hendrix , C. Jeffrey , R. Eric , M. Richard ((1) Pentara - Millcreek, response in all participants tested. A Ph2 trial included 45 USA; (2) Cns Innovations - Las Vegas; USA; (3) Banner Alzheimer’s patients at four sites; participants had a 97% immunologic Institute - Phoenix, USA; (4) Global Alzheimer’s Platform Foundation response rate. All secondary endpoints - including Amyloid - Washington Dc, USA) PET burden, CDR-SB, ADCS-ADL, ADAS-Cog and MMSE - Presentation 1: Past and current vaccine and immunotherapy pointed directionally in favor of UB-311. The most common development in Alzheimer’s disease adverse events were injection site-related reactions and asymptomatic ARIA-H. UB-311 is being advanced to Ph3 Developing vaccines for the treatment of Alzheimer’s disease in a randomized, double-blind, placebo-controlled study to poses unique challenges. Success for a vaccine approach aimed assess the efficacy, safety, and tolerability in participants with at endogenous targets relies on the ability to break immune mild AD dementia or MCI due to AD. Eligible participants tolerance and generate a humoral antibody response against will be 60-85 years old, have MMSE of 20-26, CDR global the desired epitopes. AN1792 was created using a synthetic scores of 0.5 or 1, and International Shopping List Test scores full-length Aβ1-42 peptide. Nineteen percent of patients in 1 standard deviation below the mean or greater, and positive the trial generated anti-Aβ antibody responses and showed amyloid imaging. The primary outcome measure is the CDR- improved memory and decreased levels of tau protein in the SB difference in change from baseline in the active treatment CSF. Postmortem pathology examination of former AN1792 groups vs placebo at week 73. Secondary outcomes include patients showed that the vaccine had markedly cleared ADAS-Cog 13 item, Amsterdam Instrumental Activities of Daily plaques from the brain. Vaccine candidates such as CAD106 Living Questionnaire, AD Composite Score (ADCOMS), MMSE, and UB-311 use selective epitopes and were developed to and safety and tolerability of UB 311. Biomarker outcomes avoid the undesirable inflammatory effects that were seen include NfL, p-tau, tau, amyloid PET, CSF (subgroup) and with AN1792. Studies of recent and current amyloid targeting plasma Aβ40 and Aβ42, and hippocampal and whole brain immunotherapies (18 therapeutics) and vaccine therapeutics volume as measured by MRI. The relationship between the (8) illustrate lessons learned regarding patient selection, clinical primary and biomarker outcomes will be assessed. and biomarker outcomes, dosing regimens and assessment of antibody response. A meta-analysis of 13 RCT of amyloid- Presentation 3: The promise of blood-based biomarkers in the based immunotherapies in AD showed statistically significant evaluation, approval and affordability in Alzheimer’s prevention improvement in ADAS-cog (p<0.01) on drug. Solanezumab therapies and AN1792 showed the largest effect sizes and safest profiles, but the rates of ARIA-E were significantly higher with Blood-based biomarkers (BBBs) have the potential to monoclonal antibodies. Positive ADAS-cog effect sizes were transform Alzheimer’s research, treatment and care. I will seen for AN1792, Solanezumab EXPEDITION 3, BAN2401 and note several promising BBB’s, suggest how they could Aducanumab ENGAGE. Earlier EXPEDITION studies also inform treatment development, accelerate the evaluation included moderate disease, with substantially lower effect sizes. and approval of vaccines and other prevention therapies,
Load more

Recommended publications
  • Parkinson Disease-Associated Cognitive Impairment
    PRIMER Parkinson disease-associated cognitive impairment Dag Aarsland 1,2 ✉ , Lucia Batzu 3, Glenda M. Halliday 4, Gert J. Geurtsen 5, Clive Ballard 6, K. Ray Chaudhuri 3 and Daniel Weintraub7,8 Abstract | Parkinson disease (PD) is the second most common neurodegenerative disorder, affecting >1% of the population ≥65 years of age and with a prevalence set to double by 2030. In addition to the defining motor symptoms of PD, multiple non-motor symptoms occur; among them, cognitive impairment is common and can potentially occur at any disease stage. Cognitive decline is usually slow and insidious, but rapid in some cases. Recently, the focus has been on the early cognitive changes, where executive and visuospatial impairments are typical and can be accompanied by memory impairment, increasing the risk for early progression to dementia. Other risk factors for early progression to dementia include visual hallucinations, older age and biomarker changes such as cortical atrophy, as well as Alzheimer-type changes on functional imaging and in cerebrospinal fluid, and slowing and frequency variation on EEG. However, the mechanisms underlying cognitive decline in PD remain largely unclear. Cortical involvement of Lewy body and Alzheimer-type pathologies are key features, but multiple mechanisms are likely involved. Cholinesterase inhibition is the only high-level evidence-based treatment available, but other pharmacological and non-pharmacological strategies are being tested. Challenges include the identification of disease-modifying therapies as well as finding biomarkers to better predict cognitive decline and identify patients at high risk for early and rapid cognitive impairment. Parkinson disease (PD) is the most common movement The full spectrum of cognitive impairment occurs in disorder and the second most common neurodegenera­ individuals with PD, from subjective cognitive decline tive disorder after Alzheimer disease (AD).
