Overview

My laboratory develops new treatments for neurodegenerative diseases such as Huntington’s disease. We do this by first developing transgenic mouse models of specific human diseases, and then by testing new disease treatments in these mouse models. The YAC128 mouse model of Huntington’s disease accurately replicates the changes seen in humans with this disease, and is a critical tool that permits my laboratory to evaluate new treatment strategies in mice prior to undertaking large-scale clinical trials in human patients. Currently, my work is primarily focused on transgenic mouse models of Huntington’s disease, but in the future will expand to utilize the same standardized approach to investigate new therapeutics in mouse models of other devastating neurodegenerative disorders, such as ALS, prion disease, Parkinson's, and Alzheimer's disease.

Publications

Author Correction: The current landscape of nucleic acid therapeutics
Nature Nanotechnology
Jayesh A. Kulkarni and Dominik Witzigmann and Sarah B. Thomson and Sam Chen and Blair R. Leavitt and Pieter R. Cullis and Roy van der Meel
DOI: 10.1038/s41565-021-00937-w
07/2021

Safety and feasibility of research lumbar puncture in Huntington’s disease: the HDClarity cohort and bioresource
Filipe B Rodrigues and Gail Owen and Swati Sathe and Elena Pak and Dipinder Kaur and Anka G Ehrhardt and Sherry Lifer and Jenny Townhill and Katarzyna Schubert and Blair R Leavitt and Mark Guttman and Jee Bang and Jan Lewerenz and Jamie Levey and Cristina Sampaio and Edward J Wild
DOI: 10.1101/2021.07.30.21261340
07/2021

The current landscape of nucleic acid therapeutics
Nature Nanotechnology
Jayesh A. Kulkarni and Dominik Witzigmann and Sarah B. Thomson and Sam Chen and Blair R. Leavitt and Pieter R. Cullis and Roy van der Meel
DOI: 10.1038/s41565-021-00898-0
06/2021

Composite UHDRS Correlates With Progression of Imaging Biomarkers in Huntington's Disease
Movement Disorders
Carlos Estevez-Fraga and Rachael I. Scahill and Alexandra Durr and Blair R. Leavitt and Raymund A.C. Roos and Douglas R. Langbehn and Geraint Rees and Sarah Gregory and Sarah J. Tabrizi
DOI: 10.1002/mds.28489
05/2021

Huntingtin-Lowering Therapies for Huntington Disease: A Review of the Evidence of Potential Benefits and Risks.
JAMA neurology
DOI: 10.1001/jamaneurol.2020.0299
PubMed: 32202594
03/2020

Longitudinal Structural MRI in Neurologically Healthy Adults
Journal of magnetic resonance imaging : JMRI
Gregory, Sarah and Lohse, Keith R and Johnson, Eileanoir B and Leavitt, Blair R and Durr, Alexandra and Roos, Raymund A C and Rees, Geraint and Tabrizi, Sarah J and Scahill, Rachael I and Orth, Michael
DOI: 10.1002/jmri.27203
2020

Spontaneous, solvent-free entrapment of siRNA within lipid nanoparticles
Nanoscale
Jayesh A. Kulkarni and Sarah B. Thomson and Josh Zaifman and Jerry Leung and Pamela K. Wagner and Austin Hill and Yuen Yi C. Tam and Pieter R. Cullis and Terri L. Petkau and Blair R. Leavitt
DOI: 10.1039/D0NR06816K
2020

Apathy predicts rate of cognitive decline over 24 months in premanifest Huntington's disease
Psychological medicine
Andrews, SC and Langbehn, DR and Craufurd, D and Durr, A and Leavitt, BR and Roos, RA and Tabrizi, SJ and Stout, JC and {TRACK-HD Investigators}
DOI: 10.1017/s0033291720000094
2020

Antisense oligonucleotides for neurodegeneration
Science (New York, N.Y.)
Leavitt, Blair R and Tabrizi, Sarah J
DOI: 10.1126/science.aba4624
2020

Early deficits in olfaction are associated with structural and molecular alterations in the olfactory system of a Huntington disease mouse model
Human molecular genetics
Laroche, M and Lessard-Beaudoin, M and Garcia-Miralles, M and Kreidy, C and Peachey, Emma and Leavitt, Blair R and Pouladi, MA and Graham, RK
DOI: 10.1093/hmg/ddaa099
2020

A genetic association study of glutamine-encoding DNA sequence structures, somatic CAG expansion, and DNA repair gene variants, with Huntington disease clinical outcomes.
EBioMedicine
DOI: 10.1016/j.ebiom.2019.09.020
PubMed: 31607598
10/2019

Movement Disorder Society Task Force Viewpoint: Huntington's Disease Diagnostic Categories.
Movement Disorders Clinical Practice
DOI: 10.1002/mdc3.12808
PubMed: 31538087
08/2019

Association of CAG Repeats With Long-term Progression in Huntington Disease.
JAMA neurology
DOI: 10.1001/jamaneurol.2019.2368
PubMed: 31403680
08/2019

Targeting Huntingtin Expression in Patients with Huntington's Disease.
The New England journal of medicine
DOI: 10.1056/nejmoa1900907
PubMed: 31059641
05/2019

Huntingtin Lowering Strategies for Disease Modification in Huntington's Disease
Neuron
Tabrizi, Sarah J and Ghosh, Rhia and Leavitt, Blair R
DOI: 10.1016/j.neuron.2019.01.039
2019

Mutant huntingtin expression in microglia is neither required nor sufficient to cause the Huntington's disease-like phenotype in BACHD mice
Human molecular genetics
Petkau, Terri L and Hill, Austin and Connolly, Colúm and Lu, Ge and Wagner, Pam and Kosior, Natalia and Blanco, Jake and Leavitt, Blair R
DOI: 10.1093/hmg/ddz009
2019

Isolating cells from adult murine brain for validation of cell-type specific cre-mediated deletion
Journal of neuroscience methods
Kosior, Natalia and Petkau, Terri L and Connolly, Colúm and Lu, Ge and Leavitt, Blair R
DOI: 10.1016/j.jneumeth.2019.108422
2019

Executive impairment is associated with unawareness of neuropsychiatric symptoms in premanifest and early Huntington’s disease.
Neuropsychology
Sophie C. Andrews and David Craufurd and Alexandra Durr and Blair R. Leavitt and Raymund A. Roos and Sarah J. Tabrizi and Julie C. Stout
DOI: 10.1037/neu0000479
11/2018

Transcriptional Regulation of the Huntingtin Gene.
Journal of Huntington's disease
DOI: 10.3233/jhd-180331
PubMed: 30452421
01/2018

Computational Analysis of Transcriptional Regulation Sites at the HTT Gene Locus.
Journal of Huntington's disease
DOI: 10.3233/jhd-170272
PubMed: 30103339
01/2018

Neurofilament light protein in blood predicts regional atrophy in Huntington disease.
Neurology
DOI: 10.1212/wnl.0000000000005005
PubMed: 29367444
01/2018

Editorial on Clinical Trial's Corner.
Journal of Huntington's disease
DOI: 10.3233/jhd-189000
PubMed: 29504545
01/2018

