Genetics, Gene Therapy & Genetic Disease
- MG132‐induced progerin clearance is mediated by autophagy activation and splicing regulation
- Karim Harhouri1,
- Claire Navarro1,
- Danielle Depetris1,
- Marie‐Geneviève Mattei1,
- Xavier Nissan2,
- Pierre Cau1,3,
- Annachiara De Sandre‐Giovannoli1,4 and
- Nicolas Lévy (nicolas.levy{at}univ-amu.fr)*,1,4
- 1Aix Marseille Univ, INSERM, GMGF (Génétique Médicale et Génomique Fonctionnelle), Marseille, France
- 2CECS, I‐STEM, Institut des cellules Souches pour le Traitement et l'Etude des maladies Monogéniques, AFM, Evry, France
- 3AP‐HM, Hôpital la Timone, Service de Biologie Cellulaire, Marseille, France
- 4AP‐HM, Hôpital la Timone, Département de Génétique Médicale, Marseille, France
- ↵*Corresponding author. Tel: +33 4 91 32 48 97; Fax: +33 4 91 43 29 90; E‐mail: nicolas.levy{at}univ-amu.fr
Progerin is a toxic protein that accumulates in the nuclei of Progeria patients' cells, sequestered in abnormal PML‐NBs. The proteasome inhibitor MG132 is shown to degrade progerin by activating autophagy and transcriptional inhibition through SRSF‐1 and SRSF‐5 splicing regulation.
Synopsis
Progerin is a toxic protein that accumulates in the nuclei of Progeria patients' cells, sequestered in abnormal PML‐NBs. The proteasome inhibitor MG132 is shown to degrade progerin by activating autophagy and transcriptional inhibition through SRSF‐1 and SRSF‐5 splicing regulation.
Ubiquitinylated progerin is sequestered into abnormal ProMyelocytic Leukemia Nuclear Bodies (PML‐NBs).
Progerin reduction is based on MG132 dual action: autophagy activation and splicing regulation.
MG132 in vitro treatment rescues most of the biological hallmarks of progeria.
MG132 local treatment efficiently reduces progerin levels in vivo, in the LmnaG609G/G609G mouse model.
The powerful and dual activities of MG132 make it a promising drug towards a future and safe therapeutic development for Progeria and related Prelamin‐A processing defective diseases.
- Received November 8, 2016.
- Revision received June 2, 2017.
- Accepted June 7, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Lentiviral vectors escape innate sensing but trigger p53 in human hematopoietic stem and progenitor cells
- Francesco Piras1,2,
- Michela Riba3,
- Carolina Petrillo1,2,
- Dejan Lazarevic3,
- Ivan Cuccovillo1,
- Sara Bartolaccini1,
- Elia Stupka3,4,
- Bernhard Gentner1,
- Davide Cittaro3,
- Luigi Naldini1,2 and
- Anna Kajaste‐Rudnitski (kajaste.anna{at}hsr.it)*,1
- 1San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan, Italy
- 2Vita‐Salute San Raffaele University, Milan, Italy
- 3Center for Translational Genomics and Bioinformatics, IRCCS San Raffaele Scientific Institute, Milan, Italy
- 4Present Address: Boehringer Ingelheim, Biberach an der Riß, Germany
- ↵*Corresponding author. Tel: +39 0226435007; E‐mail: kajaste.anna{at}hsr.it
Lentiviral (LV) gene therapy vectors escape innate sensing but trigger p53 signaling in human hematopoietic stem and progenitor cells (HSPC), ultimately leading to lower engraftment of short‐term repopulating cells.
Synopsis
Lentiviral (LV) gene therapy vectors escape innate sensing but trigger p53 signaling in human hematopoietic stem and progenitor cells (HSPC), ultimately leading to lower engraftment of short‐term repopulating cells.
LV transduction remains remarkably stealth in human HSPC, avoiding innate immune activation but triggering p53 signaling in human HSPC.
p53 signaling occurs upon ATM‐dependent nuclear sensing of vector DNA (LV, IDLV, AAV) independently of integration into the host genome.
Vector‐mediated activation of p53 leads to cell cycle arrest and apoptosis ex vivo ultimately leading to lower engraftment of short‐term HSPC in vivo.
Inhibition of LV‐signaling rescues ex vivo apoptosis and early engraftment of human HSPC.
- Received April 21, 2017.
- Revision received June 6, 2017.
