Targets for future clinical trials in Huntington's disease: What's in the pipeline?

Genetic deletion of PDE10A selectively impairs incentive salience attribution and decreases medium spiny neuron excitability

(2014) Elisabeth Piccart et al.   BEHAVIOURAL BRAIN RESEARCH

HTT-lowering reverses Huntington’s disease immune dysfunction caused by NFκB pathway dysregulation

(2014) Ulrike Träger et al.   BRAIN

Oligonucleotide-based therapy for neurodegenerative diseases

(2014) Iddo Magen et al.   BRAIN RESEARCH

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

A potent and selective Sirtuin 1 inhibitor alleviates pathology in multiple animal and cell models of Huntington's disease

(2014) Marianne R. Smith et al.   HUMAN MOLECULAR GENETICS

Foundation-Directed Therapeutic Development in Huntington’s Disease

(2014) Celia Dominguez et al.   JOURNAL OF MEDICINAL CHEMISTRY

Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington's disease

(2014) Nan Wang et al.   NATURE MEDICINE

Huntington disease: natural history, biomarkers and prospects for therapeutics

(2014) Christopher A. Ross et al.   Nature Reviews Neurology

Increased Brain Penetration and Potency of a Therapeutic Antibody Using a Monovalent Molecular Shuttle

(2014) Jens Niewoehner et al.   NEURON

A Monoclonal Antibody TrkB Receptor Agonist as a Potential Therapeutic for Huntington’s Disease

(2014) Daniel Todd et al.   PLoS One

Influence of diverse chemical modifications on the ADME characteristics and toxicology of antisense oligonucleotides

(2013) Mehrdad Dirin et al.   EXPERT OPINION ON BIOLOGICAL THERAPY

Silencing human genetic diseases with oligonucleotide-based therapies

(2013) Tamara Martínez et al.   HUMAN GENETICS

Small-molecule TrkB receptor agonists improve motor function and extend survival in a mouse model of Huntington's disease

(2013) M. Jiang et al.   HUMAN MOLECULAR GENETICS

Neuroprotective effects of PPAR-γ agonist rosiglitazone in N171-82Q mouse model of Huntington's disease

(2013) Jing Jin et al.   JOURNAL OF NEUROCHEMISTRY

MAP Kinase Phosphatase 1 (MKP-1/DUSP1) Is Neuroprotective in Huntington's Disease via Additive Effects of JNK and p38 Inhibition

(2013) D. M. Taylor et al.   JOURNAL OF NEUROSCIENCE

A Small Molecule TrkB Ligand Reduces Motor Impairment and Neuropathology in R6/2 and BACHD Mouse Models of Huntington's Disease

(2013) D. A. Simmons et al.   JOURNAL OF 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

Parkinson's Disease Gene Therapy: Success by Design Meets Failure by Efficacy

(2013) Raymond T Bartus et al.   MOLECULAR THERAPY

Exogenous delivery of chaperonin subunit fragment ApiCCT1 modulates mutant Huntingtin cellular phenotypes

(2013) E. M. Sontag et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease

(2013) K. Sathasivam et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

HDAC4 Reduction: A Novel Therapeutic Strategy to Target Cytoplasmic Huntingtin and Ameliorate Neurodegeneration

(2013) Michal Mielcarek et al.   PLOS BIOLOGY

Reduced astrocytic NF-κB activation by laquinimod protects from cuprizone-induced demyelination

(2012) Wolfgang Brück et al.   ACTA NEUROPATHOLOGICA

Kinetics of Proinflammatory Monocytes in a Model of Multiple Sclerosis and Its Perturbation by Laquinimod

(2012) Manoj K. Mishra et al.   AMERICAN JOURNAL OF PATHOLOGY

Six-month partial suppression of Huntingtin is well tolerated in the adult rhesus striatum

(2012) Richard Grondin et al.   BRAIN

Suppression of protein aggregation by chaperone modification of high molecular weight complexes

(2012) John Labbadia et al.   BRAIN

Single-Stranded RNAs Use RNAi to Potently and Allele-Selectively Inhibit Mutant Huntingtin Expression

(2012) Dongbo Yu et al.   CELL

Single-Stranded siRNAs Activate RNAi in Animals

(2012) Walt F. Lima et al.   CELL

Oral treatment with laquinimod augments regulatory T-cells and brain-derived neurotrophic factor expression and reduces injury in the CNS of mice with experimental autoimmune encephalomyelitis

