Opportunities and Challenges for Antisense Oligonucleotide Therapies
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Amyloid Seeding of Transthyretin by Ex Vivo Cardiac Fibrils and Its
Amyloid seeding of transthyretin by ex vivo cardiac PNAS PLUS fibrils and its inhibition Lorena Saelicesa,b,c,d, Kevin Chunga,b,c,d, Ji H. Leea,b,c,d, Whitaker Cohne, Julian P. Whiteleggee, Merrill D. Bensonf, and David S. Eisenberga,b,c,d,1 aHoward Hughes Medical Institute, University of California, Los Angeles, CA 90095; bUCLA-DOE, University of California, Los Angeles, CA 90095; cDepartment of Biological Chemistry, University of California, Los Angeles, CA 90095; dMolecular Biology Institute, University of California, Los Angeles, CA 90095; eNeuropsychiatric Institute (NPI)-Semel Institute, University of California, Los Angeles, CA 90024; and fDepartment of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202 Contributed by David S. Eisenberg, April 18, 2018 (sent for review November 8, 2017; reviewed by Joel N. Buxbaum, Jeffery W. Kelly, and Gunilla T. Westermark) Each of the 30 human amyloid diseases is associated with the both full-length TTR fibrils and C-terminal TTR fragments. In aggregation of a particular precursor protein into amyloid fibrils. In type B cardiac ATTR, more distinct amyloid deposits made of transthyretin amyloidosis (ATTR), mutant or wild-type forms of the full-length TTR fibrils surround individual muscle cells. Although serum carrier protein transthyretin (TTR), synthesized and secreted the understanding of their clinical and pathological significance is by the liver, convert to amyloid fibrils deposited in the heart and incomplete, there is a clear distinction between subtypes: type A other organs. The current standard of care for hereditary ATTR is deposits display a higher capacity to recruit wild-type TTR (16). -
The Use of Ataluren in the Effective Management of Duchenne Muscular Dystrophy
Review Neuromuscular Diseases Early Diagnosis and Treatment – The Use of Ataluren in the Effective Management of Duchenne Muscular Dystrophy Eugenio Mercuri,1 Ros Quinlivan2 and Sylvie Tuffery-Giraud3 1. Catholic University, Rome, Italy; 2. Great Ormond Street Hospital and National Hospital for Neurology and Neurosurgery, London, UK; 3. Laboratory of Genetics of Rare Diseases (LGMR), University of Montpellier, Montpellier, France DOI: https://doi.org/10.17925/ENR.2018.13.1.31 he understanding of the natural history of Duchenne muscular dystrophy (DMD) is increasing rapidly and new treatments are emerging that have the potential to substantially improve the prognosis for patients with this disabling and life-shortening disease. For many, Thowever, there is a long delay between the appearance of symptoms and DMD diagnosis, which reduces the possibility of successful treatment. DMD results from mutations in the large dystrophin gene of which one-third are de novo mutations and two-thirds are inherited from a female carrier. Roughly 75% of mutations are large rearrangements and 25% are point mutations. Certain deletions and nonsense mutations can be treated whereas many other mutations cannot currently be treated. This emphasises the need for early genetic testing to identify the mutation, guide treatment and inform genetic counselling. Treatments for DMD include corticosteroids and more recently, ataluren has been approved in Europe, the first disease-modifying therapy for treating DMD caused by nonsense mutations. The use of ataluren in DMD is supported by positive results from phase IIb and phase III studies in which the treatment produced marked improvements in the 6-minute walk test, timed function tests such as the 10 m walk/run test and the 4-stair ascent/descent test compared with placebo. -
Are Speci C Symptoms and Signs That Will Enable the Clinician to Recognise Disease Patterns That Will Narrow Down the Differenti
