A retrospective review of the progress in amyotrophic lateral sclerosis drug discovery over the last decade and a look at the latest strategies

The C9orf72 repeat expansion itself is methylated in ALS and FTLD patients

(2015) Zhengrui Xi et al.   ACTA NEUROPATHOLOGICA

Use of biomarkers in ALS drug development and clinical trials

(2015) Nadine Bakkar et al.   BRAIN RESEARCH

ABC transporter-driven pharmacoresistance in Amyotrophic Lateral Sclerosis

(2015) Michael Jablonski et al.   BRAIN RESEARCH

Immunization with a Myelin-Derived Antigen Activates the Brain's Choroid Plexus for Recruitment of Immunoregulatory Cells to the CNS and Attenuates Disease Progression in a Mouse Model of ALS

(2015) G. Kunis et al.   JOURNAL OF NEUROSCIENCE

Haploinsufficiency of TBK1 causes familial ALS and fronto-temporal dementia

(2015) Axel Freischmidt et al.   NATURE NEUROSCIENCE

Screening a UK amyotrophic lateral sclerosis cohort provides evidence of multiple origins of the C9orf72 expansion

(2015) Pietro Fratta et al.   NEUROBIOLOGY OF AGING

Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis

(2015) C.-H. Lu et al.   NEUROLOGY

Clinical Trial Designs in Amyotrophic Lateral Sclerosis: Does One Design Fit All?

(2015) Katharine A. Nicholson et al.   Neurotherapeutics

C9ORF72 repeat expansions in mice cause TDP-43 pathology, neuronal loss, and behavioral deficits

(2015) J. Chew et al.   SCIENCE

Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways

(2015) E. T. Cirulli et al.   SCIENCE

Targeting miR-155 restores abnormal microglia and attenuates disease in SOD1 mice

(2014) Oleg Butovsky et al.   ANNALS OF NEUROLOGY

The past, present and future of stem cell clinical trials for ALS

(2014) Gretchen M. Thomsen et al.   EXPERIMENTAL NEUROLOGY

Hypermethylation of the CpG-island near the C9orf72 G4C2-repeat expansion in FTLD patients

(2014) Zhengrui Xi et al.   HUMAN MOLECULAR GENETICS

Safety and efficacy of ceftriaxone for amyotrophic lateral sclerosis: a multi-stage, randomised, double-blind, placebo-controlled trial

(2014) Merit E Cudkowicz et al.   LANCET NEUROLOGY

Clinical trials in amyotrophic lateral sclerosis: why so many negative trials and how can trials be improved?

(2014) Hiroshi Mitsumoto et al.   LANCET NEUROLOGY

Ensuring continued progress in biomarkers for amyotrophic lateral sclerosis

(2014) Martin R. Turner et al.   MUSCLE & NERVE

Analysis of the KIFAP3 gene in amyotrophic lateral sclerosis: a multicenter survival study

(2014) Perry T.C. van Doormaal et al.   NEUROBIOLOGY OF AGING

Neuronal Matrix Metalloproteinase-9 Is a Determinant of Selective Neurodegeneration

(2014) Artem Kaplan et al.   NEURON

Excess of Rare Damaging TUBA4A Variants Suggests Cytoskeletal Defects in ALS

(2014) Rosa Rademakers et al.   NEURON

Exome-wide Rare Variant Analysis Identifies TUBA4A Mutations Associated with Familial ALS

(2014) Bradley N. Smith et al.   NEURON

Dexpramipexole Is Ineffective in Two Models of ALS Related Neurodegeneration

(2014) Fernando G. Vieira et al.   PLoS One

Opportunities for improving therapy development in ALS

(2014) Lucie Bruijn et al.   Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

Inhibiting drug efflux transporters improves efficacy of ALS therapeutics

(2014) Michael R. Jablonski et al.   Annals of Clinical and Translational Neurology

Homozygosity for the C9orf72 GGGGCC repeat expansion in frontotemporal dementia

(2013) Pietro Fratta et al.   ACTA NEUROPATHOLOGICA

Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins

(2013) Kohji Mori et al.   ACTA NEUROPATHOLOGICA

Antisense transcripts of the expanded C9ORF72 hexanucleotide repeat form nuclear RNA foci and undergo repeat-associated non-ATG translation in c9FTD/ALS

(2013) Tania F. Gendron et al.   ACTA NEUROPATHOLOGICA

Reduced C9orf72 gene expression in c9FTD/ALS is caused by histone trimethylation, an epigenetic event detectable in blood

(2013) Veronique V. Belzil et al.   ACTA NEUROPATHOLOGICA

Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons

(2013) Sandra Almeida et al.   ACTA NEUROPATHOLOGICA

Altered Ribostasis: RNA-Protein Granules in Degenerative Disorders

(2013) Mani Ramaswami et al.   CELL

Back to the future: how human induced pluripotent stem cells will transform regenerative medicine