(2012) Rina Aharoni et al.   JOURNAL OF NEUROIMMUNOLOGY

Cannabinoid Receptor 2 Signaling in Peripheral Immune Cells Modulates Disease Onset and Severity in Mouse Models of Huntington's Disease

(2012) J. Bouchard et al.   JOURNAL OF NEUROSCIENCE

Kynurenines in the CNS: recent advances and new questions

(2012) László Vécsei et al.   NATURE REVIEWS DRUG DISCOVERY

Histone deacetylase (HDAC) inhibitors targeting HDAC3 and HDAC1 ameliorate polyglutamine-elicited phenotypes in model systems of Huntington's disease

(2012) Haiqun Jia et al.   NEUROBIOLOGY OF DISEASE

“Huntingtin Holiday”: Progress toward an Antisense Therapy for Huntington's Disease

(2012) Xiao-Hong Lu et al.   NEURON

Sustained Therapeutic Reversal of Huntington's Disease by Transient Repression of Huntingtin Synthesis

(2012) Holly B. Kordasiewicz et al.   NEURON

Hunting Down Huntingtin

(2012) Neil Aronin et al.   NEW ENGLAND JOURNAL OF MEDICINE

Placebo-Controlled Trial of Oral Laquinimod for Multiple Sclerosis

(2012) Giancarlo Comi et al.   NEW ENGLAND JOURNAL OF MEDICINE

Genetic Knock-Down of Hdac3 Does Not Modify Disease-Related Phenotypes in a Mouse Model of Huntington's Disease

(2012) Lara Moumné et al.   PLoS One

Ganglioside GM1 induces phosphorylation of mutant huntingtin and restores normal motor behavior in Huntington disease mice

(2012) A. Di Pardo et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Synthetic zinc finger repressors reduce mutant huntingtin expression in the brain of R6/2 mice

(2012) M. Garriga-Canut et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A Pathogenic Mechanism in Huntington's Disease Involves Small CAG-Repeated RNAs with Neurotoxic Activity

(2012) Mónica Bañez-Coronel et al.   PLoS Genetics

Kynurenine 3-Monooxygenase Inhibition in Blood Ameliorates Neurodegeneration

(2011) Daniel Zwilling et al.   CELL

The Kynurenine Pathway Modulates Neurodegeneration in a Drosophila Model of Huntington's Disease

(2011) Susanna Campesan et al.   CURRENT BIOLOGY

Immune Responses to AAV in Clinical Trials

(2011) Federico Mingozzi et al.   CURRENT GENE THERAPY

Widespread suppression of huntingtin with convection-enhanced delivery of siRNA

(2011) David K. Stiles et al.   EXPERIMENTAL NEUROLOGY

Rational Design of Therapeutic siRNAs: Minimizing Off-targeting Potential to Improve the Safety of RNAi Therapy for Huntington's Disease

(2011) Ryan L Boudreau et al.   MOLECULAR THERAPY

Potent and Selective Antisense Oligonucleotides Targeting Single-Nucleotide Polymorphisms in the Huntington Disease Gene / Allele-Specific Silencing of Mutant Huntingtin

(2011) Jeffrey B Carroll et al.   MOLECULAR THERAPY

Preclinical Safety of RNAi-Mediated HTT Suppression in the Rhesus Macaque as a Potential Therapy for Huntington's Disease

(2011) Jodi L McBride et al.   MOLECULAR THERAPY

In vivo genome editing restores haemostasis in a mouse model of haemophilia

(2011) Hojun Li et al.   NATURE

Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes

(2011) Lydia Alvarez-Erviti et al.   NATURE BIOTECHNOLOGY

Kinase inhibitors modulate huntingtin cell localization and toxicity

(2011) Randy Singh Atwal et al.   Nature Chemical Biology

Neuroprotective role of Sirt1 in mammalian models of Huntington's disease through activation of multiple Sirt1 targets

(2011) Mali Jiang et al.   NATURE MEDICINE

P38 MAPK is involved in enhanced NMDA receptor-dependent excitotoxicity in YAC transgenic mouse model of Huntington disease