Testing a longitudinal compensation model in premanifest Huntington's disease
Brain : a journal of neurology
Gregory, Sarah and Long, Jeffrey D and Klöppel, Stefan and Razi, Adeel and Scheller, Elisa and Minkova, Lora and Johnson, Eileanoir B and Durr, Alexandra and Roos, Raymund A C and Leavitt, Blair R and Mills, James A and Stout, Julie C and Scahill, Rachael I and Tabrizi, Sarah J and Rees, Geraint and {Track-On investigators}
DOI: 10.1093/brain/awy122
2018

Cross-sectional and longitudinal voxel-based grey matter asymmetries in Huntington's disease
NeuroImage. Clinical
Minkova, Lora and Gregory, Sarah and Scahill, Rachael I and Abdulkadir, Ahmed and Kaller, Christoph P and Peter, Jessica and Long, Jeffrey D and Stout, Julie C and Reilmann, Ralf and Roos, Raymund A and Durr, Alexandra and Leavitt, Blair R and Tabrizi, Sarah J and Klöppel, Stefan and {TRACK-HD Investigators}
DOI: 10.1016/j.nicl.2017.10.023
2018

Brain Regions Showing White Matter Loss in Huntington's Disease Are Enriched for Synaptic and Metabolic Genes
Biological Psychiatry
McColgan, Peter and Gregory, Sarah and Seunarine, Kiran K and Razi, Adeel and Papoutsi, Marina and Johnson, Eileanoir and Durr, Alexandra and Roos, Raymund A C and Leavitt, Blair R and Holmans, Peter and Scahill, Rachael I and Clark, Chris A and Rees, Geraint and Tabrizi, Sarah J and {Track-On HD Investigators}
DOI: 10.1016/j.biopsych.2017.10.019
2018

Murine Models of Huntington's Disease for Evaluating Therapeutics
Methods in molecular biology (Clifton, N.J.)
Kosior, Natalia and Leavitt, Blair R
DOI: 10.1007/978-1-4939-7825-0_10
2018

Altered Intracortical T1-Weighted/T2-Weighted Ratio Signal in Huntington's Disease
Frontiers in neuroscience
Rowley, Christopher D and Tabrizi, Sarah J and Scahill, Rachael I and Leavitt, Blair R and Roos, Raymund A C and Durr, Alexandra and Bock, Nicholas A
DOI: 10.3389/fnins.2018.00805
2018

Selective depletion of microglial progranulin in mice is not sufficient to cause neuronal ceroid lipofuscinosis or neuroinflammation.
Journal of neuroinflammation
DOI: 10.1186/s12974-017-1000-9
PubMed: 29149899
11/2017

Survival End Points for Huntington Disease Trials Prior to a Motor Diagnosis.
JAMA neurology
DOI: 10.1001/jamaneurol.2017.2107
PubMed: 28975278
11/2017

Conditional loss of progranulin in neurons is not sufficient to cause neuronal ceroid lipofuscinosis-like neuropathology in mice
Neurobiology of Disease
Terri L. Petkau and Jake Blanco and Blair R. Leavitt
DOI: 10.1016/j.nbd.2017.06.012
10/2017

Design optimization for clinical trials in early-stage manifest Huntington's disease.
Movement disorders : official journal of the Movement Disorder Society
DOI: 10.1002/mds.27122
PubMed: 28906031
09/2017

KEAP1-modifying small molecule reveals muted NRF2 signaling responses in neural stem cells from Huntington's disease patients.
Proceedings of the National Academy of Sciences of the United States of America
DOI: 10.1073/pnas.1614943114
PubMed: 28533375
05/2017

p35 hemizygosity activates Akt but does not improve motor function in the YAC128 mouse model of Huntington's disease.
Neuroscience
DOI: 10.1016/j.neuroscience.2017.03.051
PubMed: 28391013
04/2017

Structural and functional brain network correlates of depressive symptoms in premanifest Huntington's disease.
Human brain mapping
DOI: 10.1002/hbm.23527
PubMed: 28294457
03/2017

Epidemiology of Huntington disease.
Handbook of clinical neurology
DOI: 10.1016/b978-0-12-801893-4.00003-1
PubMed: 28947124
01/2017

Validation of Ultrasensitive Mutant Huntingtin Detection in Human Cerebrospinal Fluid by Single Molecule Counting Immunoassay.
Journal of Huntington's disease
DOI: 10.3233/jhd-170269
PubMed: 29125493
01/2017

White matter predicts functional connectivity in premanifest Huntington's disease.
Annals of clinical and translational neurology
DOI: 10.1002/acn3.384
PubMed: 28168210
01/2017

Introducing the "Clinical Trials Corner"
Journal of Huntington's disease
Leavitt, Blair R and Thompson, Leslie M
DOI: 10.3233/jhd-179003
2017

Operationalizing compensation over time in neurodegenerative disease
Brain : a journal of neurology
Gregory, Sarah and Long, Jeffrey D and Klöppel, Stefan and Razi, Adeel and Scheller, Elisa and Minkova, Lora and Papoutsi, Marina and Mills, James A and Durr, Alexandra and Leavitt, Blair R and Roos, Raymund A C and Stout, Julie C and Scahill, Rachael I and Langbehn, Douglas R and Tabrizi, Sarah J and Rees, Geraint
DOI: 10.1093/brain/awx022
2017

Topological length of white matter connections predicts their rate of atrophy in premanifest Huntington's disease
JCI insight
McColgan, Peter and Seunarine, Kiran K and Gregory, Sarah and Razi, Adeel and Papoutsi, Marina and Long, Jeffrey D and Mills, James A and Johnson, Eileanoir and Durr, Alexandra and Roos, Raymund Ac and Leavitt, Blair R and Stout, Julie C and Scahill, Rachael I and Clark, Chris A and Rees, Geraint and Tabrizi, Sarah J and {Track-On HD Investigators}
DOI: 10.1172/jci.insight.92641
2017

Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington's disease: a retrospective cohort analysis
The Lancet. Neurology
Byrne, Lauren M and Rodrigues, Filipe B and Blennow, Kaj and Durr, Alexandra and Leavitt, Blair R and Roos, Raymund A C and Scahill, Rachael I and Tabrizi, Sarah J and Zetterberg, Henrik and Langbehn, Douglas and Wild, Edward J
DOI: 10.1016/s1474-4422(17)30124-2
2017

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study
The Lancet. Neurology
Moss, Davina J Hensman and Pardiñas, Antonio F and Langbehn, Douglas and Lo, Kitty and Leavitt, Blair R and Roos, Raymund and Durr, Alexandra and Mead, Simon and {TRACK-HD investigators} and {REGISTRY investigators} and Holmans, Peter and Jones, Lesley and Tabrizi, Sarah J
DOI: 10.1016/s1474-4422(17)30161-8
2017

