Evaluation of SMN protein, transcript, and copy number in the biomarkers for spinal muscular atrophy (BforSMA) clinical study.

PloS One
Thomas O CrawfordPilot Study of Biomarkers for Spinal Muscular Atrophy Trial Group

Abstract

The universal presence of a gene (SMN2) nearly identical to the mutated SMN1 gene responsible for Spinal Muscular Atrophy (SMA) has proved an enticing incentive to therapeutics development. Early disappointments from putative SMN-enhancing agent clinical trials have increased interest in improving the assessment of SMN expression in blood as an early "biomarker" of treatment effect. A cross-sectional, single visit, multi-center design assessed SMN transcript and protein in 108 SMA and 22 age and gender-matched healthy control subjects, while motor function was assessed by the Modified Hammersmith Functional Motor Scale (MHFMS). Enrollment selectively targeted a broad range of SMA subjects that would permit maximum power to distinguish the relative influence of SMN2 copy number, SMA type, present motor function, and age. SMN2 copy number and levels of full-length SMN2 transcripts correlated with SMA type, and like SMN protein levels, were lower in SMA subjects compared to controls. No measure of SMN expression correlated strongly with MHFMS. A key finding is that SMN2 copy number, levels of transcript and protein showed no correlation with each other. This is a prospective study that uses the most advanced techniques of SMN tran...Continue Reading

Associated Clinical Trials

References

Jan 1, 1992·Neuromuscular Disorders : NMD·T L Munsat, K E Davies
Jul 1, 1997·American Journal of Human Genetics·A H Burghes
Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·B SchrankM Sendtner
Sep 27, 2001·The Journal of Biological Chemistry·J Wang, G Dreyfuss
Feb 13, 2002·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Matthew D MailmanThomas W Prior
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jul 2, 2003·Nature Genetics·Tsuyoshi Kashima, James L Manley
Sep 1, 2004·Neuromuscular Disorders : NMD·Thomas O Crawford
Dec 31, 2005·American Journal of Human Genetics·Luca CartegniAdrian R Krainer
Feb 3, 2006·BMC Neurology·Stephen J KolbGideon Dreyfuss
Jun 6, 2006·Neuromuscular Disorders : NMD·Kristin J KrosschellKathryn J Swoboda
Sep 5, 2006·Human Genetics·Virginia B MattisChristian L Lorson
Feb 20, 2007·Proceedings of the National Academy of Sciences of the United States of America·Tsuyoshi KashimaJames L Manley
Jul 25, 2007·Neurogenetics·Ilsa Gómez-CuretWenlan Wang
Nov 14, 2007·Neurology·M OskouiP Kaufmann
Mar 29, 2008·American Journal of Human Genetics·Yimin HuaAdrian R Krainer
Sep 16, 2008·PloS One·Howard Chia-Hao ChangSpyros Artavanis-Tsakonas
Nov 21, 2008·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Maryam Oskoui, Petra Kaufmann
Feb 27, 2009·RNA·Mafalda Martins de AraújoJuan Valcárcel
Jul 16, 2009·European Journal of Human Genetics : EJHG·Francesco Danilo TizianoChristina Brahe
Jul 25, 2009·Journal of Medical Genetics·B C HendricksonT Scholl
Sep 1, 2009·American Journal of Human Genetics·Thomas W PriorJohn T Kissel
Feb 18, 2010·Science Translational Medicine·Michelle L HastingsAdrian R Krainer
Mar 18, 2010·The Journal of Clinical Investigation·Marco A PassiniSeng H Cheng
Jun 12, 2010·Science Translational Medicine·Chiara F ValoriMimoun Azzouz
Sep 3, 2010·PloS One·Kathryn J SwobodaUNKNOWN Project Cure Spinal Muscular Atrophy Investigators Network
Dec 2, 2010·Human Molecular Genetics·Elisa DominguezMartine Barkats
Dec 3, 2010·PLoS Genetics·Maria DimitriadiAnne C Hart

❮ Previous
Next ❯

Citations

Aug 26, 2014·Assay and Drug Development Technologies·Jonathan J CherryJill Jarecki
Dec 4, 2014·Journal of Neuropathology and Experimental Neurology·Brian N HardingRichard S Finkel
Jan 8, 2016·Journal of Zhejiang University. Science. B·Yan-yan CaoFang Song
Jun 27, 2015·Scientific Reports·María G Boza-MoránRafael J Yáñez-Muñoz
Oct 15, 2013·American Journal of Medical Genetics. Part a·Francesco Danilo TizianoLouise R Simard
Jul 25, 2013·Annals of Human Genetics·Dian K NurputraHisahide Nishio
Aug 14, 2013·Annals of Neurology·W David Arnold, Arthur H M Burghes
May 18, 2013·Muscle & Nerve·John T KisselUNKNOWN Project Cure Spinal Muscular Atrophy Investigators Network
Jul 16, 2015·Annals of the New York Academy of Sciences·Mary H Wertz, Mustafa Sahin
Aug 8, 2015·Molecular Genetics & Genomic Medicine·Deborah L StableyMatthew E R Butchbach
Sep 3, 2013·Biochimica Et Biophysica Acta·Joonbae SeoRavindra N Singh
May 2, 2013·Molecular and Cellular Neurosciences·Andrew G L Douglas, Matthew J A Wood
Nov 22, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Michelle A Farrar, Matthew C Kiernan
Apr 8, 2015·Assay and Drug Development Technologies·Hannes SteinkellnerFranco Laccone
Jul 28, 2016·Neuromuscular Disorders : NMD·Joseph K BurnsRobin J Parks
Apr 9, 2013·PloS One·Dione T KobayashiKaren S Chen
May 5, 2012·PloS One·Richard S FinkelUNKNOWN Pilot Study of Biomarkers for Spinal Muscular Atrophy Trial Group
Nov 3, 2016·Expert Opinion on Biological Therapy·S FletcherS D Wilton
May 12, 2017·Annals of Clinical and Translational Neurology·Ulrike BonatiChristian Czech
Jan 13, 2015·Journal of Molecular Neuroscience : MN·Dario RonchiGiacomo Pietro Comi
May 2, 2013·Therapeutic Advances in Neurological Disorders·Wendy K M Liew, Peter B Kang
Feb 10, 2018·Nature Reviews. Neurology·Ewout J N GroenThomas H Gillingwater
Jan 13, 2018·Journal of Child Neurology·Gamze BoraHayat Erdem-Yurter
Nov 5, 2017·Der Nervenarzt·K VillW Müller-Felber
Dec 2, 2017·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·R I WadmanW L van der Pol
May 26, 2018·Nature Communications·Amparo Garcia-LopezLeonardo Scapozza
Jul 12, 2019·Neurology·Jennifer KollmerMarkus Weiler
Dec 29, 2019·Neurology·Christiano R R AlvesKathryn J Swoboda
Mar 24, 2020·PloS One·Maria Carmela PeraEugenio Mercuri
May 24, 2018·Human Molecular Genetics·Ewout J N GroenThomas H Gillingwater

❮ Previous
Next ❯

Methods Mentioned

BETA
SMA
antisense oligonucleotide
ELISA
PCR

Clinical Trials Mentioned

NCT00756821

Software Mentioned

SAS
Expression Analysis

Related Concepts

Related Feeds

Cajal Bodies & Gems

Cajal bodies or coiled bodies are dense foci of coilin protein. Gemini of Cajal bodies, or gems, are microscopically similar to Cajal bodies. It is believed that Cajal bodies play important roles in RNA processing while gems assist the Cajal bodies. Find the latest research on Cajal bodies and gems here.

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.