DOCSLIB.ORG

Neurology Webcast Presentation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Neurology Webcast Presentation Neurology Webcast July 14, 2020 Forward Looking Language Statement This presentation includes forward-looking statements regarding our business, financial guidance and the therapeutic and commercial potential of SPINRAZA® (nusinersen) and Ionis' technologies and products in development, including Ionis’ neurology franchise. Any statement describing Ionis’ goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, including those related to the impact COVID-19 could have on our business, and including but not limited to those related to our commercial products and the medicines in our pipeline, and particularly those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis’ forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2019 and our most recent Form 10-Q quarterly filing, which are on file with the SEC. Copies of this and other documents are available at www.ionispharma.com. In this presentation, unless the context requires otherwise, “Ionis,” “Company,” “we,” “our,” and “us” refers to Ionis Pharmaceuticals and its subsidiaries. Ionis Pharmaceuticals™ is a trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics® is a registered trademark of Akcea Therapeutics, Inc. SPINRAZA® is a registered trademark of Biogen. 2 Today’s Presenters Brett Monia, Ph.D. C. Frank Bennett, Ph.D. Chief Executive Officer Chief Scientific Officer Ionis Pharmaceuticals Ionis Pharmaceuticals Frank Rigo, Ph.D. Holly Kordasiewicz, Ph.D. VP, Functional Genomics & VP, Neurology Research Drug Discovery Ionis Pharmaceuticals Ionis Pharmaceuticals 3 Today’s Agenda Welcome and Introductions Wade Walke Ionis – The Leader in RNA-targeted Drug Discovery and Development Brett Monia Ionis – The Leader in Targeting Neurological Diseases Frank Bennett Amyotrophic Lateral Sclerosis Frank Bennett & Frank Rigo Alzheimer’s Disease and Dementia Holly Kordasiewicz Parkinson’s Disease and Multiple System Atrophy Holly Kordasiewicz Spinocerebellar Ataxias Holly Kordasiewicz Ionis-owned Medicines – Prion, Lafora and Alexander’s Diseases Holly Kordasiewicz Conclusion Brett Monia Q&A All 4 Ionis – The Leader in RNA-targeted Drug Discovery and Development Brett Monia Where We Are Today Our leadership position in RNA-targeted therapeutics continues to grow as our technology advances We have a large, diverse, expanding, and mature pipeline that continues to perform exceptionally well The Ionis-owned pipeline is a key priority, will expand substantially, and investments are underway to enhance our commercial capabilities We have the financial strength to continue advancing our technology and deliver on our pipeline To become the innovation leader in biotech providing hope and Vision transformational benefit to millions of patients living with severe diseases 6 Ionis Delivering Medicines for Most Major Severe Diseases NEUROLOGICAL NEUROMUSCULAR CARDIOVASCULAR METABOLIC UltraPULMONARY-rare to Common Diseases CANCER HEMATOLOGICAL KIDNEY OPHTHALMOLOGY INFECTIOUS DISEASE 7 The Ionis Neurological Disease Pipeline Validated platform • Proof of mechanism • Proof of safety • Proof of efficacy • Commercial success A rapidly expanding premier pipeline tackling the most severe diseases Continued technology advancement • Greater efficacy • Less frequent dosing • Systemic applications (e.g. neuromuscular) 8 Ionis is Cracking the Code in Neurological Diseases SPINRAZA Alexander disease Myotonic dystrophy Spinal muscular atrophy ION373 ATTR amyloidosis Prion disease TEGSEDI for hATTR polyneuropathy Spinocerebellar