The reliability of commonly used electrophysiology measures
Brain stimulation
Brown, KE and Lohse, KR and Mayer, IMS and Strigaro, G and Desikan, M and Casula, EP and Meunier, S and Popa, T and Lamy, J-C and Odish, O and Leavitt, BR and Durr, A and Roos, RAC and Tabrizi, SJ and Rothwell, JC and Boyd, LA and Orth, M
DOI: 10.1016/j.brs.2017.07.011
2017

Recommendations for the Use of Automated Gray Matter Segmentation Tools: Evidence from Huntington's Disease
Frontiers in neurology
Johnson, Eileanoir B and Gregory, Sarah and Johnson, Hans J and Durr, Alexandra and Leavitt, Blair R and Roos, Raymund A and Rees, Geraint and Tabrizi, Sarah J and Scahill, Rachael I
DOI: 10.3389/fneur.2017.00519
2017

Motor, cognitive, and functional declines contribute to a single progressive factor in early HD
Neurology
Schobel, Scott A and Palermo, Giuseppe and Auinger, Peggy and Long, Jeffrey D and Ma, Shiyang and Khwaja, Omar S and Trundell, Dylan and Cudkowicz, Merit and Hersch, Steven and Sampaio, Cristina and Dorsey, E Ray and Leavitt, Blair R and Kieburtz, Karl D and Sevigny, Jeffrey J and Langbehn, Douglas R and Tabrizi, Sarah J and {TRACK-HD, COHORT, CARE-HD, and 2CARE Huntington Study Group Investigators}
DOI: 10.1212/wnl.0000000000004743
2017

Potential biomarkers to follow the progression and treatment response of Huntington's disease.
The Journal of experimental medicine
DOI: 10.1084/jem.20160776
PubMed: 27821553
11/2016

Natural variation in sensory-motor white matter organization influences manifestations of Huntington's disease.
Human brain mapping
DOI: 10.1002/hbm.23332
PubMed: 27477323
08/2016

Visuospatial Processing Deficits Linked to Posterior Brain Regions in Premanifest and Early Stage Huntington's Disease.
Journal of the International Neuropsychological Society : JINS
DOI: 10.1017/s1355617716000321
PubMed: 27211109
05/2016

Enhanced immune response to MMP3 stimulation in microglia expressing mutant huntingtin.
Neuroscience
DOI: 10.1016/j.neuroscience.2016.03.031
PubMed: 27033979
03/2016

Large-scale brain network abnormalities in Huntington's disease revealed by structural covariance
Human Brain Mapping
Minkova, Lora and Eickhoff, Simon B and Abdulkadir, Ahmed and Kaller, Christoph P and Peter, Jessica and Scheller, Elisa and Lahr, Jacob and Roos, Raymund A and Durr, Alexandra and Leavitt, Blair R and Tabrizi, Sarah J and Klöppel, Stefan and {TRACK-HD Investigators}
DOI: 10.1002/hbm.23014
2016

Core neuropathological abnormalities in progranulin-deficient mice are penetrant on multiple genetic backgrounds
Neuroscience
Petkau, TL and Hill, A and Leavitt, BR
DOI: 10.1016/j.neuroscience.2015.12.006
2016

DNA methylation profiling in human Huntington's disease brain
Human molecular genetics
De Souza, Rebecca A G and Islam, Sumaiya A and McEwen, Lisa M and Mathelier, Anthony and Hill, Austin and Mah, Sarah M and Wasserman, Wyeth W and Kobor, Michael S and Leavitt, Blair R
DOI: 10.1093/hmg/ddw076
2016

Cerebrospinal fluid total tau concentration predicts clinical phenotype in Huntington's disease
Journal of neurochemistry
Rodrigues, Filipe Brogueira and Byrne, Lauren and McColgan, Peter and Robertson, Nicola and Tabrizi, Sarah J and Leavitt, Blair R and Zetterberg, Henrik and Wild, Edward J
DOI: 10.1111/jnc.13719
2016

Compensation in Preclinical Huntington's Disease: Evidence From the Track-On HD Study.
EBioMedicine
DOI: 10.1016/j.ebiom.2015.08.002
PubMed: 26629536
08/2015

Direct intracerebral delivery of a miR-33 antisense oligonucleotide into mouse brain increases brain ABCA1 expression. [Corrected].
Neuroscience letters
DOI: 10.1016/j.neulet.2015.05.007
PubMed: 25957561
05/2015

Huntington disease.
Nature Reviews. Disease Primers
DOI: 10.1038/nrdp.2015.5
PubMed: 27188817
04/2015

Neurobiology of Huntington's Disease.
Current topics in behavioral neurosciences
DOI: 10.1007/7854_2014_353
PubMed: 25205327
01/2015

Reliability and factor structure of the Short Problem Behaviors Assessment for Huntington's disease (PBA-s) in the TRACK-HD and REGISTRY studies.
The Journal of neuropsychiatry and clinical neurosciences
DOI: 10.1176/appi.neuropsych.13070169
PubMed: 25716488
01/2015

Detection of Motor Changes in Huntington's Disease Using Dynamic Causal Modeling
Frontiers in human neuroscience
Minkova, Lora and Scheller, Elisa and Peter, Jessica and Abdulkadir, Ahmed and Kaller, Christoph P and Roos, Raymund A and Durr, Alexandra and Leavitt, Blair R and Tabrizi, Sarah J and Klöppel, Stefan and {TrackOn-HD Investigators}
DOI: 10.3389/fnhum.2015.00634
2015

Characterisation of immune cell function in fragment and full-length Huntington's disease mouse models
Neurobiology of disease
Träger, Ulrike and Andre, Ralph and Magnusson-Lind, Anna and Miller, James R C and Connolly, Colúm and Weiss, Andreas and Grueninger, Stephan and Silajdžic, Edina and Smith, Donna L and Leavitt, Blair R and Bates, Gillian P and Björkqvist, Maria and Tabrizi, Sarah J
DOI: 10.1016/j.nbd.2014.10.012
2015

Safety, tolerability, and efficacy of PBT2 in Huntington's disease: a phase 2, randomised, double-blind, placebo-controlled trial
The Lancet. Neurology
{Huntington Study Group Reach2HD Investigators}
DOI: 10.1016/s1474-4422(14)70262-5
2015

Treatment of Huntington Disease and Comorbid Trichotillomania With Aripiprazole
The Journal of neuropsychiatry and clinical neurosciences
Howard, Andrew K and Krishnamoorthy, Ashok and Leavitt, Blair R and Raymond, Lynn A and Weissman, Cory R
DOI: 10.1176/appi.neuropsych.14090232
2015

Indoleamine 2,3 Dioxygenase as a Potential Therapeutic Target in Huntington's Disease
Journal of Huntington's disease
Mazarei, Gelareh and Leavitt, Blair R
DOI: 10.3233/jhd-159003
2015

A longitudinal study of magnetic resonance spectroscopy Huntington's disease biomarkers
Movement disorders : official journal of the Movement Disorder Society
Sturrock, Aaron and Laule, Corree and Wyper, Katy and Milner, Ruth A and Decolongon, Joji and Dar Santos, Rachelle and Coleman, Allison J and Carter, Kimberley and Creighton, Susan and Bechtel, Natalie and Bohlen, Stefan and Reilmann, Ralf and Johnson, Hans J and Hayden, Michael R and Tabrizi, Sarah J and Mackay, Alex L and Leavitt, Blair R
DOI: 10.1002/mds.26118
2015

Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington's disease patients
The Journal of clinical investigation
Wild, Edward J and Boggio, Roberto and Langbehn, Douglas and Robertson, Nicola and Haider, Salman and Miller, James R C and Zetterberg, Henrik and Leavitt, Blair R and Kuhn, Rainer and Tabrizi, Sarah J and Macdonald, Douglas and Weiss, Andreas
DOI: 10.1172/jci80743
2015

A SNP in the HTT promoter alters NF-¿B binding and is a bidirectional genetic modifier of Huntington disease
Nature neuroscience
Becanovic, Kristina and Nørremølle, Anne and Neal, Scott J and Kay, Chris and Collins, Jennifer A and Arenillas, David and Lilja, Tobias and Gaudenzi, Giulia and Manoharan, Shiana and Doty, Crystal N and Beck, Jessalyn and Lahiri, Nayana and Portales-Casamar, Elodie and Warby, Simon C and Connolly, Colúm and De Souza, Rebecca A G and {REGISTRY Investigators of the European Huntington's Disease Network} and Tabrizi, Sarah J and Hermanson, Ola and Langbehn, Douglas R and Hayden, Michael R and Wasserman, Wyeth W and Leavitt, Blair R
DOI: 10.1038/nn.4014
2015

Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression
Scientific reports
Southwell, Amber L and Smith, Stephen E P and Davis, Tessa R and Caron, Nicholas S and Villanueva, Erika B and Xie, Yuanyun and Collins, Jennifer A and Ye, Min Li and Sturrock, Aaron and Leavitt, Blair R and Schrum, Adam G and Hayden, Michael R
DOI: 10.1038/srep12166
2015

The impact of occipital lobe cortical thickness on cognitive task performance: An investigation in Huntington's Disease
Neuropsychologia
Johnson, Eileanoir B and Rees, Elin M and Labuschagne, Izelle and Durr, Alexandra and Leavitt, Blair R and Roos, Raymund A C and Reilmann, Ralf and Johnson, Hans and Hobbs, Nicola Z and Langbehn, Douglas R and Stout, Julie C and Tabrizi, Sarah J and Scahill, Rachael I and {TRACK-HD investigators}
DOI: 10.1016/j.neuropsychologia.2015.10.033
2015

Proteolytic degradation of neuropeptide Y (NPY) from head to toe: Identification of novel NPY-cleaving peptidases and potential drug interactions in CNS and Periphery
Journal of neurochemistry
Wagner, Leona and Wolf, Raik and Zeitschel, Ulrike and Rossner, Steffen and Petersén, Åsa and Leavitt, Blair R and Kästner, Florian and Rothermundt, Matthias and Gärtner, Ulf-Torsten and Gündel, Daniel and Schlenzig, Dagmar and Frerker, Nadine and Schade, Jutta and Manhart, Susanne and Rahfeld, Jens-Ulrich and Demuth, Hans-Ulrich and von Hörsten, Stephan
DOI: 10.1111/jnc.13378
2015

Huntington's disease: a field on the move. Introduction.
Movement disorders : official journal of the Movement Disorder Society
DOI: 10.1002/mds.26017
PubMed: 25164859
08/2014

The catalytic function of hormone-sensitive lipase is essential for fertility in male mice.
Endocrinology
DOI: 10.1210/en.2014-1031
PubMed: 24797631
05/2014

Iron dysregulation in Huntington's disease.
Journal of neurochemistry
DOI: 10.1111/jnc.12739
PubMed: 24717009
05/2014

Correction of inter-scanner and within-subject variance in structural MRI based automated diagnosing.
NeuroImage
DOI: 10.1016/j.neuroimage.2014.04.057
PubMed: 24791746
04/2014

Huntington disease: natural history, biomarkers and prospects for therapeutics.
Nature reviews. Neurology
DOI: 10.1038/nrneurol.2014.24
PubMed: 24614516
03/2014

The potential of composite cognitive scores for tracking progression in Huntington's disease.
Journal of Huntington's disease
DOI: 10.3233/jhd-140101
PubMed: 25062862
01/2014

Progranulin in neurodegenerative disease
Trends in neurosciences
Petkau, Terri L and Leavitt, Blair R
DOI: 10.1016/j.tins.2014.04.003
2014

p53 increases caspase-6 expression and activation in muscle tissue expressing mutant huntingtin
Human molecular genetics
Ehrnhoefer, Dagmar E and Skotte, Niels H and Ladha, Safia and Nguyen, Yen T N and Qiu, Xiaofan and Deng, Yu and Huynh, Khuong T and Engemann, Sabine and Nielsen, Signe M and Becanovic, Kristina and Leavitt, Blair R and Hasholt, Lis and Hayden, Michael R
DOI: 10.1093/hmg/ddt458
2014

Clinical utility gene card for: Huntington's disease
European journal of human genetics : EJHG
Saft, Carsten and Leavitt, Blair R and Epplen, Jörg T
DOI: 10.1038/ejhg.2013.206
2014

Aquatherapy for neurodegenerative disorders
Journal of Huntington's disease
Plecash, Alyson R and Leavitt, Blair R
DOI: 10.3233/jhd-140010
2014

Diagnostic criteria for Huntington's disease based on natural history
Movement disorders : official journal of the Movement Disorder Society
Reilmann, Ralf and Leavitt, Blair R and Ross, Christopher A
DOI: 10.1002/mds.26011
2014

A systematic review and meta-analysis of clinical variables used in Huntington disease research.
Movement disorders : official journal of the Movement Disorder Society
DOI: 10.1002/mds.25663
PubMed: 24142393
10/2013

We are pleased to introduce this next volume of the Journal of Huntington's Disease. Introduction.
Journal of Huntington's disease
DOI: 10.3233/jhd-130003
PubMed: 25057106
01/2013

Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy
Human brain mapping
Scahill, Rachael I and Hobbs, Nicola Z and Say, Miranda J and Bechtel, Natalie and Henley, Susie M D and Hyare, Harpreet and Langbehn, Douglas R and Jones, Rebecca and Leavitt, Blair R and Roos, Raymund A C and Durr, Alexandra and Johnson, Hans and Lehéricy, Stéphane and Craufurd, David and Kennard, Christopher and Hicks, Stephen L and Stout, Julie C and Reilmann, Ralf and Tabrizi, Sarah J and {TRACK-HD investigators}
DOI: 10.1002/hbm.21449
2013