    [Show full text]
  • Shexiang Baoxin Pill, a Traditional Chinese Herbal Formula, Rescues the Cognitive Impairments in APP/ PS1 Transgenic Mice
    ORIGINAL RESEARCH published: 14 July 2020 doi: 10.3389/fphar.2020.01045 Shexiang Baoxin Pill, a Traditional Chinese Herbal Formula, Rescues the Cognitive Impairments in APP/ PS1 Transgenic Mice † † Wei-Hui Hu 1,2,3 , Shing-Hung Mak 1,2 , Zhong-Yu Zheng 1,2, Ying-Jie Xia 1,2, Miranda Li Xu 1,2, Ran Duan 1,2,3, Tina Ting-Xia Dong 1,2,3, Shao-Ping Li 4, Chang-Sen Zhan 5,6, Xiao-Hui Shang 5,6 and Karl Wah-Keung Tsim 1,2,3* 1 Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Shenzhen, China, 2 Division of Life Science and Center for Chinese Medicine and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, Hong Kong, 3 Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, China, 4 Institute of Chinese Medical Sciences, University of Macau, Macau, Macau, 5 Shanghai Edited by: Engineering Research Center for Innovation of Solid Preparation of TCM, Shanghai, China, 6 Shanghai Hutchison Qiaobing Huang, Pharmaceuticals Ltd., Shanghai, China Southern Medical University, China Reviewed by: Background: Shexiang Baoxin Pill (SBP), a formulated traditional Chinese medicine Bing-Xing Pan, Nanchang University, China (TCM), has been widely used to treat cardiovascular diseases for years. This herbal Wenda Xue, mixture has been shown to promote differentiation of cultured neuronal cells. Here, we Nanjing University of Chinese aimed to investigate the effects of SBP in attenuating cognitive impairment in APP/PS1 Medicine, China *Correspondence: transgenic mice.
    [Show full text]
  • The “Rights” of Precision Drug Development for Alzheimer's Disease
    Cummings et al. Alzheimer's Research & Therapy (2019) 11:76 https://doi.org/10.1186/s13195-019-0529-5 REVIEW Open Access The “rights” of precision drug development for Alzheimer’s disease Jeffrey Cummings1*, Howard H. Feldman2 and Philip Scheltens3 Abstract There is a high rate of failure in Alzheimer’s disease (AD) drug development with 99% of trials showing no drug- placebo difference. This low rate of success delays new treatments for patients and discourages investment in AD drug development. Studies across drug development programs in multiple disorders have identified important strategies for decreasing the risk and increasing the likelihood of success in drug development programs. These experiences provide guidance for the optimization of AD drug development. The “rights” of AD drug development include the right target, right drug, right biomarker, right participant, and right trial. The right target identifies the appropriate biologic process for an AD therapeutic intervention. The right drug must have well-understood pharmacokinetic and pharmacodynamic features, ability to penetrate the blood-brain barrier, efficacy demonstrated in animals, maximum tolerated dose established in phase I, and acceptable toxicity. The right biomarkers include participant selection biomarkers, target engagement biomarkers, biomarkers supportive of disease modification, and biomarkers for side effect monitoring. The right participant hinges on the identification of the phase of AD (preclinical, prodromal, dementia). Severity of disease and drug mechanism both have a role in defining the right participant. The right trial is a well-conducted trial with appropriate clinical and biomarker outcomes collected over an appropriate period of time, powered to detect a clinically meaningful drug-placebo difference, and anticipating variability introduced by globalization.