ataxias ION716 AKCEA-TTR-LRx for all major forms Huntington’s disease Lafora disease Spinal and Bulbar muscle Tominersen (IONIS-HTTRx) ION283 atrophy Alzheimer’s disease Multiple System Atrophy Charcot-Marie-Tooth IONIS-MAPTRx ION464 Amyotrophic lateral sclerosis Angelman syndrome Tofersen (IONIS-SOD1 ), IONIS-C9 , Multiple sclerosis Rx Rx ION581 ION541 (Sporadic), ION363 (FUS) Parkinson’s disease Severe epilepsies Severe pain ION859 Multiple Programs And many more in Centronuclear myopathy Leukodystrophies IONIS-DNM2-2.5Rx research stage 9 Ionis is Cracking the Code in Neurological Diseases Ionis-owned Neurological Programs SPINRAZA Alexander disease Myotonic dystrophy Spinal muscular atrophy ION373 ATTR amyloidosis Prion disease TEGSEDI for hATTR polyneuropathy Spinocerebellar ataxias ION716 AKCEA-TTR-LRx for all major forms Huntington’s disease Lafora disease Spinal and Bulbar muscle Tominersen (IONIS-HTTRx) ION283 atrophy Alzheimer’s disease Multiple System Atrophy Charcot-Marie-Tooth IONIS-MAPTRx ION464 Amyotrophic lateral sclerosis Angelman syndrome Tofersen (IONIS-SOD1 ), IONIS-C9 , Multiple sclerosis Rx Rx ION581 ION541 (Sporadic), ION363 (FUS) Parkinson’s disease Severe epilepsies Severe pain ION859 Multiple Programs And many more in Centronuclear myopathy Leukodystrophies IONIS-DNM2-2.5Rx research stage 10 Ionis – The Leader in Targeting Neurological Diseases Frank Bennett Advancing and Expanding Ionis’ Neurology Pipeline Pre-clinical and Clinical Development Programs* 40 • Tominersen (HD) 35 • Tofersen (ALS) 30 • TTR-LRx (ATTR) • IONIS-MAPT (AD) 25 Rx • IONIS-C9Rx (ALS) 20 • ION859 (PD) • IONIS-DNM2-2.5Rx (Centronuclear 15 Myopathy) 10 • ION373 (AxD) • ION464 (MSA) Neurology Projects Neurology 5 • ION541 (ALS) 0 • ION363 (ALS) 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 * Drug Discovery Preclinical Phase 1/2 Phase 3 Marketed * Projected by year-end 2020 12 Many Neurodegenerative Diseases are Caused by Toxic Proteins Expressed in Different Brain Regions Frontotemporal dementia Cerebral atrophy Huntington’s disease Misfolded TAU Whole brain atrophy HTT protein aggregates Alzheimer’s disease Cerebral and hippocampal atrophy Aβ plaques, TAU tangles Alexander’s disease Loss of myelin predominantly in Parkinson’s disease frontal lobe Loss of dopamine neurons in Rosenthal fibers-GFAP deposits substantia nigra and cortical atrophy Lewy bodies: alpha-synuclein Lewy body disease Amyotrophic lateral sclerosis Cerebral atrophy Atrophy of motor neurons and muscles Lewy bodies: alpha-synuclein Sporadic: TDP43 inclusions SOD1 Patients: Misfolded SOD1 C9 Patients: Dipeptide repeats and RNA foci 13 Ionis’ Neurological Pipeline Targets All Major Brain Regions Tofersen SOD1-Amyotrophic Lateral Sclerosis Spinal muscular atrophy 14 Ionis’ Neurological Pipeline Targets All Major Brain Regions Tominersen IONIS-MAPT Huntington’s Disease Rx Alzheimer’s Disease and ION373 Tauopathies Alexander Disease ION716 ION859 Parkinson’s Disease Prion Disease ION283 Lafora Disease ION464 Parkinson’s Disease and synucleinopathies Tofersen SOD1-Amyotrophic Lateral Sclerosis IONIS-C9Rx C9-Amyotrophic Lateral Sclerosis Spinal muscular atrophy ION541 Sporadic-Amyotrophic Lateral Sclerosis Phase 3 ION363 Phase 1/2 FUS-Amyotrophic Lateral Sclerosis Preclinical 15 Antisense Targets All CNS Cell Types Total cortex RNA Neurons 1 5 0 1 5 0 • Wild type (normal) mice E D : 3 2 g 5 0 E D 5 0 : 2 0 6 g ED50 = 329 5 %µgC I : 2 6 - 4 0 g ED = 206 µg n 50 9 5 % C I : 1 1 5 - 3 6 9 g o n i o s i s • Intracerebroventricular (ICV) bolus injection s e 1 0 0 s r e 1 0 0 ) p r x ) p S x E S of Malat1 antisense drug