- Accepted June 7, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Orkambi® and amplifier co‐therapy improves function from a rare CFTR mutation in gene‐edited cells and patient tissue
- Steven V Molinski1,2,
- Saumel Ahmadi2,3,
- Wan Ip4,
- Hong Ouyang4,
- Adriana Villella5,
- John P Miller5,
- Po‐Shun Lee5,
- Kethika Kulleperuma1,2,
- Kai Du2,
- Michelle Di Paola1,2,
- Paul DW Eckford2,
- Onofrio Laselva2,
- Ling Jun Huan2,
- Leigh Wellhauser2,
- Ellen Li2,
- Peter N Ray6,
- Régis Pomès1,2,
- Theo J Moraes4,7,
- Tanja Gonska4,7,
- Felix Ratjen8 and
- Christine E Bear (bear{at}sickkids.ca)*,1,2,3
- 1Department of Biochemistry, University of Toronto, Toronto, ON, Canada
- 2Programme in Molecular Medicine, Research Institute, Hospital for Sick Children, Toronto, ON, Canada
- 3Department of Physiology, University of Toronto, Toronto, ON, Canada
- 4Programme in Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, ON, Canada
- 5Proteostasis Therapeutics, Cambridge, MA, USA
- 6Division of Molecular Genetics, Hospital for Sick Children, Toronto, ON, Canada
- 7Department of Paediatrics, University of Toronto, Toronto, ON, Canada
- 8Division of Respiratory Medicine, Hospital for Sick Children, Toronto, ON, Canada
- ↵*Corresponding author. Tel: +1 416 813 5981; E‐mail: bear{at}sickkids.ca
Potential strategies for improving function in a rare CF‐causing mutation based on a CRISPR/Cas9‐edited bronchial cell line and patient‐derived nasal cultures.
Synopsis
Potential strategies for improving function in a rare CF‐causing mutation based on a CRISPR/Cas9‐edited bronchial cell line and patient‐derived nasal cultures.
Molecular dynamic simulations predicted the consequences of the rare mutation c.3700 A>G on CFTR protein (ΔI1234_R1239‐CFTR) structure.
Misprocessing and altered function of ΔI1234_R1239‐CFTR can be partially ameliorated by small molecule modulators of ΔF508‐CFTR.
A CRISPR/Cas9‐edited HBE cell line recapitulates the endogenous expression of ΔI1234_R1239‐CFTR and response to ΔF508‐CFTR modulators.
A novel small molecule amplifier (PTI‐CH) improves the effect of the corrector (VX‐809) and potentiator (VX‐770) on ΔI1234_R1239‐CFTR in CRISPR/Cas9‐engineered and patient‐specific tissues.
- Received October 3, 2016.
- Revision received May 23, 2017.
- Accepted June 6, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Oncolytic adenovirus expressing bispecific antibody targets T‐cell cytotoxicity in cancer biopsies
- Joshua D Freedman1,
- Joachim Hagel1,
- Eleanor M Scott1,
- Ioannis Psallidas2,
- Avinash Gupta3,
- Laura Spiers3,
- Paul Miller3,
- Nikolaos Kanellakis2,
- Rebecca Ashfield4,
- Kerry D Fisher1,
- Margaret R Duffy1 and
- Leonard W Seymour (len.seymour{at}oncology.ox.ac.uk)*,1
- 1Department of Oncology, University of Oxford, Oxford, UK
- 2Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Trust, Oxford, UK
- 3Churchill Hospital, Oxford University Hospital NHS Trust, Oxford, UK
- 4Jenner Institute, University of Oxford, Oxford, UK
- ↵*Corresponding author. Tel: +44 1865 617020; E‐mail: len.seymour{at}oncology.ox.ac.uk
Oncolytic adenovirus “EnAdenotucirev” was armed to express a bispecific T‐cell engager (BiTE) targeting T cells to EpCAM+ cancer cells. This strategy mediated rapid cytotoxicity to cancer cells by tumour‐associated T cells and could overcome immune suppressive effects of malignant tumour exudates.
Synopsis
Oncolytic adenovirus “EnAdenotucirev” was armed to express a bispecific T‐cell engager (BiTE) targeting T cells to EpCAM+ cancer cells. This strategy mediated rapid cytotoxicity to cancer cells by tumour‐associated T cells and could overcome immune suppressive effects of malignant tumour exudates.
Viruses can be “armed” without losing oncolytic potency to express and secrete BiTEs only in cells supporting virus replication.
BiTE‐expressing virus can mediate targeted killing of tumour cells in clinical cancer biopsies by exogenous PBMC or endogenous T cells.
BiTE‐mediated cytotoxicity in primary malignant exudates is independent of tumour‐associated immune suppression.