CHILDHOOD DEVELOPMENTAL SCREENING 2020 https://doi.org/10.33591/sfp.46.5.u5 UNIT NO. 5 Brumbaugh D, Case LE, Clemens PR, Hadjiyannakis S, Pandya S, Street CHILDHOOD NEUROMUSCULAR DISORDERS examiner’s hands under the armpits and assessed for any arm periodic paralysis) and the rate of progression. An acute or delay/hypotonia, neuroimaging with MRI brain and aordable gene panels targeting neuromuscular disorders promising, with near-normal motor development in some receptor but reduced transcriptional activation and therefore 3. Orthopaedic Care neuromuscular diseases has resulted in faster and more accurate slip sign, and an attempt should be made to see if the infant can subacute onset of symptoms may be suggestive of an endocrine appropriate chromosomal/genetic testing can be considered. which are faster and less costly than whole exome or whole infants. is has resulted in new recommendations for neonatal has less side eects of other steroids. Clinical trials are still Prevention of contractures may be aected with appropriate diagnosis. Furthermore, new treatments are in the pipeline or N. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointes- A/Prof Stacey Tay Kiat Hong bear weight on both legs. e infant is then put into ventral or inammatory myositis, the chronic onset of symptoms may 2. If the child has evidence of lower limb involvement and genome sequencing. e choice of whole exome or whole newborn screening of SMA as well as a treatment algorithm for underway for head-to-head comparison of Vamorolone and resting splints of the ankles. Proper seating is also key to are already available for certain neuromuscular disorders, and 11 20 tinal and nutritional management. -
PRAC Draft Agenda of Meeting 14-17 March 2016
14 March 2016 EMA/PRAC/199507/2016 Corr.∗ Procedure Management and Committees Support Division Pharmacovigilance Risk Assessment Committee (PRAC) Draft agenda for the meeting on 14-17 March 2016 Chair: June Raine – Vice-Chair: Almath Spooner 14 March 2016, 13:00 – 19:00, room 3/A 15 March 2016, 08:30 – 19:00, room 3/A 16 March 2016, 08:30 – 19:00, room 3/A 17 March 2016, 08:30 – 16:00, room 3/E Organisational, regulatory and methodological matters (ORGAM) 31 March 2016, 10:00 - 12:00, room 7/B, via Adobe Connect Health and safety information In accordance with the Agency’s health and safety policy, delegates are to be briefed on health, safety and emergency information and procedures prior to the start of the meeting. Disclaimers Some of the information contained in this agenda is considered commercially confidential or sensitive and therefore not disclosed. With regard to intended therapeutic indications or procedure scopes listed against products, it must be noted that these may not reflect the full wording proposed by applicants and may also change during the course of the review. Additional details on some of these procedures will be published in the PRAC meeting highlights once the procedures are finalised. Of note, this agenda is a working document primarily designed for PRAC members and the work the Committee undertakes. Note on access to documents Some documents mentioned in the agenda cannot be released at present following a request for access to documents within the framework of Regulation (EC) No 1049/2001 as they are subject to on- going procedures for which a final decision has not yet been adopted. -
Annexes to the Annual Report of the European Medicines Agency 2014
Annexes to the annual report of the European Medicines Agency 2014 Table of contents Annex 1 – Members of the Management Board ............................................................................. 2 Annex 2 – Members of the Committee for Medicinal Products for Human Use ................................... 4 Annex 3 – Members of the Pharmacovigilance Risk Assessment Committee ...................................... 6 Annex 4 – Members of the Committee for Medicinal Products for Veterinary Use ............................... 8 Annex 5 – Members of the Committee on Orphan Medicinal Products ............................................ 10 Annex 6 – Members of the Committee on Herbal Medicinal Products .............................................. 12 Annex 07 – Committee for Advanced Therapies .......................................................................... 14 Annex 8 – Members of the Paediatric Committee ........................................................................ 16 Annex 9 – Working parties and working groups .......................................................................... 18 Annex 10 – CHMP opinions in 2014 on medicinal products for human use ...................................... 22 Annex 11 – CVMP opinions in 2014 on medicinal products for veterinary use .................................. 36 Annex 12 – COMP opinions in 2014 on designation of orphan medicinal products ............................ 41 Annex 13 – HMPC European Union herbal monographs in 2014.................................................... -