(2013) C. N. Svendsen   HUMAN MOLECULAR GENETICS

Repeat-associated non-ATG (RAN) translation in neurological disease

(2013) J. D. Cleary et al.   HUMAN MOLECULAR GENETICS

Method for widespread microRNA-155 inhibition prolongs survival in ALS-model mice

(2013) Erica D. Koval et al.   HUMAN MOLECULAR GENETICS

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

Stem cell therapy in amyotrophic lateral sclerosis

(2013) Rokhsareh Meamar et al.   JOURNAL OF CLINICAL NEUROSCIENCE

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

Dexpramipexole versus placebo for patients with amyotrophic lateral sclerosis (EMPOWER): a randomised, double-blind, phase 3 trial

(2013) Merit E Cudkowicz et al.   LANCET NEUROLOGY

Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial

(2013)   LANCET NEUROLOGY

Opportunities and challenges of pluripotent stem cell neurodegenerative disease models

(2013) Jackson Sandoe et al.   NATURE NEUROSCIENCE

Melatonin inhibits the caspase-1/cytochrome c/caspase-3 cell death pathway, inhibits MT1 receptor loss and delays disease progression in a mouse model of amyotrophic lateral sclerosis

(2013) Yi Zhang et al.   NEUROBIOLOGY OF DISEASE

The Neuroprotection Exerted by Memantine, Minocycline and Lithium, against Neurotoxicity of CSF from Patients with Amyotrophic Lateral Sclerosis, Is Antagonized by Riluzole

(2013) Matilde Yáñez et al.   Neurodegenerative Diseases

Unconventional Translation of C9ORF72 GGGGCC Expansion Generates Insoluble Polypeptides Specific to c9FTD/ALS

(2013) Peter E.A. Ash et al.   NEURON

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

(2013) Christopher J. Donnelly et al.   NEURON

The role of heat shock proteins in Amyotrophic Lateral Sclerosis: The therapeutic potential of Arimoclomol

(2013) Bernadett Kalmar et al.   PHARMACOLOGY & THERAPEUTICS

Toxic RNA as a driver of disease in a common form of ALS and dementia

(2013) H. T. Orr   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia

(2013) T. Zu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

The C9orf72 GGGGCC Repeat Is Translated into Aggregating Dipeptide-Repeat Proteins in FTLD/ALS

(2013) K. Mori et al.   SCIENCE

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

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

Functional improvement in mouse models of familial amyotrophic lateral sclerosis by PEGylated insulin-like growth factor I treatment depends on disease severity

(2012) Stefanie Saenger et al.   Amyotrophic Lateral Sclerosis

Toward an integrative view of Optineurin functions

(2012) David Kachaner et al.   CELL CYCLE

The Importance of Preclinical Trial Timing - a Potential Reason for the Disconnect between mouse Studies and Human Clinical Trials in ALS

(2012) Qiongman Kong et al.   CNS Neuroscience & Therapeutics

Liver autophagy: physiology and pathology

(2012) M. Komatsu   JOURNAL OF BIOCHEMISTRY

Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study

(2012) Elisa Majounie et al.   LANCET NEUROLOGY

Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis

(2012) Chi-Hong Wu et al.   NATURE

EPHA4 is a disease modifier of amyotrophic lateral sclerosis in animal models and in humans

(2012) Annelies Van Hoecke et al.   NATURE MEDICINE

Induced pluripotent stem cells: the new patient?

(2012) Milena Bellin et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Mutations in the PFN1 gene are not a common cause in patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration in France

(2012) Serena Lattante et al.   NEUROBIOLOGY OF AGING

Screening of the PFN1 gene in sporadic amyotrophic lateral sclerosis and in frontotemporal dementia

(2012) Cinzia Tiloca et al.   NEUROBIOLOGY OF AGING

Mutation analysis of PFN1 in familial amyotrophic lateral sclerosis patients

(2012) Hussein Daoud et al.   NEUROBIOLOGY OF AGING

A novel phosphorylation site mutation in profilin 1 revealed in a large screen of US, Nordic, and German amyotrophic lateral sclerosis/frontotemporal dementia cohorts

(2012) Caroline Ingre et al.   NEUROBIOLOGY OF AGING

Selective increase of two ABC drug efflux transporters at the blood–spinal cord barrier suggests induced pharmacoresistance in ALS

(2012) Michael R. Jablonski et al.   NEUROBIOLOGY OF DISEASE

ArrayExpress update—trends in database growth and links to data analysis tools

(2012) Gabriella Rustici et al.   NUCLEIC ACIDS RESEARCH

A Randomized, Double Blind, Placebo-Controlled Trial of Pioglitazone in Combination with Riluzole in Amyotrophic Lateral Sclerosis