- Received January 11, 2017.
- Revision received May 15, 2017.
- Accepted May 18, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- A normal genetic variation modulates synaptic MMP‐9 protein levels and the severity of schizophrenia symptoms
- Katarzyna Lepeta1,
- Katarzyna J Purzycka2,†,
- Katarzyna Pachulska‐Wieczorek2,†,
- Marina Mitjans3,
- Martin Begemann3,
- Behnam Vafadari1,
- Krystian Bijata4,
- Ryszard W Adamiak2,
- Hannelore Ehrenreich (ehrenreich{at}em.mpg.de)*,3,
- Magdalena Dziembowska (m.dziembowska{at}cent.uw.edu.pl)*,1,5 and
- Leszek Kaczmarek (l.kaczmarek{at}nencki.gov.pl)*,1
- 1Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
- 2Department of RNA Structure and Function, Institute of Bioorganic Chemistry, Poznan, Poland
- 3Clinical Neuroscience, Max Planck Institute of Experimental Medicine, DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany
- 4Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Laboratory of RNA Biology and Functional Genomics, Warsaw, Poland
- 5Laboratory of Molecular Basis of Synaptic Plasticity, Centre of New Technologies, University of Warsaw, Warsaw, Poland
- ↵*
Corresponding author. Tel: +49 551 3899 628; E‐mail: ehrenreich{at}em.mpg.de
Corresponding author. Tel: +48 22 5543 721; E‐mail: m.dziembowska{at}cent.uw.edu.pl
Corresponding author. Tel: +48 22 659 3001; E‐mail: l.kaczmarek{at}nencki.gov.pl
↵† These authors contributed equally to this work
A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients.
Synopsis
A single‐nucleotide polymorphism rs20544 located in the 3′ untranslated region of the MMP‐9 gene modulates synaptic MMP‐9 protein levels and contributes significantly to the chronic delusional syndrome in schizophrenia patients.
rs20544 MMP‐9 gene polymorphism markedly affects delusional symptoms in schizophrenic patients, without influencing overall susceptibility to the disease.
rs20544 polymorphism influences synaptic MMP‐9 activity and the morphology of dendritic spines.
rs20544 polymorphism affects MMP‐9 mRNA structure and the affinity of FMRP binding to MMP‐9 mRNA.
lower levels of MMP‐9 in the brain in Mmp‐9 heterozygous mice resulted in greater sensitivity to psychosis‐related locomotor hyperactivity.
- Received February 21, 2017.
- Revision received May 12, 2017.
- Accepted May 15, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- SPINK2 deficiency causes infertility by inducing sperm defects in heterozygotes and azoospermia in homozygotes
- Zine‐Eddine Kherraf1,†,
- Marie Christou‐Kent1,†,
- Thomas Karaouzene1,
- Amir Amiri‐Yekta1,2,3,
- Guillaume Martinez1,
- Alexandra S Vargas1,
- Emeline Lambert1,
- Christelle Borel4,
- Béatrice Dorphin5,
- Isabelle Aknin‐Seifer6,
- Michael J Mitchell7,
- Catherine Metzler‐Guillemain7,
- Jessica Escoffier1,
- Serge Nef4,
- Mariane Grepillat1,
- Nicolas Thierry‐Mieg8,
- Véronique Satre1,9,
- Marc Bailly10,11,
- Florence Boitrelle10,11,
- Karin Pernet‐Gallay12,
- Sylviane Hennebicq1,13,
- Julien Fauré2,12,
- Serge P Bottari1,14,
- Charles Coutton1,9,
- Pierre F Ray (pray{at}chu-grenoble.fr)*,1,2,‡ and
- Christophe Arnoult1,‡
- 1Genetic Epigenetic and Therapies of Infertility, Institute for Advanced Biosciences, Inserm U1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France
- 2CHU de Grenoble, UF de Biochimie Génétique et Moléculaire, Grenoble, France
- 3Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
- 4Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva 4, Switzerland
- 5Laboratoire d'Aide Médicale à la Procréation, Centre AMP 74, Contamine‐sur‐Arve, France
- 6Laboratoire de Biologie de la Reproduction, Hôpital Nord, Saint Etienne, France
- 7Aix Marseille Univ INSERM GMGF, Marseille, France
- 8Univ. Grenoble Alpes / CNRS, TIMC‐IMAG, Grenoble, France
- 9CHU de Grenoble, UF de Génétique Chromosomique, Grenoble, France
- 10Department of Reproductive Biology and Gynaecology, Poissy General Hospital, Poissy, France
- 11EA 7404 GIG, Université de Versailles Saint Quentin Montigny le Bretonneux, France
- 12Grenoble Neuroscience Institute, INSERM 1216, Grenoble, France
- 13CHU de Grenoble, UF de Biologie de la procréation, Grenoble, France
- 14CHU de Grenoble, UF de Radioanalyses, Grenoble, France
- ↵*Corresponding author. Tel: +33 4 76 76 55 73; E‐mail: pray{at}chu-grenoble.fr
SPINK2, a serine protease inhibitor, is believed to target the acrosin, the main sperm acrosomal protease. This study confirms SPINK2 in that role and finds it essential for spermiogenesis as SPINK2 deficiency induces a post meiotic block at the round spermatid stage leading to azoospermia in mice and men.