Innovative Therapeutic and Delivery Approaches Using Nanotechnology to Correct Splicing Defects Underlying Disease
fgene-11-00731 July 14, 2020 Time: 11:18 # 1 REVIEW published: 14 July 2020 doi: 10.3389/fgene.2020.00731 Innovative Therapeutic and Delivery Approaches Using Nanotechnology to Correct Splicing Defects Underlying Disease Marc Suñé-Pou1†, María J. Limeres2†, Cristina Moreno-Castro3, Cristina Hernández-Munain4, Josep M. Suñé-Negre1, María L. Cuestas2 and Carlos Suñé3* 1 Drug Development Service (SDM), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain, 2 Institute of Research in Microbiology and Medical Parasitology (IMPaM), Faculty of Medicine, University of Buenos Aires-CONICET, Buenos Aires, Argentina, 3 Department of Molecular Biology, Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN-CSIC), Granada, Spain, 4 Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine “López-Neyra” (IPBLN-CSIC), Granada, Spain Alternative splicing of pre-mRNA contributes strongly to the diversity of cell- and tissue- Edited by: specific protein expression patterns. Global transcriptome analyses have suggested Rosanna Asselta, Humanitas University, Italy that >90% of human multiexon genes are alternatively spliced. Alterations in the Reviewed by: splicing process cause missplicing events that lead to genetic diseases and pathologies, Dario Balestra, including various neurological disorders, cancers, and muscular dystrophies. In recent University of Ferrara, Italy Mauricio Fernando Budini, decades, research has helped to elucidate the mechanisms regulating alternative University of Chile, Chile splicing -
Curriculum Vitae
Curriculum Vitae PERSONAL INFORMATION Ulrike Schara WORK EXPERIENCE 1991- 1997 Education in Paediatrics Paediatric Outpatient Centre,City Hospital Gelsenkirchen. (Germany) Paediatric Outpatient Centre. City Hospital Gelsenkirchen.<br/>Childrens Hospital, Ruhr University Bochum<br/> 1998- 2002 Senior Neuropediatrics Children's University Hospital Bochum (Germany) . 2002- 2003 Head of Neuropediatrics Children's University Hospital Bochum (Germany) 2004- 2006 Head of Neuropediatrics Children's Hospital, City of Neuss (Germany) 2007- Present Head of the Neuropaediatric Outpatient Centre and Consultant for Neuropaediatrics University of Essen (Germany) EDUCATION AND TRAINING 1991- 2012 MD, Professor Ruhr University of Bochum, Germany University of Essen (Germany) ADDITIONAL INFORMATION Expertise Publications Publcations of the past 5 years 1.Rudnik-Schöneborn S, Tölle D, Senderek J, Eggermann K, Elbracht M, Kornak U, von der Hagen M, Kirschner J, Leube B, Müller-Felber W, Schara U, von Au K, Wieczorek D, Bußmann C, Zerres K. Diagnostic algorithms in Charcot-Marie-Tooth neuropathies: experiences from a German genetic laboratory on the basis of 1206 index patients. Clin Genet. 2016 Jan;89(1):34-43 2.Byrne S, Jansen L, U-King-Im JM, Siddiqui A, Lidov HG, Bodi I, Smith L, Mein R, Cullup T, Dionisi-Vici C, Al-Gazali L, Al-Owain M, Bruwer Z, Al Thihli K, El-Garhy R, Flanigan KM, Manickam K, Zmuda E, Banks W, Gershoni-Baruch R, Mandel H, Dagan E, Raas-Rothschild A, Barash H, Filloux F, Creel D, Harris M, Hamosh A, Kölker S, Ebrahimi-Fakhari D, Hoffmann GF, Manchester D, Boyer PJ, Manzur AY, Lourenco CM, Pilz DT, Kamath A, Prabhakar P, Rao VK, Rogers RC, Ryan MM, Brown NJ, McLean CA, Said E, Schara U, Stein A, Sewry C, Travan L, Wijburg FA, Zenker M, Mohammed S, Fanto M, Gautel M, Jungbluth H. -
Recent Advances in Oligonucleotide Therapeutics in Oncology