at a single dose B E B P A P A N % N ( R % ( R 1 5 0 t 1 5 0 a • Analyzed at 2 weeks after the dose by cell t l a a l a M sorting with antibody and qPCR M 0 0 1 0 1 0 0 1 0 0 0 1 0 1 0 0 1 0 0 0 A m o u n t in j e c t e d ( g ) A m o u n t in j e c t e d ( g ) Oligodendrocytes Astrocytes Microglia 1 5 0 1 5 0 1 5 0 E D : 1 7 g E D : 7 1 g E D 5 0 : 3 4 g 5 0 5 0 ED = 349 5 % CµgI : 2 1 - 5 5 g ED = 179 5 %µgC I : 1 3 - 2 3 g ED = 719 5 % C I :µg 5 5 - 9 1 g n n 50 50 n 50 o o o i i i s s s s s s e e e 1 0 0 1 0 0 1 0 0 r r r ) ) p p ) p x x x S S S E E E B B B P P P A A A N N N % % % ( ( ( R R R 1 1 1 5 0 5 0 5 0 t t t a a a l l l a a a M M M 0 0 0 1 0 1 0 0 1 0 0 0 1 0 1 0 0 1 0 0 0 1 0 1 0 0 1 0 0 0 A m o u n t in j e c t e d ( g ) A m o u n t in j e c t e d ( g ) A m o u n t in j e c t e d ( g ) The ED50 is the dose that produces a 50% reduction in the target RNA 16 Ionis’ Neurological Pipeline Also Targets the Peripheral Nervous System and Muscle AKCEA-TTR-LRx All major forms of TTR amyloidosis Polyneuropathy caused by hereditary transthyretin-mediated amyloidosis IONIS-DNM2-2.5Rx Centronuclear myopathy 17 Ionis’ Neurological Disease Pipeline MEDICINES INDICATION PARTNER PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Tominersen (IONIS-HTTRx) Huntington’s disease Roche Tofersen (IONIS-SOD1Rx) ALS Biogen TTR-LRx TTR Amyloidosis Ionis IONIS-MAPTRx Alzheimer’s disease Biogen IONIS-C9Rx ALS Biogen ION859 Parkinson’s disease Biogen Centronuclear IONIS-DNM2-2.5 Dynacure Rx myopathy Multiple System ION464 Biogen Atrophy ION541 ALS Biogen
Load more

Recommended publications
  • Lafora Disease: Molecular Etiology Lafora Hastalığı: Moleküler Etiyoloji S
    Epilepsi 2018;24(1):1-7 DOI: 10.14744/epilepsi.2017.48278 REVIEW / DERLEME Lafora Disease: Molecular Etiology Lafora Hastalığı: Moleküler Etiyoloji S. Hande ÇAĞLAYAN1,2 1Department of Molecular Biology and Genetics, Boğaziçi University, İstanbul, Turkey S. Hande CAĞLAYAN, Ph.D. 2International Biomedicine and Genome Center, Dokuz Eylül University, İzmir, Turkey Summary Lafora Disease (LD) is a fatal neurodegenerative condition characterized by the accumulation of abnormal glycogen inclusions known as Lafora bodies (LBs). Patients with LD manifest myoclonus and tonic-clonic seizures, visual hallucinations, and progressive neurological deteri- oration beginning at the age of 8-18 years. Mutations in either EPM2A gene encoding protein phosphatase laforin or NHLRC1 gene encoding ubiquitin-ligase malin cause LD. Approximately, 200 distinct mutations accounting for the disease are listed in the Lafora progressive my- oclonus epilepsy mutation and polymorphism database. In this review, the genotype-phenotype correlations, the genetic diagnosis of LD, the downregulation of glycogen metabolism as the main cause of LD pathogenesis and the regulation of glycogen synthesis as a key target for the treatment of LD are discussed. Key words: EPM2A and NHLRC1 gene mutations; genotype-phenotype relationship; Lafora progressive myoclonus epilepsy; LD pathogenesis. Özet Lafora hastalığı (LD) Lafora cisimleri (LB) olarak bilinen anormal glikojen yapıların birikmesi ile karakterize olan ölümcül bir nörodejeneratif hastalıktır. Lafora hastalarında 8–18 yaş arası başlayan miyoklonik ve tonik-klonik nöbetler, halüsinasyonlar ve ilerleyen nörolojik bozulma görülür. Lafora hastalığı protein fosfataz laforini kodlayan EPM2A geni veya ubikitin ligaz malini kodlayan NHLRC1 geni mutasyonları ile orta- ya çıkar. Hastalığa sebep olan yaklaşık 200 farklı mutasyon “Lafora Progressive Myoclonus Epilepsy Mutation and Polymorphism Database” de listelenmiştir.