Synopsis
SPINK2, a serine protease inhibitor, is believed to target the acrosin, the main sperm acrosomal protease. This study confirms SPINK2 in that role and finds it essential for spermiogenesis as SPINK2 deficiency induces a post meiotic block at the round spermatid stage leading to azoospermia in mice and men.
In round spermatids, SPINK2 is necessary to inactivate the acrosin during its transit through the endoplasmic reticulum and the Golgi apparatus.
In the absence of SPINK2, acrosin can auto‐activate, disorganize the Golgi apparatus, prevent the production of the acrosome and induce a block at the round spermatid stage.
A reduced amount of SPINK2 in heterozygotes is also deleterious, inducing a milder phenotype of oligozoospermia and/or teratozoospermia without a systematic infertility.
- Received December 13, 2016.
- Revision received April 14, 2017.
- Accepted April 26, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- MSTO1 is a cytoplasmic pro‐mitochondrial fusion protein, whose mutation induces myopathy and ataxia in humans
- Aniko Gal1,2,
- Peter Balicza2,
- David Weaver1,
- Shamim Naghdi1,
- Suresh K Joseph1,
- Péter Várnai3,
- Tibor Gyuris4,
- Attila Horváth4,
- Laszlo Nagy4,
- Erin L Seifert1,
- Maria Judit Molnar2 and
- György Hajnóczky (gyorgy.hajnoczky{at}jefferson.edu)*,1
- 1MitoCare Center for Mitochondrial Imaging Research and Diagnostics, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA
- 2Institute of Genomic Medicine and Rare Disorders, Semmelweis University, Budapest, Hungary
- 3Department of Physiology, Semmelweis University, Budapest, Hungary
- 4Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary
- ↵*Corresponding author. Tel: +1 215 503 1427; E‐mail: gyorgy.hajnoczky{at}jefferson.edu
MSTO1 has been localized to mitochondria and linked to their morphology but its role remained unclear. Here, an MSTO1 loss‐of‐function mutation is shown to be associated with a human disorder showing mitochondrial involvement.
Synopsis
MSTO1 has been localized to mitochondria and linked to their morphology but its role remained unclear. Here, an MSTO1 loss‐of‐function mutation is shown to be associated with a human disorder showing mitochondrial involvement.
Mutation of MSTO1 is documented in a family of patients with multisystem disease.
MSTO1‐deficient patient cells and HeLa cells show impaired mitochondrial morphology and fusion that can be rescued by MSTO1 overexpression.
MSTO1 is a soluble cytoplasmic protein that likely interacts with the mitochondrial fusion proteins.
EMBO Mol Med (2017) 9: 967–984
- Received September 13, 2016.
- Revision received April 13, 2017.
- Accepted April 21, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Abnormal glycogen chain length pattern, not hyperphosphorylation, is critical in Lafora disease
- Felix Nitschke1,
- Mitchell A Sullivan1,2,
- Peixiang Wang1,
- Xiaochu Zhao1,
- Erin E Chown1,3,
- Ami M Perri1,
- Lori Israelian1,3,
- Lucia Juana‐López4,
- Paola Bovolenta5,
- Santiago Rodríguez de Córdoba4,
- Martin Steup1 and
- Berge A Minassian (berge.minassian{at}sickkids.ca)*,1,3,6
- 1Program in Genetics and Genome Biology, The Hospital for Sick Children Research Institute, Toronto, ON, Canada
- 2Glycation and Diabetes, Mater Research Institute, Translational Research Institute, The University of Queensland, Brisbane, Qld, Australia
- 3Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- 4Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas and Ciber de Enfermedades Raras, Madrid, Spain
- 5Centro de Biología Molecular Severo Ochoa, CSIC‐UAM and Ciber de Enfermedades Raras, Universidad Autónoma de Madrid, Madrid, Spain
- 6Division of Neurology, Department of Pediatrics, University of Texas Southwestern, Dallas, TX, USA
- ↵*Corresponding author. Tel: +1 416 813 6361; E‐mail: berge.minassian{at}sickkids.ca
Abnormal glycogen chain length distribution strictly correlates with glycogen accumulation and Lafora body (LB) formation in Lafora disease (LD). Against current hypotheses, neither glycogen hyperphosphorylation nor deficient general autophagy are prerequisites of the disease.