(2011) Jing Fan et al.   NEUROBIOLOGY OF DISEASE

Hdac6 Knock-Out Increases Tubulin Acetylation but Does Not Modify Disease Progression in the R6/2 Mouse Model of Huntington's Disease

(2011) Anna Bobrowska et al.   PLoS One

Targeting Several CAG Expansion Diseases by a Single Antisense Oligonucleotide

(2011) Melvin M. Evers et al.   PLoS One

SAHA Decreases HDAC 2 and 4 Levels In Vivo and Improves Molecular Phenotypes in the R6/2 Mouse Model of Huntington's Disease

(2011) Michal Mielcarek et al.   PLoS One

RNA Targeting Therapeutics: Molecular Mechanisms of Antisense Oligonucleotides as a Therapeutic Platform

(2010) C. Frank Bennett et al.   Annual Review of Pharmacology and Toxicology

Chemical Inducers of Autophagy That Enhance the Clearance of Mutant Proteins in Neurodegenerative Diseases

(2010) Maurizio Renna et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Role of Excitatory Amino Acid Transporter-2 (EAAT2) and glutamate in neurodegeneration: Opportunities for developing novel therapeutics

(2010) Keetae Kim et al.   JOURNAL OF CELLULAR PHYSIOLOGY

Impaired Ganglioside Metabolism in Huntington's Disease and Neuroprotective Role of GM1

(2010) V. Maglione et al.   JOURNAL OF NEUROSCIENCE

Chronic Suppression of Phosphodiesterase 10A Alters Striatal Expression of Genes Responsible for Neurotransmitter Synthesis, Neurotransmission, and Signaling Pathways Implicated in Huntington's Disease

(2010) R. J. Kleiman et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial

(2010) William J Marks et al.   LANCET NEUROLOGY

Huntington's disease: from molecular pathogenesis to clinical treatment

(2010) Christopher A Ross et al.   LANCET NEUROLOGY

Cargo recognition failure is responsible for inefficient autophagy in Huntington's disease

(2010) Marta Martinez-Vicente et al.   NATURE NEUROSCIENCE

Inhibition of the Striatal Specific Phosphodiesterase PDE10A Ameliorates Striatal and Cortical Pathology in R6/2 Mouse Model of Huntington's Disease

(2010) Carmela Giampà et al.   PLoS One

A small-molecule scaffold induces autophagy in primary neurons and protects against toxicity in a Huntington disease model

(2010) A. S. Tsvetkov et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A majority of Huntington's disease patients may be treatable by individualized allele-specific RNA interference

(2009) Maria Stella Lombardi et al.   EXPERIMENTAL NEUROLOGY

Altered P2X7-receptor level and function in mouse models of Huntington’s disease and therapeutic efficacy of antagonist administration

(2009) Miguel Díaz-Hernández et al.   FASEB JOURNAL

Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin

(2009) Gerardo A Morfini et al.   NATURE NEUROSCIENCE

Serines 13 and 16 Are Critical Determinants of Full-Length Human Mutant Huntingtin Induced Disease Pathogenesis in HD Mice

(2009) Xiaofeng Gu et al.   NEURON

Genetic Knock-Down of HDAC7 Does Not Ameliorate Disease Pathogenesis in the R6/2 Mouse Model of Huntington's Disease

(2009) Caroline L. Benn et al.   PLoS One

Phosphorylation of mutant huntingtin at S421 restores anterograde and retrograde transport in neurons

(2008) Diana Zala et al.   HUMAN MOLECULAR GENETICS

A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease

(2008) Maria Björkqvist et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Inhibition of Phosphodiesterase 10A Increases the Responsiveness of Striatal Projection Neurons to Cortical Stimulation

(2008) S. Threlfell et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

CEP-1347 reduces mutant huntingtin-associated neurotoxicity and restores BDNF levels in R6/2 mice

(2008) Barbara L. Apostol et al.   MOLECULAR AND CELLULAR NEUROSCIENCE

Beneficial effects of rolipram in the R6/2 mouse model of Huntington's disease

(2008) Zena DeMarch et al.   NEUROBIOLOGY OF DISEASE

Up-regulation of GLT1 expression increases glutamate uptake and attenuates the Huntington's disease phenotype in the R6/2 mouse

(2008) B.R. Miller et al.   NEUROSCIENCE