    [Show full text]
  • ILAE Classification and Definition of Epilepsy Syndromes with Onset in Childhood: Position Paper by the ILAE Task Force on Nosology and Definitions
    ILAE Classification and Definition of Epilepsy Syndromes with Onset in Childhood: Position Paper by the ILAE Task Force on Nosology and Definitions N Specchio1, EC Wirrell2*, IE Scheffer3, R Nabbout4, K Riney5, P Samia6, SM Zuberi7, JM Wilmshurst8, E Yozawitz9, R Pressler10, E Hirsch11, S Wiebe12, JH Cross13, P Tinuper14, S Auvin15 1. Rare and Complex Epilepsy Unit, Department of Neuroscience, Bambino Gesu’ Children’s Hospital, IRCCS, Member of European Reference Network EpiCARE, Rome, Italy 2. Divisions of Child and Adolescent Neurology and Epilepsy, Department of Neurology, Mayo Clinic, Rochester MN, USA. 3. University of Melbourne, Austin Health and Royal Children’s Hospital, Florey Institute, Murdoch Children’s Research Institute, Melbourne, Australia. 4. Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Necker–Enfants Malades Hospital, APHP, Member of European Reference Network EpiCARE, Institut Imagine, INSERM, UMR 1163, Université de Paris, Paris, France. 5. Neurosciences Unit, Queensland Children's Hospital, South Brisbane, Queensland, Australia. Faculty of Medicine, University of Queensland, Queensland, Australia. 6. Department of Paediatrics and Child Health, Aga Khan University, East Africa. 7. Paediatric Neurosciences Research Group, Royal Hospital for Children & Institute of Health & Wellbeing, University of Glasgow, Member of European Refence Network EpiCARE, Glasgow, UK. 8. Department of Paediatric Neurology, Red Cross War Memorial Children’s Hospital, Neuroscience Institute, University of Cape Town, South Africa. 9. Isabelle Rapin Division of Child Neurology of the Saul R Korey Department of Neurology, Montefiore Medical Center, Bronx, NY USA. 10. Programme of Developmental Neurosciences, UCL NIHR BRC Great Ormond Street Institute of Child Health, Department of Clinical Neurophysiology, Great Ormond Street Hospital for Children, London, UK 11.
    [Show full text]
  • Mutations in the NHLRC1 Gene Are the Common Cause for Lafora Disease in the Japanese Population
    J Hum Genet (2005) 50:347–352 DOI 10.1007/s10038-005-0263-7 ORIGINAL ARTICLE Shweta Singh Æ Toshimitsu Suzuki Æ Akira Uchiyama Satoko Kumada Æ Nobuko Moriyama Æ Shinichi Hirose Yukitoshi Takahashi Æ Hideo Sugie Æ Koichi Mizoguchi Yushi Inoue Æ Kazue Kimura Æ Yukio Sawaishi Kazuhiro Yamakawa Æ Subramaniam Ganesh Mutations in the NHLRC1 gene are the common cause for Lafora disease in the Japanese population Received: 11 March 2005 / Accepted: 30 May 2005 / Published online: 15 July 2005 Ó The Japan Society of Human Genetics and Springer-Verlag 2005 Abstract Lafora disease (LD) is a rare autosomal NHLRC1 and encoding a putative E3 ubiquitin ligase, recessive genetic disorder characterized by epilepsy, was recently identified on chromosome 6p22. The LD is myoclonus, and progressive neurological deterioration. relatively common in southern Europe, the Middle East, LD is caused by mutations in the EMP2A gene encoding and Southeast Asia. A few sporadic cases with typical a protein phosphatase. A second gene for LD, termed LD phenotype have been reported from Japan; however, our earlier study failed to find EPM2A mutations in four Japanese families with LD. We recruited four new fam- S. Singh Æ S. Ganesh Department of Biological Sciences and Bioengineering, ilies from Japan and searched for mutations in EPM2A. Indian Institute of Technology, All eight families were also screened for NHLRC1 Kanpur, India mutations. We found five independent families having T. Suzuki Æ K. Yamakawa (&) novel mutations in NHLRC1. Identified mutations in- Laboratory for Neurogenetics, clude five missense mutations (p.I153M, p.C160R, RIKEN Brain Science Institute, 2-1, Hirosawa, Wako, p.W219R, p.D245N, and p.R253K) and a deletion Saitama 351-0198, Japan mutation (c.897insA; p.S299fs13).