Synopsis
Abnormal glycogen chain length distribution strictly correlates with glycogen accumulation and Lafora body (LB) formation in Lafora disease (LD). Against current hypotheses, neither glycogen hyperphosphorylation nor deficient general autophagy are prerequisites of the disease.
By methodological advances chain length distribution (CLD) and phosphorylation of glycogen were determined in brain tissue confirming that overexpressed wild‐type laforin corrects the molecular phenotype in an LD mouse model.
Phosphatase‐inactive laforin does not correct glycogen hyperphosphorylation in malin‐ and laforin‐deficient mice and prevents abnormal CLD and accumulation of glycogen as well as LB formation.
Prevention of abnormal chain length distribution and accumulation of brain glycogen as well as LB formation by phosphatase‐inactive laforin is malin‐dependent as no rescue occurs in malin‐deficient mice.
General impairment of autophagy is not necessary in LD as markers of autophagic flux are not changed in any of our LD mouse models.
Laforin controls glycogen chain length distribution in a malin‐dependent fashion, and lack of this control leads to abnormal glycogen structure, glycogen accumulation, LB formation, hence to LD.
EMBO Mol Med (2017) 9: 906–917
- Received January 19, 2017.
- Revision received April 27, 2017.
- Accepted May 3, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Specific biomarkers for C9orf72 FTD/ALS could expedite the journey towards effective therapies
A hexanucleotide repeat expansion in the C9orf72 gene is a common genetic cause of ALS and FTD. The repeats are translated into five different dipeptide repeat proteins (DPRs). In this issue, Lehmer et al (2017) demonstrate that one of these DPRs, poly(GP), can be measured in the CSF of individuals with C9orf72 mutations. In conjunction with the findings from another recent study (Gendron et al, 2017), these DPR biomarkers may prove to be extremely valuable in the quest for effective therapies for C9FTD/ALS.
See also: C Lehmer et al (July 2017) and TF Gendron et al (March 2017)
Isaacs and colleagues discuss two recent studies showing how a dipeptide repeat protein, poly(GP), can be measured in the CSF of individuals with C9orf72 mutations and used as a valuable biomarker in the quest for effective therapies for C9FTD/ALS.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- DOK7 gene therapy enhances motor activity and life span in ALS model mice
- Sadanori Miyoshi1,
- Tohru Tezuka1,
- Sumimasa Arimura1,
- Taro Tomono2,3,
- Takashi Okada2 and
- Yuji Yamanashi (yyamanas{at}ims.u-tokyo.ac.jp)*,1
- 1Division of Genetics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- 2Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan
- 3Graduate School of Comprehensive Human Sciences, Majors in Medical Sciences University of Tsukuba, Ibaraki, Japan
- ↵*Corresponding author. Tel: +81 3 6409 2115; Fax: +81 3 6409 2116; E‐mail: yyamanas{at}ims.u-tokyo.ac.jp
Forced expression of DOK7 in muscle enlarges the neuromuscular junction (NMJ). Here, DOK7 gene therapy suppresses NMJ degeneration and enhances motor activity and life span in a mouse model of ALS, a progressive motor neurodegenerative disease.
Synopsis
Forced expression of DOK7 in muscle enlarges the neuromuscular junction (NMJ). Here, DOK7 gene therapy suppresses NMJ degeneration and enhances motor activity and life span in a mouse model of ALS, a progressive motor neurodegenerative disease.
DOK7 gene therapy suppresses motor nerve terminal degeneration at the neuromuscular junction (NMJ) and muscle atrophy in ALS model mice.
DOK7 gene therapy prolongs lifespan and enhances motor activity in ALS model mice.
DOK7 gene therapy, or any equivalent method that stably and safely enlarges the NMJ, has potential for treating various motor neuron diseases that manifest NMJ defects.
EMBO Mol Med (2017) 9: 880–889
- Received November 6, 2016.
- Revision received April 8, 2017.
- Accepted April 12, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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