    [Show full text]
  • Criteria for the Diagnosis of Corticobasal Degeneration
    VIEWS & REVIEWS Criteria for the diagnosis of corticobasal degeneration Melissa J. Armstrong, ABSTRACT MD Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) Irene Litvan, MD no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An Anthony E. Lang, MD international consortium of behavioral neurology, neuropsychology, and movement disorders special- Thomas H. Bak, MD ists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses Kailash P. Bhatia, MD (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from pub- Barbara Borroni, MD lished reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal Adam L. Boxer, MD, syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary PhD progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features Dennis W. Dickson, MD of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing Murray Grossman, MD a comprehensive description of CBD and correcting common misconceptions. Clinical CBD pheno- Mark Hallett, MD types and features were combined to create 2 sets of criteria: more specific clinical research criteria Keith A. Josephs, MD for probable CBD and broader criteria for possibleCBDthataremoreinclusivebuthaveahigher Andrew Kertesz, MD chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and grad- Suzee E. Lee, MD ual progression for at least 1 year, age at onset $50 years, no similar family history or known tau Bruce L. Miller, MD mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS Stephen G.
    [Show full text]
  • OREXIN ANTAGONISTS BELSOMRA (Suvorexant), DAYVIGO (Lemborexant)
    OREXIN ANTAGONISTS BELSOMRA (suvorexant), DAYVIGO (lemborexant) RATIONALE FOR INCLUSION IN PA PROGRAM Background Belsomra (suvorexant) and Dayvigo (lemborexant) are orexin receptor antagonists used to treat difficulty in falling and staying asleep (insomnia). Orexins are chemicals that are involved in regulating the sleep-wake cycle and play a role in keeping people awake (1-2). Regulatory Status FDA-approved indication: Orexin receptor antagonists are indicated for the treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance (1-2). Orexin Antagonists are contraindicated in patients with narcolepsy (1-2). Orexin Antagonists are central nervous system (CNS) depressants that can impair daytime wakefulness even when used as prescribed. Medications that treat insomnia can cause next-day drowsiness and impair driving and other activities that require alertness. Orexin Antagonists can impair driving skills and may increase the risk of falling asleep while driving. People can be impaired even when they feel fully awake. Patients should also be made aware of the potential for next-day driving impairment, because there is individual variation in sensitivity to the drug (1-2). The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or mental illness that should be evaluated (1-2). Warnings and precautions that should be discussed with the patient on Orexin Antagonist therapy include adverse reactions on abnormal thinking and behavioral changes (such as amnesia, anxiety, hallucinations and other neuropsychiatric symptoms), complex behaviors (such as sleep- driving, preparing and eating food, or making phone calls), dose-dependent increase in suicidal ideation, and sleep paralysis which is the inability to move or speak for up to several minutes during sleep-wake transitions (1-2).