    [Show full text]
  • Lafora Disease Masquerading As Hepatic Dysfunction
    Thomas Jefferson University Jefferson Digital Commons Abington Jefferson Health Papers Abington Jefferson Health 8-24-2018 Lafora Disease Masquerading as Hepatic Dysfunction Faisal Inayat Allama Iqbal Medical College Waqas Ullah Abington Jefferson Health Hanan T. Lodhi University of Nebraska at Omaha Zarak H. Khan St. Mary Mercy Hospital Livonia Ghulam Ilyas SUNY Downstate Medical Center Follow this and additional works at: https://jdc.jefferson.edu/abingtonfp See next page for additional authors Part of the Gastroenterology Commons, and the Medical Genetics Commons Let us know how access to this document benefits ouy Recommended Citation Inayat, Faisal; Ullah, Waqas; Lodhi, Hanan T.; Khan, Zarak H.; Ilyas, Ghulam; Ali, Nouman Safdar; and Abdullah, Hafez Mohammad A., "Lafora Disease Masquerading as Hepatic Dysfunction" (2018). Abington Jefferson Health Papers. Paper 7. https://jdc.jefferson.edu/abingtonfp/7 This Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital Commons is a service of Thomas Jefferson University's Center for Teaching and Learning (CTL). The Commons is a showcase for Jefferson books and journals, peer-reviewed scholarly publications, unique historical collections from the University archives, and teaching tools. The Jefferson Digital Commons allows researchers and interested readers anywhere in the world to learn about and keep up to date with Jefferson scholarship. This article has been accepted for inclusion in Abington Jefferson Health Papers by an authorized administrator of the Jefferson Digital Commons. For more information, please contact: [email protected]. Authors Faisal Inayat, Waqas Ullah, Hanan T. Lodhi, Zarak H. Khan, Ghulam Ilyas, Nouman Safdar Ali, and Hafez Mohammad A.
    [Show full text]
  • Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities
    1 Autophagy and neurodegeneration: Pathogenic mechanisms and therapeutic opportunities Fiona M Menzies1ǂ,#, Angeleen Fleming1ǂ, Andrea Caricasole2ǂ, Carla F Bento1ǂ, Steven P Andrews2ǂ, Avraham Ashkenazi1ǂ, Jens Füllgrabe1ǂ, Anne Jackson1ǂ, Maria Jimenez Sanchez1ǂ, Cansu Karabiyik1ǂ, Floriana Licitra1ǂ, Ana Lopez Ramirez1ǂ, Mariana Pavel1ǂ, Claudia Puri1ǂ, Maurizio Renna1ǂ, Thomas Ricketts1ǂ Lars Schlotawa1ǂ, Mariella Vicinanza1ǂ, Hyeran Won1ǂ, Ye Zhu1ǂ, John Skidmore2ǂ and David C Rubinsztein1* 1 Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Wellcome Trust/MRC Building, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0XY, UK. 2 Alzheimer's Research UK Cambridge Drug Discovery Institute, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge, CB2 0AH, UK. # Current address: Eli Lilly and Company Limited, Erl Wood Manor, Sunninghill Road Windlesham, Surrey, GU20 6PH, UK. ǂDenotes equal contribution *E-mail address for correspondence: [email protected] (DCR) 2 In Brief This review discusses the importance of autophagy function for brain health, outlining connections between autophagy dysfunction and neurodegenerative disorders. The potential for autophagy as a therapeutic strategy for neurodegenerative disease is discussed, along with how this may be achieved. Summary Autophagy is a conserved pathway that delivers cytoplasmic contents to the lysosome for degradation. Here we consider its roles in neuronal health and disease. We review evidence from mouse knock-out studies demonstrating the normal functions of autophagy as a protective factor against neurodegeneration associated with intracytoplasmic aggregate-prone protein accumulation, as well as other roles including in neuronal stem cell differentiation. We then describe how autophagy may be affected in a range of neurodegenerative diseases.