(2012) Luc Dupuis et al.   PLoS One

Talampanel reduces the level of motoneuronal calcium in transgenic mutant SOD1 mice only if applied presymptomatically

(2011) Melinda Paizs et al.   Amyotrophic Lateral Sclerosis

The cytoprotective role of the Keap1–Nrf2 pathway

(2011) Liam Baird et al.   ARCHIVES OF TOXICOLOGY

Nrf2: control of sensitivity to carcinogens

(2011) Stephen L. Slocum et al.   ARCHIVES OF TOXICOLOGY

Neuroprotective effect of Nrf2/ARE activators, CDDO ethylamide and CDDO trifluoroethylamide, in a mouse model of amyotrophic lateral sclerosis

(2011) Arie Neymotin et al.   FREE RADICAL BIOLOGY AND MEDICINE

Dual neuroprotective pathways of a pro-electrophilic compound via HSF-1-activated heat-shock proteins and Nrf2-activated phase 2 antioxidant response enzymes

(2011) Takumi Satoh et al.   JOURNAL OF NEUROCHEMISTRY

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

Overexpression of Nrf2 Protects Cerebral Cortical Neurons from Ethanol-Induced Apoptotic Death

(2011) M. Narasimhan et al.   MOLECULAR PHARMACOLOGY

The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis

(2011) Merit Cudkowicz et al.   NATURE MEDICINE

Phase II screening trial of lithium carbonate in amyotrophic lateral sclerosis: Examining a more efficient trial design

(2011) R. G. Miller et al.   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

Stem cell technology for the study and treatment of motor neuron diseases

(2011) J Simon Lunn et al.   Regenerative Medicine

Current hypotheses for the underlying biology of amyotrophic lateral sclerosis

(2010) Jeffrey D. Rothstein   ANNALS OF NEUROLOGY

Safety and Immunological Effects of Mesenchymal Stem Cell Transplantation in Patients With Multiple Sclerosis and Amyotrophic Lateral Sclerosis

(2010) Dimitrios Karussis et al.   ARCHIVES OF NEUROLOGY

Mechanisms Underlying Inflammation in Neurodegeneration

(2010) Christopher K. Glass et al.   CELL

Triterpenoids CDDO-ethyl amide and CDDO-trifluoroethyl amide improve the behavioral phenotype and brain pathology in a transgenic mouse model of Huntington's disease

(2010) Cliona Stack et al.   FREE RADICAL BIOLOGY AND MEDICINE

MicroRNA-155 Promotes Autoimmune Inflammation by Enhancing Inflammatory T Cell Development

(2010) Ryan M. O'Connell et al.   IMMUNITY

Safety, Tolerability, and Pharmacokinetics of KNS-760704 (Dexpramipexole) in Healthy Adult Subjects

(2010) Michael E. Bozik et al.   JOURNAL OF CLINICAL PHARMACOLOGY

Synthetic Triterpenoid CDDO Derivatives Modulate Cytoprotective or Immunological Properties in Astrocytes, Neurons, and Microglia

(2010) David J. Graber et al.   Journal of Neuroimmune Pharmacology

Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial

(2010) Swati P Aggarwal et al.   LANCET NEUROLOGY

Non-ATG-initiated translation directed by microsatellite expansions

(2010) T. Zu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Efficacy of thalidomide for the treatment of amyotrophic lateral sclerosis: A phase II open label clinical trial

(2009) Elijah W. Stommel et al.   Amyotrophic Lateral Sclerosis

Toward more efficient clinical trials for amyotrophic lateral sclerosis

(2009) Merit E. Cudkowicz et al.   Amyotrophic Lateral Sclerosis

Erythropoietin in amyotrophic lateral sclerosis: A pilot, randomized, double-blind, placebo-controlled study of safety and tolerability

(2009) Giuseppe Lauria et al.   Amyotrophic Lateral Sclerosis

A phase II trial of talampanel in subjects with amyotrophic lateral sclerosis

(2009) Robert M. Pascuzzi et al.   Amyotrophic Lateral Sclerosis

Glatiramer acetate has no impact on disease progression in ALS at 40 mg/day: A double- blind, randomized, multicentre, placebo-controlled trial

(2009) Vincent Meininger et al.   Amyotrophic Lateral Sclerosis

Randomized sequential trial of valproic acid in amyotrophic lateral sclerosis

(2009) Sanne Piepers et al.   ANNALS OF NEUROLOGY

Motor neuronal protection by l-arginine prolongs survival of mutant SOD1 (G93A) ALS mice

(2009) Junghee Lee et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

RNA and Disease

(2009) Thomas A. Cooper et al.   CELL

Lenalidomide (Revlimid®) administration at symptom onset is neuroprotective in a mouse model of amyotrophic lateral sclerosis