    [Show full text]
  • Current Research Efforts in the Prevention and Treatment of Alzheimer’S Disease (AD) and Related Dementias
    Current Research efforts in the prevention and treatment of Alzheimer’s Disease (AD) and Related Dementias What’s new? 1. New and More effective Biomarkers 2. New Diagnostic Framework : • New “A/T/N” Framework • New Framework conceptualizes AD as a continuum from pathophysiological, biomarker and clinical perspectives. 3. LATE (Limbic-predominant, Age-related, TDP-43 Encephalopathy) looks like Alzheimer’s disease 4. Alzheimer’s pathophysiology starts decades prior to clinical disease! 1. New and More Effective Biomarkers AD Pathology • Alzheimer’s Disease consists of two main features: • Senile plaques (β-amyloid)- earliest pathological event! • Neurofibrillary tangles (hyperphosphorylated tau)- primary culprit in cells death • Mechanism: • β-amyloid hyperphosphorylated tau tau spreads throughout the brain from neuron to neuron (Pooler et al, 2013). Cell Death Biomarkers Budson & Solomon, Practical Neurology 2012;12:88–96 PET Amyloid Imaging was approved since 2012 • Use when knowing that AD pathology is present in symptomatic patient would change management. • May detect amyloid plaques in asymptomatic patients who may not develop disease for 10-15+ years • Not paid for by Medicare or other insurance companies • Can obtain through Veterans Affairs hospitals, clinical trials/research studies, and self-pay. • Will have broader use when disease modifying therapies are available. Alzheimer’s Disease Non-AD dementia 65 year old MoCA 21 From Budson & Solomon, 2016 PET tau imaging : FDA approved May 2020 • Use when knowing that AD pathology is present in symptomatic patient would change management. • Will detect AD tau tangles in symptomatic patients and should correlate with symptoms • May detect other types of tau tangles in other dementias (not yet clear) • Not paid for by Medicare or other insurance companies • Can obtain through Veterans Affairs hospitals, clinical trials/research studies, and self-pay.
    [Show full text]
  • Perspective Rxpipeline a Pharmacy
    A PHARMACY ON PERSPECTIVE THE RXPIPELINE Understanding changes in the medication market and their impact on cost and care. EnvisionPharmacies continuously monitors the drug pipeline. As treatment options change, we evaluate and share our perspective on the clinical benefits, cost-effectiveness and overall impact to payers, physicians and patients. Our Perspective on the Rx Pipeline report provides insights on what you should expect from your pharmacy partners to get patients the treatment they need. Included in this Edition } Clinical Pipeline } FDA Drug Approvals } New Indications } Upcoming and Recent Generic Launches } FDA Safety Update } Drug Shortages and Discontinuations 1 | A PHARMACY PERSPECTIVE ON THE RXPIPELINE • OCTOBER 2019 Clinical Pipeline PIPELINE STAGE R & D FDA In Market Off Patent Open Source Off Approved Brand Exclusive Generic Alternative Market crizanlizumab SEG101 Manufacturer: Novartis Indication/Use: Sickle cell disease Dosage Form: Infusion Pipeline Stage: PDUFA 1/2020 Sickle cell disease is a debilitating genetic blood disorder that affects approximately 100,000 Americans.[1] Patients with sickle cell disease can suffer from vaso-occlusive crises (VOCs) that are incredibly painful and can cause irreversible tissue infarction and vasculopathy. VOCs are also associated with increased morbidity and mortality. [2] Hydroxyurea and pharmacy-grade L-glutamine are the only two FDA-approved pharmacotherapies currently available for the prevention of VOCs.[3] Crizanlizumab is a monoclonal antibody that works through selectin
    [Show full text]
  • Drug Candidates in Clinical Trials for Alzheimer's Disease
    Hung and Fu Journal of Biomedical Science (2017) 24:47 DOI 10.1186/s12929-017-0355-7 REVIEW Open Access Drug candidates in clinical trials for Alzheimer’s disease Shih-Ya Hung1,2 and Wen-Mei Fu3* Abstract Alzheimer’s disease (AD) is a major form of senile dementia, characterized by progressive memory and neuronal loss combined with cognitive impairment. AD is the most common neurodegenerative disease worldwide, affecting one-fifth of those aged over 85 years. Recent therapeutic approaches have been strongly influenced by five neuropathological hallmarks of AD: acetylcholine deficiency, glutamate excitotoxicity, extracellular deposition of amyloid-β (Aβ plague), formation of intraneuronal neurofibrillary tangles (NTFs), and neuroinflammation. The lowered concentrations of acetylcholine (ACh) in AD result in a progressive and significant loss of cognitive and behavioral function. Current AD medications, memantine and acetylcholinesterase inhibitors (AChEIs) alleviate some of these symptoms by enhancing cholinergic signaling, but they are not curative. Since 2003, no new drugs have been approved for the treatment of AD. This article focuses on the current research in clinical trials targeting the neuropathological findings of AD including acetylcholine response, glutamate transmission, Aβ clearance, tau protein deposits, and neuroinflammation. These investigations include acetylcholinesterase inhibitors, agonists and antagonists of neurotransmitter receptors, β-secretase (BACE) or γ-secretase inhibitors, vaccines or antibodies targeting Aβ clearance or tau protein, as well as anti-inflammation compounds. Ongoing Phase III clinical trials via passive immunotherapy against Aβ peptides (crenezumab, gantenerumab, and aducanumab) seem to be promising. Using small molecules blocking 5-HT6 serotonin receptor (intepirdine), inhibiting BACE activity (E2609, AZD3293, and verubecestat), or reducing tau aggregation (TRx0237) are also currently in Phase III clinical trials.