    [Show full text]
  • Types of Photic-Induced Seizures and Epileptic Types Associated With
    SEIZURE DISORDERS EPILEPTIC SYNDROMES AND PHOTOSENSITIVE SEIZURES The clinical features of different types of photic-induced seizures and epileptic syndromes characterized by visual sensitivity are reviewed from the University of Pisa, Italy, and Centre St Paul, Marseille, France. Seizure types associated with clinical photosensitivity include eyelid myoclonus, generalized myoclonic jerks, tonic-versive seizures, absence, generalized tonic clonic, and focal seizures. Epileptic syndromes with photic-induced seizures include benign myoclonic epilepsy in infancy, absence epilepsy, juvenile myoclonic epilepsy, epilepsy with myoclonic-astatic seizures, primary reading epilepsy, severe myoclonic epilepsy of infancy, photosensitive occipital lobe epilepsy, and progressive myoclonus epilepsies (PME). PME with photic sensitivity are symptoms of neuronal ceroid lipofuscinosis, Lafora's disease, Unverricht-Lundborg disease, and myoclonus epilepsy and ragged red fibers (MERRF). Visually induced seizures can be generalized or focal, idiopathic or symptomatic, or represent a pure reflex photosensitive epilepsy. (Guerrini R, Genton P. Epileptic syndromes and visually induced seizures. Epilepsia January 2004;45 (Suppl 1): 14- 18). (Reprints: Dr R Guerrini, Division of Child Neurology and Psychiatry, University of Pisa & IRCCS Fondazione Stella Maris, via dei Giacinti 2, 56018 Calambrone, Pisa, Italy). COMMENT. The treatment of photosensitive epilepsies involves preventive measures and antiepileptic medications (AED). (Covanis A et al. Epilepsia Jan 2004;45(Suppl l):40-45; Bureau M et al. Epilepsia Jan 2004;45(Suppl l):24-26). Preventive measures include the following: avoid stimuli (eg TV, videogames); use small TV, 100-Hz screen, remote control, sit >2 m away from screen, wear spectacles, avoid stress and fatigue. Usually a combination of avoidance of stimuli and an AED is necessary.
    [Show full text]
  • Relation of Photosensitivity to Epileptic Syndromes
    J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.49.12.1386 on 1 December 1986. Downloaded from Journal of Neurology, Neurosurgery, and Psychiatry 1986;49:1386-1391 Relation of photosensitivity to epileptic syndromes P WOLF,* R GOOSSES Abteilungfiir Neurologie, Klinikum Charlottenburg der Freien Universitdt, Berlin, Federal Republic ofGermany SUMMARY Photosensitivity is the most common mode of seizure precipitation. It is age-related, more frequent in females, and most often found in generalised epilepsies. Little is known about its relation to individual epileptic syndromes. This study on 1062 epileptic patients who had 4007 split screen video EEG investigations revealed that the relation to generalised epilepsy is even more close than generally believed. Versive seizures with visual hallucinations was the only focal seizure type related to photosensitivity. Of the syndromes of generalised epilepsy, only childhood absence epi- lepsy, juvenile myoclonic epilepsy, and epilepsy with grand mal on awakening were related to photosensitivity. The closest correlation was with juvenile myoclonic epilepsy. This is confirmed by a relation to the poly-spike wave pattern, and by an increase of myoclonic seizures by intermittent light stimuli. No relation was found with early childhood syndromes of generalised epilepsy, or generalised tonic-clonic seizures in the evening, or, most remarkably, with juvenile absence epilepsy. guest. Protected by copyright. In generalised epilepsies with onset around puberty, photosensitivity could thus act as a patho- plastic factor. The female preponderance in both childhood absences and photosensitivity could be due to the same unknown factor. Photosensitivity does not necessarily signify epi- of increasing and decreasing frequency from 3 to 30 Hz were lepsy.' In connection with epilepsy, photosensitivity applied.