International Journal of Molecular Sciences Review Recent Advances in Oligonucleotide Therapeutics in Oncology Haoyu Xiong 1, Rakesh N. Veedu 2,3 and Sarah D. Diermeier 1,* 1 Department of Biochemistry, University of Otago, Dunedin 9016, New Zealand; [email protected] 2 Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Perth 6150, Australia; [email protected] 3 Perron Institute for Neurological and Translational Science, Perth 6009, Australia * Correspondence: [email protected] Abstract: Cancer is one of the leading causes of death worldwide. Conventional therapies, including surgery, radiation, and chemotherapy have achieved increased survival rates for many types of cancer over the past decades. However, cancer recurrence and/or metastasis to distant organs remain major challenges, resulting in a large, unmet clinical need. Oligonucleotide therapeutics, which include antisense oligonucleotides, small interfering RNAs, and aptamers, show promising clinical outcomes for disease indications such as Duchenne muscular dystrophy, familial amyloid neuropathies, and macular degeneration. While no approved oligonucleotide drug currently exists for any type of cancer, results obtained in preclinical studies and clinical trials are encouraging. Here, we provide an overview of recent developments in the field of oligonucleotide therapeutics in oncology, review current clinical trials, and discuss associated challenges. Keywords: antisense oligonucleotides; siRNA; aptamers; DNAzymes; cancers Citation: Xiong, H.; Veedu, R.N.; 1. Introduction Diermeier, S.D. Recent Advances in Oligonucleotide Therapeutics in According to the Global Cancer Statistics 2018, there were more than 18 million new Oncology. Int. J. Mol. Sci. 2021, 22, cancer cases and 9.6 million deaths caused by cancer in 2018 [1]. -
ALS Trial Shows Novel Therapy Is Safe | Newsroom | Washington University in St
ALS trial shows novel therapy is safe | Newsroom | Washington University in St. Louis I I] Washington University in StlDuis Contact | Media Resources & Policies | Calendar | Subscribe - ►iiii!M > ► Medicine___ & Healthcare_ ALS trial shows novel therapy is safe MEDIA CONTACTS > ► > ► Business__ &_ Law April 23, 2013 Michael Purdy > ► Science___ & Technology_ By Michael C. Purdy Senior Medical Sciences Writer (314) 286-0122 > ► Politics___ & Public Policy_ Print Forward Facebook this t: Tweet this Share more [email protected] > ► Culture__ & Living_ > ► Visual____ & Performing Arts_ An investigational > ► __ Athletics treatment for an RELATED CONTENT inherited form of Lou Gehrig’s disease has » News for the Categories Record WUSTL Community passed an early phase clinical trial for safety, Medicine & Healthcare researchers at Record: University News FOLLOW US > ► Washington University School of Medicine in St. Schools Louis and Massachusetts School of Medicine Facebook General Hospital report. Topics The researchers have Twitter shown that the therapy ALS, Lou Gehrig's disease, produced no serious side amyotrophic lateral sclerosis, effects in patients with antisense, Hope Center, Timothy YouTube the disease, also known Miller, Merit Cudkowicz as amyotrophic lateral sclerosis (ALS). The RSS phase 1 trial’s results, available online in Lancet Neurology, also FUTURITY demonstrate that the drug was successfully VIEW ALL introduced into the central nervous system. The treatment uses a technique that shuts off the mutated gene that causes the disease. This approach had never been tested against a condition MATTHEW J. CRISP that damages nerve cells A mutated protein that causes an inherited form of in the brain and spinal Lou Gehrig’s disease leads to clumps in the cord. -
(2018) ISSN 2541-108X I
Seminar Kimia Surakarta, December 8th, 2017 Proceeding of Chemistry Conferences vol. 3 (2018) ISSN 2541-108X i Seminar Kimia Surakarta, December 8th, 2017 Proceeding of Chemistry Conferences vol. 3 (2018) ISSN 2541-108X CONTENTS Cover i Contents ii Welcoming speech iii Organizing committee iv List of article in prosiding v ii Seminar Kimia Surakarta, December 8th, 2017 Proceeding of Chemistry Conferences vol. 3 (2018) ISSN 2541-108X Welcome Speech from Committee and Head of Chemistry Department Sebelas Maret University It is a great pleasure that I could take a part in the special event of Seminar Kimia 2017 held by Departement of Chemistry, Sebelas Maret University. This event is attended by students and purposes to encourage the research and study motivation of the students. Some of the attendance presented a valuable and reviews of the recent research paper in the poster session. The presented article was then compiled and published in the Proceeding of Chemistry Conferences vol 3 (2018). We do hope the meeting and the proceeding will provide a significant contribution to science and technology especially in the Chemistry field to foster a more supportive academic aura. Surakarta, June 2018 Head of Chemistry Department UNS Chairman Dr.Triana Kusumaningsih, M.Si Teguh Endah Saraswati, M.Sc., Ph.D iii Seminar Kimia Surakarta, December 8th, 2017 Proceeding of Chemistry Conferences vol. 3 (2018) ISSN 2541-108X ORGANIZING COMMITTEE OF Lectures and Workshop: In Series of Nanotechnology and Nanomaterial Plasma Science and Technology for Nanomaterial Engineering November 3-4, 2016 Conference Advisory Board: • Dr. Triana Kusumaningsih (Sebelas Maret University, Indonesia) • Dr. -