Frontotemporal degeneration, the next therapeutic frontier: molecules and animal models for frontotemporal degeneration drug development
Alzheimer's & dementia : the journal of the Alzheimer's Association
Boxer, Adam L and Gold, Michael and Huey, Edward and Gao, Fen-Biao and Burton, Edward A and Chow, Tiffany and Kao, Aimee and Leavitt, Blair R and Lamb, Bruce and Grether, Megan and Knopman, David and Cairns, Nigel J and Mackenzie, Ian R and Mitic, Laura and Roberson, Erik D and Van Kammen, Daniel and Cantillon, Marc and Zahs, Kathleen and Salloway, Stephen and Morris, John and Tong, Gary and Feldman, Howard and Fillit, Howard and Dickinson, Susan and Khachaturian, Zaven and Sutherland, Margaret and Farese, Robert and Miller, Bruce L and Cummings, Jeffrey
DOI: 10.1016/j.jalz.2012.03.002
2013

The advantages of frontotemporal degeneration drug development (part 2 of frontotemporal degeneration: the next therapeutic frontier)
Alzheimer's & dementia : the journal of the Alzheimer's Association
Boxer, Adam L and Gold, Michael and Huey, Edward and Hu, William T and Rosen, Howard and Kramer, Joel and Gao, Fen-Biao and Burton, Edward A and Chow, Tiffany and Kao, Aimee and Leavitt, Blair R and Lamb, Bruce and Grether, Megan and Knopman, David and Cairns, Nigel J and Mackenzie, Ian R and Mitic, Laura and Roberson, Erik D and Van Kammen, Daniel and Cantillon, Marc and Zahs, Kathleen and Jackson, George and Salloway, Stephen and Morris, John and Tong, Gary and Feldman, Howard and Fillit, Howard and Dickinson, Susan and Khachaturian, Zaven S and Sutherland, Margaret and Abushakra, Susan and Lewcock, Joseph and Farese, Robert and Kenet, Robert O and Laferla, Frank and Perrin, Steve and Whitaker, Steve and Honig, Lawrence and Mesulam, Marsel M and Boeve, Brad and Grossman, Murray and Miller, Bruce L and Cummings, Jeffrey L
DOI: 10.1016/j.jalz.2012.03.003
2013

A randomized, double-blind, placebo-controlled study of latrepirdine in patients with mild to moderate Huntington disease
JAMA neurology
{HORIZON Investigators of the Huntington Study Group and European Huntington's Disease Network}
DOI: 10.1001/2013.jamaneurol.382
2013

Postnatal muscle modification by myogenic factors modulates neuropathology and survival in an ALS mouse model
Nature communications
Park, Kevin H J and Franciosi, Sonia and Leavitt, Blair R
DOI: 10.1038/ncomms3906
2013

Corpus callosal atrophy in premanifest and early Huntington's disease
Journal of Huntington's disease
Crawford, Helen E and Hobbs, Nicola Z and Keogh, Ruth and Langbehn, Douglas R and Frost, Chris and Johnson, Hans and Landwehrmeyer, Bernhard and Reilmann, Ralf and Craufurd, David and Stout, Julie C and Durr, Alexandra and Leavitt, Blair R and Roos, Raymund A C and Tabrizi, Sarah J and Scahill, Rachael I and {TRACK-HD Investigators}'s disease
DOI: 10.3233/jhd-130077
2013

Quality of life in Huntington's disease: a comparative study investigating the impact for those with pre-manifest and early manifest disease, and their partners
Journal of Huntington's disease
Read, Joy and Jones, Rebecca and Owen, Gail and Leavitt, Blair R and Coleman, Allison and Roos, Raymund A C and Dumas, Eve M and Durr, Alexandra and Justo, Damian and Say, Miranda and Stout, Julie C and Tabrizi, Sarah J and Craufurd, David and {TRACK-HD investigators}'s disease
DOI: 10.3233/jhd-130051
2013

8OHdG is not a biomarker for Huntington disease state or progression
Neurology
Borowsky, Beth and Warner, John and Leavitt, Blair R and Tabrizi, Sarah J and Roos, Raymund A C and Durr, Alexandra and Becker, Chris and Sampaio, Cristina and Tobin, Allan J and Schulman, Howard
DOI: 10.1212/wnl.0b013e318293e1a1
2013

Predictors of phenotypic progression and disease onset in premanifest and early-stage Huntington's disease in the TRACK-HD study: analysis of 36-month observational data
The Lancet. Neurology
Tabrizi, Sarah J and Scahill, Rachael I and Owen, Gail and Durr, Alexandra and Leavitt, Blair R and Roos, Raymund A and Borowsky, Beth and Landwehrmeyer, Bernhard and Frost, Chris and Johnson, Hans and Craufurd, David and Reilmann, Ralf and Stout, Julie C and Langbehn, Douglas R and {TRACK-HD Investigators}
DOI: 10.1016/s1474-4422(13)70088-7
2013

Sensitivity to neurotoxic stress is not increased in progranulin-deficient mice
Neurobiology of aging
Petkau, Terri L and Zhu, Shanshan and Lu, Ge and Fernando, Sarah and Cynader, Max and Leavitt, Blair R
DOI: 10.1016/j.neurobiolaging.2013.04.019
2013

Age-dependent alterations of the kynurenine pathway in the YAC128 mouse model of Huntington disease
Journal of neurochemistry
Mazarei, Gelareh and Budac, David P and Lu, Ge and Adomat, Hans and Tomlinson Guns, Emma S and Möller, Thomas and Leavitt, Blair R
DOI: 10.1111/jnc.12350
2013

Progranulin promotes activation of microglia/macrophage after pilocarpine-induced status epilepticus
Brain research
Zhu, Shanshan and Tai, Chao and Petkau, Terri L and Zhang, Si and Liao, Chengyong and Dong, Zhifang and Wen, Wendy and Chang, Qing and Tian Wang, Yu and MacVicar, Brian A and Leavitt, Blair R and Jia, William and Cynader, Max S
DOI: 10.1016/j.brainres.2013.07.023
2013

The absence of indoleamine 2,3-dioxygenase expression protects against NMDA receptor-mediated excitotoxicity in mouse brain
Experimental neurology
Mazarei, G and Budac, DP and Lu, G and Lee, H and Möller, T and Leavitt, BR
DOI: 10.1016/j.expneurol.2013.08.007
2013

8OHdG as a marker for Huntington disease progression.
Neurobiology of disease
DOI: 10.1016/j.nbd.2012.02.012
PubMed: 22414782
03/2012

Decreasing Levels of the cdk5 Activators, p25 and p35, Reduces Excitotoxicity in Striatal Neurons.
Journal of Huntington's disease
DOI: 10.3233/jhd-2012-129000
PubMed: 24353748
01/2012

Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease
Journal of neurology, neurosurgery, and psychiatry
Stout, Julie C and Jones, Rebecca and Labuschagne, Izelle and O'Regan, Alison M and Say, Miranda J and Dumas, Eve M and Queller, Sarah and Justo, Damian and Santos, Rachelle Dar and Coleman, Allison and Hart, Ellen P and Dürr, Alexandra and Leavitt, Blair R and Roos, Raymund A and Langbehn, Doug R and Tabrizi, Sarah J and Frost, Chris
DOI: 10.1136/jnnp-2011-301940
2012

