Small molecule splicing modifiers with systemic HTT-lowering activity

Huntingtin-Lowering Therapies for Huntington Disease

(2020) Blair R. Leavitt et al.   JAMA Neurology

Risdiplam: First Approval

(2020) Sohita Dhillon   DRUGS

Discovery of a CNS penetrant small molecule SMN2 splicing modulator with improved tolerability for spinal muscular atrophy

(2020) Shiori Ando et al.   Scientific Reports

Huntingtin Lowering Strategies for Disease Modification in Huntington’s Disease

(2019) Sarah J. Tabrizi et al.   NEURON

Allele-selective transcriptional repression of mutant HTT for the treatment of Huntington’s disease

(2019) Bryan Zeitler et al.   NATURE MEDICINE

Structural basis of a small molecule targeting RNA for a specific splicing correction

(2019) Sébastien Campagne et al.   Nature Chemical Biology

Discovery of Risdiplam, a Selective Survival of Motor Neuron-2 (SMN2) Gene Splicing Modifier for the Treatment of Spinal Muscular Atrophy (SMA)

(2018) Hasane Ratni et al.   JOURNAL OF MEDICINAL CHEMISTRY

Huntingtin suppression restores cognitive function in a mouse model of Huntington’s disease

(2018) Amber L. Southwell et al.   Science Translational Medicine

Therapies targeting DNA and RNA in Huntington's disease

(2017) Edward J Wild et al.   LANCET NEUROLOGY

Binding to SMN2 pre-mRNA-protein complex elicits specificity for small molecule splicing modifiers

(2017) Manaswini Sivaramakrishnan et al.   Nature Communications

Huntington's disease (HD): the neuropathology of a multisystem neurodegenerative disorder of the human brain

(2016) U. Rüb et al.   BRAIN PATHOLOGY

Specific Correction of Alternative Survival Motor Neuron 2 Splicing by Small Molecules: Discovery of a Potential Novel Medicine To Treat Spinal Muscular Atrophy

(2016) Hasane Ratni et al.   JOURNAL OF MEDICINAL CHEMISTRY

The Biology of Huntingtin

(2016) Frédéric Saudou et al.   NEURON

Ablation of huntingtin in adult neurons is nondeleterious but its depletion in young mice causes acute pancreatitis

(2016) Guohao Wang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Treating the whole body in Huntington's disease

(2015) Jeffrey B Carroll et al.   LANCET NEUROLOGY

SMN2 splice modulators enhance U1–pre-mRNA association and rescue SMA mice

(2015) James Palacino et al.   Nature Chemical Biology

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

SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy

(2014) N. A. Naryshkin et al.   SCIENCE

TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions

(2013) Daehwan Kim et al.   GENOME BIOLOGY

STAR: ultrafast universal RNA-seq aligner

(2012) Alexander Dobin et al.   BIOINFORMATICS

A fully humanized transgenic mouse model of Huntington disease

(2012) Amber L. Southwell et al.   HUMAN MOLECULAR GENETICS

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

(2012) Holly B. Kordasiewicz et al.   NEURON

A Screen for Enhancers of Clearance Identifies Huntingtin as a Heat Shock Protein 90 (Hsp90) Client Protein

(2011) Barbara Baldo et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Membrane transporters in drug development

(2010)   NATURE REVIEWS DRUG DISCOVERY

Full-Length Human Mutant Huntingtin with a Stable Polyglutamine Repeat Can Elicit Progressive and Selective Neuropathogenesis in BACHD Mice

(2008) M. Gray et al.   JOURNAL OF NEUROSCIENCE