Gene Therapy in Amyotrophic Lateral Sclerosis

The G41D mutation in SOD1-related amyotrophic lateral sclerosis exhibits phenotypic heterogeneity among individuals

(2022) Xinyi Zhao et al.   MEDICINE

Design of a Randomized, Placebo-Controlled, Phase 3 Trial of Tofersen Initiated in Clinically Presymptomatic SOD1 Variant Carriers: the ATLAS Study

(2022) Michael Benatar et al.   Neurotherapeutics

Glial Cell Dysfunction in C9orf72-Related Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

(2021) Mehdi Ghasemi et al.   Cells

Nuclear accumulation of CHMP7 initiates nuclear pore complex injury and subsequent TDP-43 dysfunction in sporadic and familial ALS

(2021) Alyssa N. Coyne et al.   Science Translational Medicine

C9orf72 ALS/FTD dipeptide repeat protein levels are reduced by small molecules that inhibit PKA or enhance protein degradation

(2021) Nausicaa V Licata et al.   EMBO JOURNAL

Suppression of mutant C9orf72 expression by a potent mixed backbone antisense oligonucleotide

(2021) Hélène Tran et al.   NATURE MEDICINE

Treatment of a Mouse Model of ALS by In Vivo Base Editing

(2020) Colin K.W. Lim et al.   MOLECULAR THERAPY

Glial Cells—The Strategic Targets in Amyotrophic Lateral Sclerosis Treatment

(2020) Tereza Filipi et al.   Journal of Clinical Medicine

Reduced C9ORF72 function exacerbates gain of toxicity from ALS/FTD-causing repeat expansion in C9orf72

(2020) Qiang Zhu et al.   NATURE NEUROSCIENCE

SOD1 Suppression with Adeno-Associated Virus and MicroRNA in Familial ALS

(2020) Christian Mueller et al.   NEW ENGLAND JOURNAL OF MEDICINE

Phase 1–2 Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS

(2020) Timothy Miller et al.   NEW ENGLAND JOURNAL OF MEDICINE

The role of TDP-43 mislocalization in amyotrophic lateral sclerosis

(2020) Terry R. Suk et al.   Molecular Neurodegeneration

Artificial MicroRNAs Targeting C9orf72 Can Reduce Accumulation of Intra-nuclear Transcripts in ALS and FTD Patients

(2019) Raygene Martier et al.   Molecular Therapy-Nucleic Acids

Psychiatric Symptoms in Amyotrophic Lateral Sclerosis: Beyond a Motor Neuron Disorder

(2019) Elisabetta Zucchi et al.   Frontiers in Neuroscience

Abnormal TDP‐43 function impairs activity‐dependent BDNF secretion, synaptic plasticity, and cognitive behavior through altered Sortilin splicing

(2019) Jason Y Tann et al.   EMBO JOURNAL

Toxic expanded GGGGCC repeat transcription is mediated by the PAF1 complex in C9orf72-associated FTD

(2019) Lindsey D. Goodman et al.   NATURE NEUROSCIENCE

Antisense Oligonucleotide Therapies for Neurodegenerative Diseases

(2019) C. Frank Bennett et al.   Annual Review of Neuroscience

Targeting RNA-Mediated Toxicity in C9orf72 ALS and/or FTD by RNAi-Based Gene Therapy

(2019) Raygene Martier et al.   Molecular Therapy-Nucleic Acids

C9orf72 intermediate expansions of 24–30 repeats are associated with ALS

(2019) Alfredo Iacoangeli et al.   Acta Neuropathologica Communications

Neurofilaments in pre-symptomatic ALS and the impact of genotype

(2019) Michael Benatar et al.   Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

Prospective natural history study of C9orf72 ALS clinical characteristics and biomarkers

(2019) Alexander J. Cammack et al.   NEUROLOGY

Pathogenic Mechanisms and Therapy Development for C9orf72 Amyotrophic Lateral Sclerosis/Frontotemporal Dementia

(2019) Jie Jiang et al.   Neurotherapeutics

Differentiation but not ALS mutations in FUS rewires motor neuron metabolism

(2019) Tijs Vandoorne et al.   Nature Communications

The deletion of mutant SOD1 via CRISPR/Cas9/sgRNA prolongs survival in an amyotrophic lateral sclerosis mouse model