Age-dependent neurovascular abnormalities and altered microglial morphology in the YAC128 mouse model of Huntington disease
Neurobiology of disease
Franciosi, Sonia and Ryu, Jae K and Shim, Yaein and Hill, Austin and Connolly, Colum and Hayden, Michael R and McLarnon, James G and Leavitt, Blair R
DOI: 10.1016/j.nbd.2011.09.003
2012

Synaptic dysfunction in progranulin-deficient mice
Neurobiology of disease
Petkau, Terri L and Neal, Scott J and Milnerwood, Austen and Mew, Ada and Hill, Austin M and Orban, Paul and Gregg, Jenny and Lu, Ge and Feldman, Howard H and Mackenzie, Ian R A and Raymond, Lynn A and Leavitt, Blair R
DOI: 10.1016/j.nbd.2011.10.016
2012

Journal of Huntington's Disease
Journal of Huntington's disease
Leavitt, Blair R and Thompson, Leslie M
DOI: 10.3233/jhd-2012-120001
2012

Visual Working Memory Impairment in Premanifest Gene-Carriers and Early Huntington's Disease
Journal of Huntington's disease
Dumas, Eve M and Say, Miranda J and Jones, Rebecca and Labuschagne, Izelle and O'Regan, Alison M and Hart, Ellen P and van den Bogaard, Simon J A and Queller, Sarah and Justo, Damian and Coleman, Allison and Dar Santos, Rachelle C and Dürr, Alexandra and Leavitt, Blair R and Tabrizi, Sarah J and Roos, Raymund A C and Stout, Julie C
DOI: 10.3233/jhd-2012-120010
2012

Forkhead box protein p1 is a transcriptional repressor of immune signaling in the CNS: implications for transcriptional dysregulation in Huntington disease
Human molecular genetics
Tang, Bin and Becanovic, Kristina and Desplats, Paula A and Spencer, Brian and Hill, Austin M and Connolly, Colum and Masliah, Eliezer and Leavitt, Blair R and Thomas, Elizabeth A
DOI: 10.1093/hmg/dds132
2012

Cystamine and ethyl-eicosapentaenoic acid treatment fail to prevent malonate-induced striatal toxicity in mice.
Neurobiology of aging
DOI: 10.1016/j.neurobiolaging.2011.05.020
PubMed: 21741126
07/2011

Development of biomarkers for Huntington's disease.
The Lancet. Neurology
DOI: 10.1016/s1474-4422(11)70070-9
PubMed: 21601164
06/2011

Biological and clinical changes in premanifest and early stage Huntington's disease in the TRACK-HD study: the 12-month longitudinal analysis
The Lancet. Neurology
Tabrizi, Sarah J and Scahill, Rachael I and Durr, Alexandra and Roos, Raymund Ac and Leavitt, Blair R and Jones, Rebecca and Landwehrmeyer, G Bernhard and Fox, Nick C and Johnson, Hans and Hicks, Stephen L and Kennard, Christopher and Craufurd, David and Frost, Chris and Langbehn, Douglas R and Reilmann, Ralf and Stout, Julie C and {TRACK-HD Investigators}
DOI: 10.1016/s1474-4422(10)70276-3
2011

The structural involvement of the cingulate cortex in premanifest and early Huntington's disease
Movement disorders : official journal of the Movement Disorder Society
Hobbs, Nicola Z and Pedrick, Amy V and Say, Miranda J and Frost, Chris and Dar Santos, Rachelle and Coleman, Allison and Sturrock, Aaron and Craufurd, David and Stout, Julie C and Leavitt, Blair R and Barnes, Josephine and Tabrizi, Sarah J and Scahill, Rachael I
DOI: 10.1002/mds.23747
2011

YB-1 bridges neural stem cells and brain tumor-initiating cells via its roles in differentiation and cell growth
Cancer research
Fotovati, Abbas and Abu-Ali, Samah and Wang, Pei-Shan and Deleyrolle, Loic P and Lee, Cathy and Triscott, Joanna and Chen, James Y and Franciosi, Sonia and Nakamura, Yasuhiro and Sugita, Yasuo and Uchiumi, Takeshi and Kuwano, Michihiko and Leavitt, Blair R and Singh, Sheila K and Jury, Alexa and Jones, Chris and Wakimoto, Hiroaki and Reynolds, Brent A and Pallen, Catherine J and Dunn, Sandra E
DOI: 10.1158/0008-5472.can-10-2805
2011

Magnetic resonance spectroscopy biomarkers in premanifest and early Huntington disease.
Neurology
DOI: 10.1212/wnl.0b013e3181fc27e4
PubMed: 21060093
11/2010

Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression
Human molecular genetics
Pouladi, Mahmoud A and Xie, Yuanyun and Skotte, Niels Henning and Ehrnhoefer, Dagmar E and Graham, Rona K and Kim, Jeong Eun and Bissada, Nagat and Yang, X William and Paganetti, Paolo and Friedlander, Robert M and Leavitt, Blair R and Hayden, Michael R
DOI: 10.1093/hmg/ddq026
2010

Progranulin expression in the developing and adult murine brain
The Journal of comparative neurology
Petkau, Terri L and Neal, SJ and Orban, PC and MacDonald, JL and Hill, AM and Lu, G and Feldman, HH and Mackenzie, I R A and Leavitt, BR
DOI: 10.1002/cne.22430
2010

Phosphorylation of huntingtin at Ser421 in YAC128 neurons is associated with protection of YAC128 neurons from NMDA-mediated excitotoxicity and is modulated by PP1 and PP2A
The Journal of neuroscience : the official journal of the Society for Neuroscience
Metzler, Martina and Gan, Lu and Mazarei, Gelareh and Graham, Rona K and Liu, Lili and Bissada, Nagat and Lu, Ge and Leavitt, Blair R and Hayden, Michael R
DOI: 10.1523/jneurosci.1589-10.2010
2010

The clinical and genetic features of Huntington disease
Journal of geriatric psychiatry and neurology
Sturrock, Aaron and Leavitt, Blair R
DOI: 10.1177/0891988710383573
2010

Tapping linked to function and structure in premanifest and symptomatic Huntington disease
Neurology
Bechtel, N and Scahill, RI and Rosas, HD and Acharya, T and van den Bogaard, S J A and Jauffret, C and Say, MJ and Sturrock, A and Johnson, H and Onorato, CE and Salat, DH and Durr, A and Leavitt, BR and Roos, R A C and Landwehrmeyer, GB and Langbehn, DR and Stout, JC and Tabrizi, SJ and Reilmann, R
DOI: 10.1212/wnl.0b013e3182020123
2010

Expression analysis of novel striatal-enriched genes in Huntington disease
Human molecular genetics
Mazarei, Gelareh and Neal, Scott J and Becanovic, Kristina and Luthi-Carter, Ruth and Simpson, Elizabeth M and Leavitt, Blair R
DOI: 10.1093/hmg/ddp527
2010

Transcriptional changes in Huntington disease identified using genome-wide expression profiling and cross-platform analysis
Human molecular genetics
Becanovic, Kristina and Pouladi, Mahmoud A and Lim, Raymond S and Kuhn, Alexandre and Pavlidis, Paul and Luthi-Carter, Ruth and Hayden, Michael R and Leavitt, Blair R
DOI: 10.1093/hmg/ddq018
2010