Current Status of Microrna-Based Therapeutic Approaches in Neurodegenerative Disorders
cells Review Current Status of microRNA-Based Therapeutic Approaches in Neurodegenerative Disorders Sujay Paul *, Luis Alberto Bravo Vázquez y, Samantha Pérez Uribe y, Paula Roxana Reyes-Pérez y and Ashutosh Sharma * Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, Av. Epigmenio Gonzalez, No. 500 Fracc. San Pablo, Querétaro CP 76130, Mexico; [email protected] (L.A.B.V.); [email protected] (S.P.U.); [email protected] (P.R.R.-P.) * Correspondence: [email protected] (S.P.); [email protected] (A.S.) These authors have contributed equally to this work. y Received: 1 June 2020; Accepted: 3 July 2020; Published: 15 July 2020 Abstract: MicroRNAs (miRNAs) are a key gene regulator and play essential roles in several biological and pathological mechanisms in the human system. In recent years, plenty of miRNAs have been identified to be involved in the development of neurodegenerative disorders (NDDs), thus making them an attractive option for therapeutic approaches. Hence, in this review, we provide an overview of the current research of miRNA-based therapeutics for a selected set of NDDs, either for their high prevalence or lethality, such as Alzheimer’s, Parkinson’s, Huntington’s, Amyotrophic Lateral Sclerosis, Friedreich’s Ataxia, Spinal Muscular Atrophy, and Frontotemporal Dementia. We also discuss the relevant delivery techniques, pertinent outcomes, their limitations, and their potential to become a new generation of human therapeutic drugs in the near future. Keywords: MicroRNA; neurodegenerative disorders; miRNA therapeutics; miRNA delivery 1. Introduction MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate post-transcriptional gene expression by directing target mRNA cleavage or translational inhibition. -
Antisense Therapy for Cancer
REVIEWS ANTISENSE THERAPY FOR CANCER Martin E. Gleave* and Brett P. Monia‡ Abstract | Improved understanding of the molecular mechanisms that mediate cancer progression and therapeutic resistance has identified many therapeutic gene targets that regulate apoptosis, proliferation and cell signalling. Antisense oligonucleotides offer one approach to target genes involved in cancer progression, especially those that are not amenable to small-molecule or antibody inhibition. Better chemical modifications of antisense oligonucleotides increase resistance to nuclease digestion, prolong tissue half-lives and improve scheduling. Indeed, recent clinical trials confirm the ability of this class of drugs to significantly suppress target-gene expression. The current status and future directions of several antisense drugs that have potential clinical use in cancer are reviewed. 1 PHOSPHOROTHIOATE Zamecnik and Stephenson ushered in the era of anti- nucleotide sequences of cancer-relevant genes offer the BACKBONE sense therapeutics when they reported that an oligo- possibility to rapidly design ASO or short interfering The non-bridging phosphoryl nucleotide complementary to the 3′ end of the Rous RNA (siRNA) duplexes for loss-of-function studies and oxygen of each nucleotide in an sarcoma virus could block viral replication in chicken preclinical proof of principle. Automated DNA synthe- oligomer is replaced with sulphur, which increases fibroblasts. An antisense oligonucleotide (ASO) is a sis and advances in the field of nucleic-acid chemistry resistance to nuclease digestion single-stranded, chemically modified DNA-like mol- have facilitated progress in the use of this technology and prolongs tissue half-life. ecule that is 17–22 nucleotides in length and designed for target validation and therapy.