(2019) Weisong Duan et al.   GENE THERAPY

CRISPR-Cas9 Screens Identify the RNA Helicase DDX3X as a Repressor of C9ORF72 (GGGGCC)n Repeat-Associated Non-AUG Translation

(2019) Weiwei Cheng et al.   NEURON

Neurofilament light: A candidate biomarker of pre-symptomatic ALS and phenoconversion

(2018) Michael Benatar et al.   ANNALS OF NEUROLOGY

Thermodynamic and spectroscopic investigations of TMPyP4 association with guanine- and cytosine-rich DNA and RNA repeats of C9orf72

(2018) Hasan Alniss et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Stress Granule Assembly Disrupts Nucleocytoplasmic Transport

(2018) Ke Zhang et al.   CELL

TDP-43 post-translational modifications in health and disease

(2018) Emanuele Buratti   EXPERT OPINION ON THERAPEUTIC TARGETS

Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons

(2018) Yingxiao Shi et al.   NATURE MEDICINE

ALS Genes in the Genomic Era and their Implications for FTD

(2018) Hung Phuoc Nguyen et al.   TRENDS IN GENETICS

C9ORF72 GGGGCC repeat-associated non-AUG translation is upregulated by stress through eIF2α phosphorylation

(2018) Weiwei Cheng et al.   Nature Communications

TDP43 nuclear export and neurodegeneration in models of amyotrophic lateral sclerosis and frontotemporal dementia

(2018) Hilary C. Archbold et al.   Scientific Reports

Mutant FUS causes DNA ligation defects to inhibit oxidative damage repair in Amyotrophic Lateral Sclerosis

(2018) Haibo Wang et al.   Nature Communications

Impeding Transcription of Expanded Microsatellite Repeats by Deactivated Cas9

(2017) Belinda S. Pinto et al.   MOLECULAR CELL

RNase H1-Dependent Antisense Oligonucleotides Are Robustly Active in Directing RNA Cleavage in Both the Cytoplasm and the Nucleus

(2017) Xue-Hai Liang et al.   MOLECULAR THERAPY

Therapeutic reduction of ataxin-2 extends lifespan and reduces pathology in TDP-43 mice

(2017) Lindsay A. Becker et al.   NATURE

C9orf72 expansion disrupts ATM-mediated chromosomal break repair

(2017) Callum Walker et al.   NATURE NEUROSCIENCE

Amyotrophic Lateral Sclerosis

(2017) Robert H. Brown et al.   NEW ENGLAND JOURNAL OF MEDICINE

Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy

(2017) Richard S. Finkel et al.   NEW ENGLAND JOURNAL OF MEDICINE

Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72 -associated amyotrophic lateral sclerosis

(2017) Tania F. Gendron et al.   Science Translational Medicine

HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients

(2017) Wenting Guo et al.   Nature Communications

SRSF1-dependent nuclear export inhibition of C9ORF72 repeat transcripts prevents neurodegeneration and associated motor deficits

(2017) Guillaume M. Hautbergue et al.   Nature Communications

Recognition of c9orf72 Mutant RNA by Single-Stranded Silencing RNAs

(2017) Jiaxin Hu et al.   Nucleic Acid Therapeutics

Antibody Therapeutics Targeting Aβ and Tau

(2017) Gilbert Gallardo et al.   Cold Spring Harbor Perspectives in Medicine

Genetics of Amyotrophic Lateral Sclerosis

(2017) Mehdi Ghasemi et al.   Cold Spring Harbor Perspectives in Medicine

CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs

(2017) Lixia Wang et al.   Protein & Cell

Genetic Correction of SOD1 Mutant iPSCs Reveals ERK and JNK Activated AP1 as a Driver of Neurodegeneration in Amyotrophic Lateral Sclerosis

(2017) Akshay Bhinge et al.   Stem Cell Reports

In vivo genome editing improves motor function and extends survival in a mouse model of ALS

(2017) Thomas Gaj et al.   Science Advances

Adeno-associated virus-delivered artificial microRNA extends survival and delays paralysis in an amyotrophic lateral sclerosis mouse model

(2016) Lorelei Stoica et al.   ANNALS OF NEUROLOGY

scAAV9-VEGF prolongs the survival of transgenic ALS mice by promoting activation of M2 microglia and the PI3K/Akt pathway