Tetrabenazine.
Nature reviews. Drug discovery
DOI: 10.1038/nrd2784
PubMed: 19116624
01/2009

Biological and clinical manifestations of Huntington's disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data
The Lancet. Neurology
Tabrizi, Sarah J and Langbehn, Douglas R and Leavitt, Blair R and Roos, Raymund Ac and Durr, Alexandra and Craufurd, David and Kennard, Christopher and Hicks, Stephen L and Fox, Nick C and Scahill, Rachael I and Borowsky, Beth and Tobin, Allan J and Rosas, H Diana and Johnson, Hans and Reilmann, Ralf and Landwehrmeyer, Bernhard and Stout, Julie C and {TRACK-HD investigators}
DOI: 10.1016/s1474-4422(09)70170-x
2009

Gender differences in expression of the human caspase-12 long variant determines susceptibility to Listeria monocytogenes infection
Proceedings of the National Academy of Sciences of the United States of America
Yeretssian, Garabet and Doiron, Karine and Shao, Wei and Leavitt, Blair R and Hayden, Michael R and Nicholson, Donald W and Saleh, Maya
DOI: 10.1073/pnas.0813362106
2009

Age-dependent alterations of corticostriatal activity in the YAC128 mouse model of Huntington disease
The Journal of neuroscience : the official journal of the Society for Neuroscience
Joshi, Prasad R and Wu, Nan-Ping and André, Véronique M and Cummings, Damian M and Cepeda, Carlos and Joyce, John A and Carroll, Jeffrey B and Leavitt, Blair R and Hayden, Michael R and Levine, Michael S and Bamford, Nigel S
DOI: 10.1523/jneurosci.5687-08.2009
2009

Differential susceptibility to excitotoxic stress in YAC128 mouse models of Huntington disease between initiation and progression of disease
The Journal of neuroscience : the official journal of the Society for Neuroscience
Graham, Rona K and Pouladi, Mahmoud A and Joshi, Prasad and Lu, Ge and Deng, Yu and Wu, Nan-Ping and Figueroa, Bryan E and Metzler, Martina and André, Véronique M and Slow, Elizabeth J and Raymond, Lynn and Friedlander, Robert and Levine, Michael S and Leavitt, Blair R and Hayden, Michael R
DOI: 10.1523/jneurosci.5473-08.2009
2009

Brain-specific proteins decline in the cerebrospinal fluid of humans with Huntington disease
Molecular & cellular proteomics : MCP
Fang, Qiaojun and Strand, Andrew and Law, Wendy and Faca, Vitor M and Fitzgibbon, Matthew P and Hamel, Nathalie and Houle, Benoit and Liu, Xin and May, Damon H and Poschmann, Gereon and Roy, Line and Stühler, Kai and Ying, Wantao and Zhang, Jiyang and Zheng, Zhaobin and Bergeron, John J M and Hanash, Sam and He, Fuchu and Leavitt, Blair R and Meyer, Helmut E and Qian, Xiaohong and McIntosh, Martin W
DOI: 10.1074/mcp.m800231-mcp200
2009

A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease.
The Journal of experimental medicine
DOI: 10.1084/jem.20080178
PubMed: 18625748
07/2008

Re: Autopsy-proven Huntington's disease with 29 trinucleotide repeats
Movement disorders : official journal of the Movement Disorder Society
Semaka, Alicia and Warby, Simon and Leavitt, Blair R and Hayden, Michael R
DOI: 10.1002/mds.21820
2008

Cocaine- and amphetamine-regulated transcript is increased in Huntington disease.
Movement disorders : official journal of the Movement Disorder Society
DOI: 10.1002/mds.21447
PubMed: 17722045
10/2007

Proteomic profiling of plasma in Huntington's disease reveals neuroinflammatory activation and biomarker candidates.
Journal of proteome research
DOI: 10.1021/pr0700753
PubMed: 17552550
06/2007

Chapter 15 Juvenile amyotrophic lateral sclerosis.
Handbook of clinical neurology
DOI: 10.1016/s0072-9752(07)80018-2
PubMed: 18808900
01/2007

CAG-encoded polyglutamine length polymorphism in the human genome
BMC genomics
Butland, Stefanie L and Devon, Rebecca S and Huang, Yong and Mead, Carri-Lyn and Meynert, Alison M and Neal, Scott J and Lee, Soo Sen and Wilkinson, Anna and Yang, George S and Yuen, Macaire M S and Hayden, Michael R and Holt, Robert A and Leavitt, Blair R and Ouellette, B F Francis
DOI: 10.1186/1471-2164-8-126
2007

Ataxia and the role of antigliadin antibodies
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques
Wong, D and Dwinnel, M and Schulzer, M and Nimmo, M and Leavitt, BR and Spacey, SD
DOI: 10.1017/s031716710000603x
2007

Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage
Human molecular genetics
Kuhn, Alexandre and Goldstein, Darlene R and Hodges, Angela and Strand, Andrew D and Sengstag, Thierry and Kooperberg, Charles and Becanovic, Kristina and Pouladi, Mahmoud A and Sathasivam, Kirupa and Cha, Jang-Ho J and Hannan, Anthony J and Hayden, Michael R and Leavitt, Blair R and Dunnett, Stephen B and Ferrante, Robert J and Albin, Roger and Shelbourne, Peggy and Delorenzi, Mauro and Augood, Sarah J and Faull, Richard L M and Olson, James M and Bates, Gillian P and Jones, Lesley and Luthi-Carter, Ruth
DOI: 10.1093/hmg/ddm133
2007

Testicular degeneration in Huntington disease
Neurobiology of disease
Van Raamsdonk, Jeremy M and Murphy, Zoe and Selva, David M and Hamidizadeh, Reza and Pearson, Jacqueline and Petersén, Asa and Björkqvist, Maria and Muir, Cameron and Mackenzie, Ian R and Hammond, Geoffrey L and Vogl, A Wayne and Hayden, Michael R and Leavitt, Blair R
DOI: 10.1016/j.nbd.2007.01.006
2007

Phenotypic abnormalities in the YAC128 mouse model of Huntington disease are penetrant on multiple genetic backgrounds and modulated by strain
Neurobiology of disease
Van Raamsdonk, Jeremy M and Metzler, Martina and Slow, Elizabeth and Pearson, Jacqueline and Schwab, Claudia and Carroll, Jeffrey and Graham, Rona K and Leavitt, Blair R and Hayden, Michael R
DOI: 10.1016/j.nbd.2006.12.010
2007

Als2-deficient mice exhibit disturbances in endosome trafficking associated with motor behavioral abnormalities.
Proceedings of the National Academy of Sciences of the United States of America
DOI: 10.1073/pnas.0510197103
PubMed: 16769894
06/2006

Elevated brain 3-hydroxykynurenine and quinolinate levels in Huntington disease mice.
Neurobiology of disease
DOI: 10.1016/j.nbd.2006.02.011
PubMed: 16697652
05/2006

