Genomes and Genes
Timothy M Miller
Affiliation: Washington University School of Medicine
- Gene-targeted therapies for the central nervous systemTimothy M Miller
Neurosciences Department, University of California, San Diego, San Diego, California, USA
Arch Neurol 65:447-51. 2008
- An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man studyTimothy M Miller
Washington University School of Medicine, St Louis, MO, USA
Lancet Neurol 12:435-42. 2013..We aimed to assess the safety, tolerability, and pharmacokinetics of ISIS 333611 after intrathecal administration in patients with SOD1-related familial amyotrophic lateral sclerosis...
- Antisense oligonucleotide therapy for neurodegenerative diseaseRichard A Smith
Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, California, USA
J Clin Invest 116:2290-6. 2006..This suggests that direct delivery of antisense oligonucleotides could be an effective, dosage-regulatable means of treating neurodegenerative diseases, including ALS, where appropriate target proteins are known...
- Amyotrophic lateral sclerosis and gene therapyTimothy M Miller
Department of Neurosciences, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093 0670, USA
Nat Clin Pract Neurol 2:462-3. 2006
- TREM2 variant p.R47H as a risk factor for sporadic amyotrophic lateral sclerosisJanet Cady
Department of Neurology, Washington University School of Medicine, St Louis, Missouri
JAMA Neurol 71:449-53. 2014..R47H) in the microglial activating gene TREM2 was found to increase the risk of several neurodegenerative diseases, including Alzheimer disease. Whether the p.R47H variant is a risk factor for ALS is not known...
- ALS-linked mutant superoxide dismutase 1 (SOD1) alters mitochondrial protein composition and decreases protein importQuan Li
Department of Neurology, Hope Center for Neurological Disorders, The Washington University School of Medicine, St Louis, MO 63110, USA
Proc Natl Acad Sci U S A 107:21146-51. 2010..Thus, altered mitochondrial protein content accompanied by selective decreases in protein import into spinal cord mitochondria comprises part of the mitochondrial damage arising from mutant SOD1...
- Virus-delivered small RNA silencing sustains strength in amyotrophic lateral sclerosisTimothy M Miller
Ludwig Institute for Cancer Research, University of California, San Diego, USA
Ann Neurol 57:773-6. 2005....
- Progressive spinal axonal degeneration and slowness in ALS2-deficient miceKoji Yamanaka
Ludwig Institute for Cancer Research and Department of Medicine and Neurosciences, University of California, San Diego, La Jolla, 92093 0670, USA
Ann Neurol 60:95-104. 2006..The goal of this study was to elucidate how the motor system is affected by the deletion of ALS2...
- SOD1 in cerebral spinal fluid as a pharmacodynamic marker for antisense oligonucleotide therapyLeah Winer
Department of Neurology, Washington University, St Louis, Missouri 63110, USA
JAMA Neurol 70:201-7. 2013..Therapies designed to decrease the level of SOD1 are currently in a clinical trial for patients with superoxide dismutase (SOD1)-linked familial amyotrophic lateral sclerosis (ALS)...
- Canine degenerative myelopathy: biochemical characterization of superoxide dismutase 1 in the first naturally occurring non-human amyotrophic lateral sclerosis modelMatthew J Crisp
Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
Exp Neurol 248:1-9. 2013..Our findings lend strong biochemical support to the toxic role of SOD1 in canine degenerative myelopathy and establish close parallels for the role mutant SOD1 plays in both canine and human disorders. ..
- TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degenerationIga Wegorzewska
Department of Neurology and Hope Center for Neurological Diseases, Washington University School of Medicine, St Louis, MO 63110, USA
Proc Natl Acad Sci U S A 106:18809-14. 2009....
- Familial ALS with extreme phenotypic variability due to the I113T SOD1 mutationGlenn Lopate
Washington University School of Medicine, Department of Neurology, Saint Louis, Missouri 63110, USA
Amyotroph Lateral Scler 11:232-6. 2010..This family highlights the extreme variability in age of onset, clinical manifestations, disease progression and penetrance due to the I113T SOD1 mutation...
- Tau Prion Strains Dictate Patterns of Cell Pathology, Progression Rate, and Regional Vulnerability In VivoSarah K Kaufman
Program in Neuroscience, Washington University in St Louis, St Louis, MO 63130, USA Center for Alzheimer s and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA0, USA
Neuron 92:796-812. 2016..Further study of these strains can thus establish a structural logic that governs these biological effects...
- Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathySarah L DeVos
Department of Neurology, Hope Center for Neurological Disorders, Washington University in St Louis, St Louis, MO 63110, USA
Sci Transl Med 9:. 2017..These data support investigation of a tau-lowering therapy in human patients who have tau-positive inclusions even after pathological tau deposition has begun...
- Distinct tau prion strains propagate in cells and mice and define different tauopathiesDavid W Sanders
Department of Neurology, Washington University in St Louis, St Louis, MO 63105, USA
Neuron 82:1271-88. 2014..Tau thus demonstrates essential characteristics of a prion. This might explain the phenotypic diversity of tauopathies and could enable more effective diagnosis and therapy...
- Muscle crampsTimothy M Miller
Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0670, USA
Muscle Nerve 32:431-42. 2005..Patients will benefit from further studies to better define the pathophysiology of muscle cramps and to find more effective medications with fewer side-effects...
- Medicine. Treating neurodegenerative diseases with antibioticsTimothy M Miller
Ludwig Institute for Cancer Research and the Department of Medicine and Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA
Science 307:361-2. 2005
- Should the Babinski sign be part of the routine neurologic examination?Timothy M Miller
Department of Neurology, University of California, San Francisco, CA, USA
Neurology 65:1165-8. 2005..A less well-known sign of upper motor neuron dysfunction, decreased speed of foot tapping, also has not been carefully evaluated. Scientific evaluation of findings of the physical examination is crucial in directing busy clinicians...
- Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seedsBrandon B Holmes
Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
Proc Natl Acad Sci U S A 110:E3138-47. 2013..Finally, uptake and seeding by α-synuclein fibrils, but not huntingtin fibrils, occurs by the same mechanism as tau. This work suggests a unifying mechanism of cell uptake and propagation for tauopathy and synucleinopathy. ..
- Antisense oligonucleotides: treating neurodegeneration at the level of RNASarah L DeVos
Department of Neurology, Washington University in St Louis School of Medicine, St Louis, MO 63110, USA
Neurotherapeutics 10:486-97. 2013..Although still early in development, translating ASOs into human patients for neurodegeneration appears promising. ..
- Antisense reduction of tau in adult mice protects against seizuresSarah L DeVos
Department of Neurology, Hope Center for Neurological Disorders, Washington University, St Louis, Missouri 63110, USA
J Neurosci 33:12887-97. 2013....
- Management of amyotrophic lateral sclerosisTaha Bali
Neuromuscular Disease Division, Washington University School of Medicine, St Louis, USA
Mo Med 110:417-21. 2013..The diagnosis is made clinically, supported by electrodiagnostic testing. Although medications are limited, careful attention to breathing, nutrition, and patient mobility can have a major, positive impact on the course of the disease...
- Differential diagnosis of myotonic disordersTimothy M Miller
Neurology Department, Washington University, St Louis, MI, USA
Muscle Nerve 37:293-9. 2008..Acid maltase deficiency often produces myotonic potentials without clinical evidence of myotonia or paramyotonia. The differential diagnosis of these myotonic disorders is discussed...
- Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondriaJian Liu
Ludwig Institute for Cancer Research, Department of Neurosciences, Medicine, and Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Neuron 43:5-17. 2004..These findings implicate damage from action of spinal cord-specific factors that recruit mutant SOD1 to spinal mitochondria as the basis for their selective toxicity in ALS...
- Proposed modification to data analysis for statistical motor unit number estimateTimothy M Miller
Department of Neurology, University of California San Francisco, San Francisco, California, USA
Muscle Nerve 29:700-6. 2004....
- Gene transfer demonstrates that muscle is not a primary target for non-cell-autonomous toxicity in familial amyotrophic lateral sclerosisTimothy M Miller
Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA
Proc Natl Acad Sci U S A 103:19546-51. 2006..Thus, SOD1-mutant-mediated damage within muscles is not a significant contributor to non-cell-autonomous pathogenesis in ALS, and enhancing muscle mass and strength provides no benefit in slowing disease onset or progression...
- Has gene therapy for ALS arrived?Timothy M Miller
Nat Med 9:1256-7. 2003