(2009) Arie Neymotin et al.   EXPERIMENTAL NEUROLOGY

Foxp3-Dependent MicroRNA155 Confers Competitive Fitness to Regulatory T Cells by Targeting SOCS1 Protein

(2009) Li-Fan Lu et al.   IMMUNITY

Triterpenoid CDDO-methylamide improves memory and decreases amyloid plaques in a transgenic mouse model of Alzheimer’s disease

(2009) Magali Dumont et al.   JOURNAL OF NEUROCHEMISTRY

Long-term dietary administration of valproic acid does not affect, while retinoic acid decreases, the lifespan of G93A mice, a model for amyotrophic lateral sclerosis

(2009) Cristophe Crochemore et al.   MUSCLE & NERVE

Neuroprotective Effects of the Triterpenoid, CDDO Methyl Amide, a Potent Inducer of Nrf2-Mediated Transcription

(2009) Lichuan Yang et al.   PLoS One

Reduced expression of the Kinesin-Associated Protein 3 (KIFAP3) gene increases survival in sporadic amyotrophic lateral sclerosis

(2009) J. E. Landers et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

A novel, efficient, randomized selection trial comparing combinations of drug therapy for ALS

(2008) Paul H. Gordon et al.   Amyotrophic Lateral Sclerosis

R(+) pramipexole as a mitochondrially focused neuroprotectant: Initial early phase studies in ALS

(2008) Hua Wang et al.   Amyotrophic Lateral Sclerosis

Insulin-like growth factor-I for the treatment of amyotrophic lateral sclerosis

(2008) Stacey A. Sakowski et al.   Amyotrophic Lateral Sclerosis

Phase 2 study of sodium phenylbutyrate in ALS

(2008) Merit E. Cudkowicz et al.   Amyotrophic Lateral Sclerosis

TDP-43A315T mutation in familial motor neuron disease

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

Granulocyte-colony stimulating factor improves outcome in a mouse model of amyotrophic lateral sclerosis

(2008) Claudia Pitzer et al.   BRAIN

KNS-760704 [(6R)-4,5,6,7-tetrahydro-N6-propyl-2, 6-benzothiazole-diamine dihydrochloride monohydrate] for the Treatment of Amyotrophic Lateral Sclerosis

(2008) Valentin K. Gribkoff et al.   CNS Neuroscience & Therapeutics

Ammonium tetrathiomolybdate delays onset, prolongs survival, and slows progression of disease in a mouse model for amyotrophic lateral sclerosis

(2008) Eiichi Tokuda et al.   EXPERIMENTAL NEUROLOGY

Nordihydroguaiaretic acid increases glutamate uptake in vitro and in vivo: Therapeutic implications for amyotrophic lateral sclerosis

(2008) William Boston-Howes et al.   EXPERIMENTAL NEUROLOGY

Treatment with edaravone, initiated at symptom onset, slows motor decline and decreases SOD1 deposition in ALS mice

(2008) Hidefumi Ito et al.   EXPERIMENTAL NEUROLOGY

Mechano-growth factor, an IGF-I splice variant, rescues motoneurons and improves muscle function in SOD1G93A mice

(2008) Joanna Riddoch-Contreras et al.   EXPERIMENTAL NEUROLOGY

Late stage treatment with arimoclomol delays disease progression and prevents protein aggregation in the SOD1G93A mouse model of ALS

(2008) Bernadett Kalmar et al.   JOURNAL OF NEUROCHEMISTRY

Thalidomide causes sinus bradycardia in ALS

(2008) T. Meyer et al.   JOURNAL OF NEUROLOGY

Nuclear Erythroid 2-Related Factor 2-Antioxidative Response Element Signaling Pathway in Motor Cortex and Spinal Cord in Amyotrophic Lateral Sclerosis

(2008) Alexander Sarlette et al.   JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY

Direct Muscle Delivery of GDNF With Human Mesenchymal Stem Cells Improves Motor Neuron Survival and Function in a Rat Model of Familial ALS

(2008) Masatoshi Suzuki et al.   MOLECULAR THERAPY

Folic acid protects motor neurons against the increased homocysteine, inflammation and apoptosis in SOD1G93A transgenic mice

(2008) Xiaojie Zhang et al.   NEUROPHARMACOLOGY

Combined lithium and valproate treatment delays disease onset, reduces neurological deficits and prolongs survival in an amyotrophic lateral sclerosis mouse model

(2008) H.-L. Feng et al.   NEUROSCIENCE

Lithium delays progression of amyotrophic lateral sclerosis

(2008) F. Fornai et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Induced Pluripotent Stem Cells Generated from Patients with ALS Can Be Differentiated into Motor Neurons

(2008) J. T. Dimos et al.   SCIENCE