    [Show full text]
  • [14C]Lemborexant in Healthy Human Subjects and Characterization of Its Circulating Metabolites
    DMD Fast Forward. Published on November 3, 2020 as DOI: 10.1124/dmd.120.000229 This article has not been copyedited and formatted. The final version may differ from this version. Title Page Title: Disposition and Metabolism of [14C]Lemborexant in Healthy Human Subjects and Characterization of Its Circulating Metabolites Authors: Downloaded from Takashi Ueno, Tomomi Ishida, Jagadeesh Aluri, Michiyuki Suzuki, Carsten T. Beuckmann, Takaaki Kameyama, Shoji Asakura, Kazutomi Kusano dmd.aspetjournals.org Affiliation: Eisai Co., Ltd., Ibaraki, Japan (T.U., T.I., C.B., T.K., S.A., K.K.) Eisai Inc., Woodcliff Lake, NJ, U.S. (J.A.) EA Pharma Co., Ltd., Tokyo, Japan (M.S.) at ASPET Journals on September 24, 2021 1 DMD Fast Forward. Published on November 3, 2020 as DOI: 10.1124/dmd.120.000229 This article has not been copyedited and formatted. The final version may differ from this version. Running Title Page Running title: ADME properties of lemborexant in humans Corresponding Author: Takashi Ueno Downloaded from Drug Metabolism and Pharmacokinetics, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan. Phone: +81-29-847-5658 dmd.aspetjournals.org FAX: +81-29-847-5672 E-mail: [email protected] Number of text pages: 35 at ASPET Journals on September 24, 2021 Number of tables: 5 Number of figures: 3 Number of references: 23 Number of words in the Abstract: 249 Number of words in the Introduction: 665 Number of words in the Discussion: 1241 2 DMD Fast Forward. Published on November 3, 2020 as DOI: 10.1124/dmd.120.000229 This article has not been copyedited and formatted.
    [Show full text]
  • (RVX-208) in Ex Vivo Treated Human Whole Blood and Primary Hepatocytes
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Data in Brief 8 (2016) 1280–1288 Contents lists available at ScienceDirect Data in Brief journal homepage: www.elsevier.com/locate/dib Data Article Data on gene and protein expression changes induced by apabetalone (RVX-208) in ex vivo treated human whole blood and primary hepatocytes Sylwia Wasiak a, Dean Gilham a, Laura M. Tsujikawa a, Christopher Halliday a, Karen Norek a, Reena G. Patel a, Kevin G. McLure a, Peter R. Young b, Allan Gordon b, Ewelina Kulikowski a, Jan Johansson b, Michael Sweeney b, Norman C. Wong a,n a Resverlogix Corp., Calgary, Canada b Resverlogix Corp., San Francisco, USA article info abstract Article history: Apabetalone (RVX-208) inhibits the interaction between epige- Received 28 January 2016 netic regulators known as bromodomain and extraterminal (BET) Received in revised form proteins and acetyl-lysine marks on histone tails. Data presented 5 July 2016 here supports the manuscript published in Atherosclerosis “RVX- Accepted 22 July 2016 208, a BET-inhibitor for Treating Atherosclerotic Cardiovascular Dis- Available online 29 July 2016 ease, Raises ApoA-I/HDL and Represses Pathways that Contribute to Keywords: Cardiovascular Disease” (Gilham et al., 2016) [1]. It shows that RVX- Bromodomain 208 and a comparator BET inhibitor (BETi) JQ1 increase mRNA BET proteins expression and production of apolipoprotein A-I (ApoA-I), the BET inhibitor main protein component of high density lipoproteins, in primary RVX-208 JQ1 human and African green monkey hepatocytes. In addition, Vascular inflammation reported here are gene expression changes from a microarray- ApoA-I based analysis of human whole blood and of primary human Apolipoprotein A-I hepatocytes treated with RVX-208.