    [Show full text]
  • A Type of Progressive Myoclonic Epilepsy, Lafora Disease: a Case Report
    Eastern Journal of Medicine 18 (2013) 34-36 Case Report A type of progressive myoclonic epilepsy, Lafora disease: A case report Ömer Bektaşa,*, Arzu Yılmaza, Aylin Heper Okcuc, Serap Teberb, Erhan Aksoya, Gülhis Dedaa aDepartment of Pediatric Neurology, School of Medicine, Ankara University,Turkey bDepartment of Pediatric Neurology, Dıskapı Hematology-Oncology Hospital, Turkey cDepartment of Pediatric Pathology, School of Medicine, Ankara University, Turkey Abstract. Lafora disease is a rare group of progressive myoclonic epilepsies characterized with progressive neurological dysfunction, myoclonus, focal and generalized seizures. Generally, a generalized tonic clonic seizure is the first symptom of the disease. An 11-year-old male patient had been followed-up at another center for epilepsy for 8 years. The patient had a history of myoclonic seizures for nearly every day for the last 2 years and cognitive detoriation for the last 8 months. He admitted to our hospital with the desire of his family. Eccrine sweat gland biopsy was performed. The biopsy of the sweat gland was positive for PAS and contained diastase resistant polyglican content (Lafora bodies), and thus, a diagnosis of Lafora disease was established. The patient presented here constitutes a rare case of pediatric epilepsy, which caused neurodegeneration in late-childhood and onset with typical epilepsy symptoms. This report also aimed to show that biopsy obtained from proper area is important for diagnosis Our patient developed cognitive dysfunction a short period of eight months. To our knowledge, this is the shortest period in literature. Key words: Lafora Disease, progressive myoclonic epilepsy, neurodegeneration 1. Introduction 2. Case report Progressive myoclonic epilepsy is a rare group An 11-year-old male patient had been followed- of diseases characterized with progressive up for epilepsy for 8 years.
    [Show full text]
  • Lafora Disease and Congenital Generalized Lipodystrophy: a Case Report
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector LAFORA DISEASE AND CONGENITAL GENERALIZED LIPODYSTROPHY: A CASE REPORT Chih-Fan Tseng,1 Che-Sheng Ho,1,2 Nan-Chang Chiu,1,2 Shuan-Pei Lin,1,2,3 Chi-Yuan Tzen,2,4 and Yu-Hung Wu2,5 Departments of 1Pediatrics, 3Medical Research, 4Pathology and 5Dermatology, Mackay Memorial Hospital; and 2Mackay Medicine, Nursing and Management College, Taipei, Taiwan. We report a patient with congenital generalized lipodystrophy who had suffered from seizures, myoclonus, ataxia and cognitive decline since late childhood. Lafora disease was diagnosed based on skin biopsy results, which revealed pathognomonic Lafora bodies. The results of genetic analysis for mutations in EPM2A and EPM2B genes were negative. This is the first case report describing an association between congenital generalized lipodystrophy and Lafora dis- ease. Further studies focusing on the relationship between these two diseases and the identifica- tion of a third locus for Lafora disease are needed. Key Words: Lafora disease, lipodystrophy, myoclonus, progressive myoclonic epilepsy (Kaohsiung J Med Sci 2009;25:663–8) Congenital generalized lipodystrophy (Berardinelli- develop during late childhood or adolescence. We Seip syndrome) was initially reported by Berardinelli report a child with congenital generalized lipodys- [1] and Seip [2] and is an extremely rare autosomal trophy and LD, a previously undescribed association, recessive disorder with genetic heterogeneity. Its and attempt to clarify the relationship between these prevalence has been estimated to be less than one in two diseases. one million. Three different loci (AGPAT2, BSCL2 and CAV1), which map to chromosomes 9q34, 11q13 and 7q31, respectively, have been identified [3–5].
    [Show full text]
  • A Novel Deletion Mutation in EPM2A Underlies Progressive Myoclonic Epilepsy (Lafora Body Disease) in a Pakistani Family
    Neurology Asia 2021; 26(2) : 427 – 433 A novel deletion mutation in EPM2A underlies progressive myoclonic epilepsy (Lafora body disease) in a Pakistani family 1Fizza Orooj MRCP, 2Umm-e-Kalsoom PhD, 3XiaoChu Zhao, 1Arsalan Ahmad MD, 4Imran Nazir Ahmed MD, 5Muhammad Faheem PhD, 5Muhammad Jawad Hassan PhD, 3,6Berge A. Minasian MD 1Division of Neurology, Shifa International Hospital, Shifa Tameer-e-Millat University, Islamabad, Pakistan; 2Department of Biochemistry, Hazara University, Mansehra, KPK, Pakistan; 3Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada; 4Department of Pathology, Shifa International Hospital, Shifa Tameer-e-Millat University, Islamabad, Pakistan; 5Department of Biological Sciences, National University of Medical Sciences, Rawalpindi, Pakistan; 6Department of Pediatrics, University of Texas Southwestern, Dallas, Teas, USA Abstract Lafora body disease (MIM-254780), a glycogen storage disease, characterized by Lafora bodies (deformed glycogen molecules) accumulating in multiple organs, is a rare form of myoclonic epilepsy. It manifests in early adolescent years, initially with seizures and myoclonus, followed by dementia and progressive cognitive decline, ultimately culminating in death within 10 years. In Pakistan so far 5 cases have been reported. Here, we report a new case of Lafora body disease belonging to a consanguineous family from Pakistan. Histopathological analysis confirmed presence of lafora bodies in the patient`s skin. Sanger sequencing revealed novel homozygous 5bp deletion mutation (NM_005670.4; c.359_363delGTGTG) in exon 2 of the EPM2A gene, which was truly segregated in the family. These results will increase our understanding regarding the aetiology of this disorder and will further add to the mutation spectrum of EPM2A gene.