(2016) Ying Wang et al.   BRAIN RESEARCH

Physiological functions and pathobiology of TDP-43 and FUS/TLS proteins

(2016) Antonia Ratti et al.   JOURNAL OF NEUROCHEMISTRY

Intramuscular Delivery of scAAV9-hIGF1 Prolongs Survival in the hSOD1G93A ALS Mouse Model via Upregulation of D-Amino Acid Oxidase

(2016) HuiQian Lin et al.   MOLECULAR NEUROBIOLOGY

The expanding biology of the C9orf72 nucleotide repeat expansion in neurodegenerative disease

(2016) Aaron R. Haeusler et al.   NATURE REVIEWS NEUROSCIENCE

Gain of Toxicity from ALS/FTD-Linked Repeat Expansions in C9ORF72 Is Alleviated by Antisense Oligonucleotides Targeting GGGGCC-Containing RNAs

(2016) Jie Jiang et al.   NEURON

Prevalence of brain and spinal cord inclusions, including dipeptide repeat proteins, in patients with the C9ORF72 hexanucleotide repeat expansion: a systematic neuropathological review

(2016) L. J. Schipper et al.   NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY

Spt4 selectively regulates the expression of C9orf72 sense and antisense mutant transcripts

(2016) N. J. Kramer et al.   SCIENCE

Differential neuronal vulnerability identifies IGF-2 as a protective factor in ALS

(2016) Ilary Allodi et al.   Scientific Reports

Heterogeneity of cerebral TDP-43 pathology in sporadic amyotrophic lateral sclerosis: Evidence for clinico-pathologic subtypes

(2016) Ryoko Takeuchi et al.   Acta Neuropathologica Communications

Engineering Duplex RNAs for Challenging Targets: Recognition of GGGGCC/CCCCGG Repeats at the ALS/FTD C9orf72 Locus

(2015) Jiaxin Hu et al.   CHEMISTRY & BIOLOGY

Current developments in gene therapy for amyotrophic lateral sclerosis

(2015) Joseph M Scarrott et al.   EXPERT OPINION ON BIOLOGICAL THERAPY

Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles

(2015) Sven Hennig et al.   JOURNAL OF CELL BIOLOGY

Emerging mechanisms of molecular pathology in ALS

(2015) Owen M. Peters et al.   JOURNAL OF CLINICAL INVESTIGATION

The C9orf72 repeat expansion disrupts nucleocytoplasmic transport

(2015) Ke Zhang et al.   NATURE

Applications of CRISPR–Cas systems in neuroscience

(2015) Matthias Heidenreich et al.   NATURE REVIEWS NEUROSCIENCE

Silencing Mutant Huntingtin by Adeno-Associated Virus-Mediated RNA Interference Ameliorates Disease Manifestations in the YAC128 Mouse Model of Huntington's Disease

(2014) Lisa M. Stanek et al.   HUMAN GENE THERAPY

Delayed Disease Onset and Extended Survival in the SOD1G93A Rat Model of Amyotrophic Lateral Sclerosis after Suppression of Mutant SOD1 in the Motor Cortex

(2014) G. M. Thomsen et al.   JOURNAL OF NEUROSCIENCE

The role of FUS gene variants in neurodegenerative diseases

(2014) Hao Deng et al.   Nature Reviews Neurology

Discovery of a Biomarker and Lead Small Molecules to Target r(GGGGCC)-Associated Defects in c9FTD/ALS

(2014) Zhaoming Su et al.   NEURON

SOD1 Function and Its Implications for Amyotrophic Lateral Sclerosis Pathology

(2014) Rosie K. A. Bunton-Stasyshyn et al.   NEUROSCIENTIST

Allele-Specific Knockdown of ALS-Associated Mutant TDP-43 in Neural Stem Cells Derived from Induced Pluripotent Stem Cells

(2014) Agnes L. Nishimura et al.   PLoS One

Diagnostic timelines and delays in diagnosing amyotrophic lateral sclerosis (ALS)

(2014) Sabrina Paganoni et al.   Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

ALS mutant FUS disrupts nuclear localization and sequesters wild-type FUS within cytoplasmic stress granules