    [Show full text]
  • Corticobasal Syndrome: Clinical, Neuropsychological, Imaging
    CORTICOBASAL SYNDROME: CLINICAL, NEUROPSYCHOLOGICAL, IMAGING, GENETIC AND PATHOLOGICAL FEATURES by Mario Masellis A thesis submitted in conformity with the requirements for the degree of Doctorate of Philosophy in the Graduate Department of Institute of Medical Sciences, University of Toronto © Copyright by Mario Masellis (2012) Library and Archives Bibliothèque et Canada Archives Canada Published Heritage Direction du Branch Patrimoine de l'édition 395 Wellington Street 395, rue Wellington Ottawa ON K1A 0N4 Ottawa ON K1A 0N4 Canada Canada Your file Votre référence ISBN: 978-0-494-97827-6 Our file Notre référence ISBN: 978-0-494-97827-6 NOTICE: AVIS: The author has granted a non- L'auteur a accordé une licence non exclusive exclusive license allowing Library and permettant à la Bibliothèque et Archives Archives Canada to reproduce, Canada de reproduire, publier, archiver, publish, archive, preserve, conserve, sauvegarder, conserver, transmettre au public communicate to the public by par télécommunication ou par l'Internet, prêter, telecommunication or on the Internet, distribuer et vendre des thèses partout dans le loan, distrbute and sell theses monde, à des fins commerciales ou autres, sur worldwide, for commercial or non- support microforme, papier, électronique et/ou commercial purposes, in microform, autres formats. paper, electronic and/or any other formats. The author retains copyright L'auteur conserve la propriété du droit d'auteur ownership and moral rights in this et des droits moraux qui protege cette thèse. Ni thesis. Neither the thesis nor la thèse ni des extraits substantiels de celle-ci substantial extracts from it may be ne doivent être imprimés ou autrement printed or otherwise reproduced reproduits sans son autorisation.
    [Show full text]
  • What Every Social Worker Physical Therapist Occupational
    What Every Social Worker Physical Therapist Occupational Therapist Speech-Language Pathologist Should Know About Progressive Supranuclear Palsy (PSP) Corticobasal Degeneration (CBD) Multiple System Atrophy (MSA) A Comprehensive Guide to Signs, Symptoms, and Management Strategies DISEASE SUMMARIES at a glance Progressive Supranuclear Palsy (PSP) • Rare neurodegenerative disease, the most common parkinsonian disorder after Parkinson’s disease (PD) • Originally described in 1964 as Steele-Richardson-Olszewski syndrome • Often mistakenly diagnosed as PD due to the similar early symptoms • Symptoms include early postural instability, supranuclear gaze palsy (paralysis of voluntary vertical gaze with preserved reflexive eye movements), and levodopa-nonresponsive parkinsonism • Onset of symptoms is typically symmetric • Pathologically classified as a tauopathy (abnormal accumulation in the brain of the protein tau) • Five to seven cases per 100,000 people • Slightly more common in men • Average age of onset is 60–65 years, but can occur as early as age 40 • Life expectancy is five to seven years following symptom onset • No cure or effective medication management Signs and Symptoms • Early onset gait and balance problems • Clumsy, slow, or shuffling gait 2 • Lack of coordination • Slowed or absent balance reactions and postural instability • Frequent falls (primarily backward) • Slowed movements • Rigidity (generally axial) • Vertical gaze palsy • Loss of downward gaze is usually first • Abnormal eyelid control • Decreased blinking with “staring”
    [Show full text]