    [Show full text]
  • The Classification of Autosomal Recessive Cerebellar Ataxias: a Consensus Statement from the Society for Research on the Cerebellum and Ataxias Task Force
    The Cerebellum (2019) 18:1098–1125 https://doi.org/10.1007/s12311-019-01052-2 CONSENSUS PAPER The Classification of Autosomal Recessive Cerebellar Ataxias: a Consensus Statement from the Society for Research on the Cerebellum and Ataxias Task Force Marie Beaudin1,2 & Antoni Matilla-Dueñas3 & Bing-Weng Soong4,5 & Jose Luiz Pedroso6 & Orlando G. Barsottini6 & Hiroshi Mitoma7 & Shoji Tsuji8,9 & Jeremy D. Schmahmann10 & Mario Manto11,12 & Guy A Rouleau13 & Christopher Klein14 & Nicolas Dupre1,2 Published online:: 2 J uly 2019 # The Author(s) 2019 Abstract There is currently no accepted classification of autosomal recessive cerebellar ataxias, a group of disorders characterized by important genetic heterogeneity and complex phenotypes. The objective of this task force was to build a consensus on the classification of autosomal recessive ataxias in order to develop a general approach to a patient presenting with ataxia, organize disorders according to clinical presentation, and define this field of research by identifying common pathogenic molecular mechanisms in these disorders. The work of this task force was based on a previously published systematic scoping review of the literature that identified autosomal recessive disorders characterized primarily by cerebellar motor dysfunction and cerebellar degeneration. The task force regrouped 12 international ataxia experts who decided on general orientation and specific issues. We identified 59 disorders that are classified as primary autosomal recessive cerebellar ataxias. For each of these disorders, we present geographical and ethnical specificities along with distinctive clinical and imagery features. These primary recessive ataxias were organized in a clinical and a pathophysiological classification, and we present a general clinical approach to the patient presenting with ataxia.
    [Show full text]
  • An Unprecedented Impact a Series of Fact Sheets on Covid-19 and Biomedical Research July 2020
    AN UNPRECEDENTED IMPACT A SERIES OF FACT SHEETS ON COVID-19 AND BIOMEDICAL RESEARCH JULY 2020 We must maintain and strengthen our nation’s investment in medical research through the National Institutes of Health. This is an urgent priority for Congress, as our nation works to restart stalled research, keep up with pressing public health challenges, continue to fightCOVID-19 and prepare for the next potential pandemic. PART 3 | PROGRESS ON HOLD | Researcher Profiles While research on the disease caused by the novel coronavirus has been on a fast track the past several months, most other medical research ground to a halt in March and has yet to resume at anything near its pre-COVID pace. It is impossible to know the full implications of suspended work, lost experiments and delayed clinical trials, but for those waiting for a cure, time matters. After 17 years of work, DR. MATTHEW GENTRY is within reach of the holy grail — a potential treatment for Lafora disease, a devastating and The episodes increase quickly, and extremely rare form of epilepsy that strikes healthy regression is pretty fast. As we still teens and takes their lives within 10 years. In March, don’t know the window of opportunity his lab was preparing to conduct one final mouse test, a crucial step toward the goal of testing treatments in to treat and find a response, every patients by next year. That’s when COVID hit and the month matters to these patients. University of Kentucky was forced to shut down all non-essential activity — including his.
    [Show full text]