(2013) Caroline Vance et al.   HUMAN MOLECULAR GENETICS

TARDBPandFUSMutations Associated with Amyotrophic Lateral Sclerosis: Summary and Update

(2013) Serena Lattante et al.   HUMAN MUTATION

TMPyP4 Porphyrin Distorts RNA G-quadruplex Structures of the Disease-associated r(GGGGCC)nRepeat of theC9orf72Gene and Blocks Interaction of RNA-binding Proteins

(2013) Bita Zamiri et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study

(2013) Timothy M Miller et al.   LANCET NEUROLOGY

Genetics of amyotrophic lateral sclerosis: an update

(2013) Sheng Chen et al.   Molecular Neurodegeneration

Therapeutic AAV9-mediated Suppression of Mutant SOD1 Slows Disease Progression and Extends Survival in Models of Inherited ALS

(2013) Kevin D Foust et al.   MOLECULAR THERAPY

Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis

(2013) Shin H Kang et al.   NATURE NEUROSCIENCE

Interaction of FUS and HDAC1 regulates DNA damage response and repair in neurons

(2013) Wen-Yuan Wang et al.   NATURE NEUROSCIENCE

RNA Toxicity from the ALS/FTD C9ORF72 Expansion Is Mitigated by Antisense Intervention

(2013) Christopher J. Donnelly et al.   NEURON

Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration

(2013) C. Lagier-Tourenne et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Targeting RNA Foci in iPSC-Derived Motor Neurons from ALS Patients with a C9ORF72 Repeat Expansion

(2013) D. Sareen et al.   Science Translational Medicine

Deciphering amyotrophic lateral sclerosis: What phenotype, neuropathology and genetics are telling us about pathogenesis

(2013) John Ravits et al.   Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

Overexpression of human wild-type FUS causes progressive motor neuron degeneration in an age- and dose-dependent fashion

(2012) Jacqueline C. Mitchell et al.   ACTA NEUROPATHOLOGICA

Misfolded SOD1 and ALS: Zeroing in on mitochondria

(2012) Sarah Pickles et al.   Amyotrophic Lateral Sclerosis

Clinical characteristics of patients with familial amyotrophic lateral sclerosis carrying the pathogenic GGGGCC hexanucleotide repeat expansion of C9ORF72

(2012) A. Chio et al.   BRAIN

Clinico-pathological features in amyotrophic lateral sclerosis with expansions in C9ORF72

(2012) Johnathan Cooper-Knock et al.   BRAIN

The clinical and pathological phenotype of C9ORF72 hexanucleotide repeat expansions

(2012) Javier Simón-Sánchez et al.   BRAIN

Spt4 Is Selectively Required for Transcription of Extended Trinucleotide Repeats

(2012) Chia-Rung Liu et al.   CELL

Truncating mutations inFUS/TLSgive rise to a more aggressive ALS-phenotype than missense mutations: a clinico-genetic study in Germany

(2012) S. Waibel et al.   EUROPEAN JOURNAL OF NEUROLOGY

ALSoD: A user-friendly online bioinformatics tool for amyotrophic lateral sclerosis genetics

(2012) Olubunmi Abel et al.   HUMAN MUTATION

Phenotype difference between ALS patients with expanded repeats inC9ORF72and patients with mutations in other ALS-related genes

(2012) Stéphanie Millecamps et al.   JOURNAL OF MEDICAL GENETICS

Cognitive decline and reduced survival inC9orf72expansion frontotemporal degeneration and amyotrophic lateral sclerosis

(2012) David J Irwin et al.   JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY

Cognitive and clinical characteristics of patients with amyotrophic lateral sclerosis carrying a C9orf72 repeat expansion: a population-based cohort study

(2012) Susan Byrne et al.   LANCET NEUROLOGY

Senataxin, Defective in the Neurodegenerative Disorder Ataxia with Oculomotor Apraxia 2, Lies at the Interface of Transcription and the DNA Damage Response

(2012) O. Yuce et al.   MOLECULAR AND CELLULAR BIOLOGY

Presymptomatic studies in ALS: Rationale, challenges, and approach

(2012) M. Benatar et al.   NEUROLOGY

Knockdown of the Drosophila Fused in Sarcoma (FUS) Homologue Causes Deficient Locomotive Behavior and Shortening of Motoneuron Terminal Branches

(2012) Hiroshi Sasayama et al.   PLoS One

p62 positive, TDP-43 negative, neuronal cytoplasmic and intranuclear inclusions in the cerebellum and hippocampus define the pathology of C9orf72-linked FTLD and MND/ALS

(2011) Safa Al-Sarraj et al.   ACTA NEUROPATHOLOGICA

A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study

(2011) Ilse Gijselinck et al.   LANCET NEUROLOGY

Human Senataxin Resolves RNA/DNA Hybrids Formed at Transcriptional Pause Sites to Promote Xrn2-Dependent Termination

(2011) Konstantina Skourti-Stathaki et al.   MOLECULAR CELL

Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia

(2011) Han-Xiang Deng et al.   NATURE

Clinical genetics of amyotrophic lateral sclerosis: what do we really know?

(2011) Peter M. Andersen et al.   Nature Reviews Neurology

Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS

(2011) Mariely DeJesus-Hernandez et al.   NEURON

A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD

(2011) Alan E. Renton et al.   NEURON

Loss of murine TDP-43 disrupts motor function and plays an essential role in embryogenesis

(2010) Brian C. Kraemer et al.   ACTA NEUROPATHOLOGICA

Neurotoxic effects of TDP-43 overexpression in C. elegans

(2010) Peter E.A. Ash et al.   HUMAN MOLECULAR GENETICS

Phenotypic Heterogeneity in a SOD1 G93D Italian ALS Family: An Example of Human Model to Study a Complex Disease

(2010) Silvana Penco et al.   JOURNAL OF MOLECULAR NEUROSCIENCE

TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia

(2010) Ian RA Mackenzie et al.   LANCET NEUROLOGY

AAV4-mediated Expression of IGF-1 and VEGF Within Cellular Components of the Ventricular System Improves Survival Outcome in Familial ALS Mice

(2010) James C Dodge et al.   MOLECULAR THERAPY

Juvenile ALS with basophilic inclusions is a FUS proteinopathy with FUS mutations

(2010) D. Baumer et al.   NEUROLOGY

Spt4/5 stimulates transcription elongation through the RNA polymerase clamp coiled-coil motif

(2010) Angela Hirtreiter et al.   NUCLEIC ACIDS RESEARCH

TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration

(2010) Hans Wils et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The multiple roles of TDP-43 in pre-mRNA processing and gene expression regulation

(2010) Emanuele Buratti et al.   RNA Biology

Sustained effects of nonallele-specificHuntingtinsilencing

(2009) Valérie Drouet et al.   ANNALS OF NEUROLOGY

A new subtype of frontotemporal lobar degeneration with FUS pathology

(2009) M. Neumann et al.   BRAIN

TDP-43 Redistribution is an Early Event in Sporadic Amyotrophic Lateral Sclerosis

(2009) Maria Teresa Giordana et al.   BRAIN PATHOLOGY

Gain and loss of function of ALS-related mutations of TARDBP (TDP-43) cause motor deficits in vivo

(2009) Edor Kabashi et al.   HUMAN MOLECULAR GENETICS

The promises and pitfalls of RNA-interference-based therapeutics

(2009) Daniela Castanotto et al.   NATURE

Mutations in FUS, an RNA Processing Protein, Cause Familial Amyotrophic Lateral Sclerosis Type 6

(2009) C. Vance et al.   SCIENCE

Mutations in the FUS/TLS Gene on Chromosome 16 Cause Familial Amyotrophic Lateral Sclerosis

(2009) T. J. Kwiatkowski et al.   SCIENCE

TDP-43A315T mutation in familial motor neuron disease

(2008) Michael A. Gitcho et al.   ANNALS OF NEUROLOGY

Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis

(2008) Masato Hasegawa et al.   ANNALS OF NEUROLOGY

Structural determinants of the cellular localization and shuttling of TDP-43

(2008) Y. M. Ayala et al.   JOURNAL OF CELL SCIENCE

TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis

(2008) Vivianna M Van Deerlin et al.   LANCET NEUROLOGY

TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis

(2008) Edor Kabashi et al.   NATURE GENETICS

TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis

(2008) J. Sreedharan et al.   SCIENCE