Wild-type huntingtin protects neurons from excitotoxicity.
Journal of neurochemistry
DOI: 10.1111/j.1471-4159.2005.03605.x
PubMed: 16417581
01/2006

Wild-type huntingtin ameliorates striatal neuronal atrophy but does not prevent other abnormalities in the YAC128 mouse model of Huntington disease
BMC neuroscience
Van Raamsdonk, Jeremy M and Pearson, Jacqueline and Murphy, Zoe and Hayden, Michael R and Leavitt, Blair R
DOI: 10.1186/1471-2202-7-80
2006

Striatal neuronal apoptosis is preferentially enhanced by NMDA receptor activation in YAC transgenic mouse model of Huntington disease
Neurobiology of disease
Shehadeh, Jacqueline and Fernandes, Herman B and Zeron Mullins, Melinda M and Graham, Rona K and Leavitt, Blair R and Hayden, Michael R and Raymond, Lynn A
DOI: 10.1016/j.nbd.2005.08.001
2006

Levels of mutant huntingtin influence the phenotypic severity of Huntington disease in YAC128 mouse models
Neurobiology of disease
Graham, Rona K and Slow, Elizabeth J and Deng, Yu and Bissada, Nagat and Lu, Ge and Pearson, Jacqueline and Shehadeh, Jacqueline and Leavitt, Blair R and Raymond, Lynn A and Hayden, Michael R
DOI: 10.1016/j.nbd.2005.08.007
2006

Huntingtin inhibits caspase-3 activation
The EMBO journal
Zhang, Yu and Leavitt, Blair R and van Raamsdonk, Jeremy M and Dragatsis, Ioannis and Goldowitz, Dan and MacDonald, Marcy E and Hayden, Michael R and Friedlander, Robert M
DOI: 10.1038/sj.emboj.7601445
2006

Familial frontotemporal dementia with neuronal intranuclear inclusions is not a polyglutamine expansion disease
BMC neurology
Mackenzie, Ian R and Butland, Stefanie L and Devon, Rebecca S and Dwosh, Emily and Feldman, Howard and Lindholm, Caroline and Neal, Scott J and Ouellette, B F Francis and Leavitt, Blair R
DOI: 10.1186/1471-2377-6-32
2006

Is tetrabenazine safe and effective for suppressing chorea in Huntington's disease?
Nature clinical practice. Neurology
Leavitt, Blair R and Hayden, Michael R
DOI: 10.1038/ncpneuro0299
2006

Cerebrospinal fluid levels of orexin-A are not a clinically useful biomarker for Huntington disease
Clinical genetics
Björkqvist, M and Petersén, A and Nielsen, J and Ecker, D and Mulder, H and Hayden, MR and Landwehrmeyer, B and Brundin, P and Leavitt, BR
DOI: 10.1111/j.1399-0004.2006.00636.x
2006

Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin
Cell
Graham, Rona K and Deng, Yu and Slow, Elizabeth J and Haigh, Brendan and Bissada, Nagat and Lu, Ge and Pearson, Jacqueline and Shehadeh, Jacqueline and Bertram, Lisa and Murphy, Zoe and Warby, Simon C and Doty, Crystal N and Roy, Sophie and Wellington, Cheryl L and Leavitt, Blair R and Raymond, Lynn A and Nicholson, Donald W and Hayden, Michael R
DOI: 10.1016/j.cell.2006.04.026
2006

Body weight is modulated by levels of full-length huntingtin
Human molecular genetics
Van Raamsdonk, Jeremy M and Gibson, William T and Pearson, Jacqueline and Murphy, Zoe and Lu, Ge and Leavitt, Blair R and Hayden, Michael R
DOI: 10.1093/hmg/ddl072
2006

Selective degeneration and nuclear localization of mutant huntingtin in the YAC128 mouse model of Huntington disease
Human molecular genetics
Van Raamsdonk, Jeremy M and Murphy, Zoe and Slow, Elizabeth J and Leavitt, Blair R and Hayden, Michael R
DOI: 10.1093/hmg/ddi407
2005

Cystamine treatment is neuroprotective in the YAC128 mouse model of Huntington disease
Journal of neurochemistry
Van Raamsdonk, Jeremy M and Pearson, Jacqueline and Bailey, Craig D C and Rogers, Daniel A and Johnson, Gail V W and Hayden, Michael R and Leavitt, Blair R
DOI: 10.1111/j.1471-4159.2005.03357.x
2005

Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions
Proceedings of the National Academy of Sciences of the United States of America
Slow, Elizabeth J and Graham, Rona K and Osmand, Alexander P and Devon, Rebecca S and Lu, Ge and Deng, Yu and Pearson, Jacqui and Vaid, Kuljeet and Bissada, Nagat and Wetzel, Ronald and Leavitt, Blair R and Hayden, Michael R
DOI: 10.1073/pnas.0503634102
2005

Ethyl-EPA treatment improves motor dysfunction, but not neurodegeneration in the YAC128 mouse model of Huntington disease
Experimental neurology
Van Raamsdonk, Jeremy M and Pearson, Jacqueline and Rogers, Daniel A and Lu, Ge and Barakauskas, Vilte E and Barr, Alasdair M and Honer, William G and Hayden, Michael R and Leavitt, Blair R
DOI: 10.1016/j.expneurol.2005.07.021
2005

Ethyl-EPA in Huntington disease: a double-blind, randomized, placebo-controlled trial
Neurology
Puri, BK and Leavitt, BR and Hayden, MR and Ross, CA and Rosenblatt, A and Greenamyre, JT and Hersch, S and Vaddadi, KS and Sword, A and Horrobin, DF and Manku, M and Murck, H
DOI: 10.1212/01.wnl.0000169025.09670.6d
2005

Treatment of YAC128 mice and their wild-type littermates with cystamine does not lead to its accumulation in plasma or brain: implications for the treatment of Huntington disease
Journal of neurochemistry
Pinto, John T and Van Raamsdonk, Jeremy M and Leavitt, Blair R and Hayden, Michael R and Jeitner, Thomas M and Thaler, Howard T and Krasnikov, Boris F and Cooper, Arthur J L
DOI: 10.1111/j.1471-4159.2005.03255.x
2005

Satellog: a database for the identification and prioritization of satellite repeats in disease association studies
BMC bioinformatics
Missirlis, Perseus I and Mead, Carri-Lyn R and Butland, Stefanie L and Ouellette, B F Francis and Devon, Rebecca S and Leavitt, Blair R and Holt, Robert A
DOI: 10.1186/1471-2105-6-145
2005

Loss of wild-type huntingtin influences motor dysfunction and survival in the YAC128 mouse model of Huntington disease
Human molecular genetics
Van Raamsdonk, Jeremy M and Pearson, Jacqueline and Rogers, Daniel A and Bissada, Nagat and Vogl, A Wayne and Hayden, Michael R and Leavitt, Blair R
DOI: 10.1093/hmg/ddi147
2005

Cognitive dysfunction precedes neuropathology and motor abnormalities in the YAC128 mouse model of Huntington's disease
The Journal of neuroscience : the official journal of the Society for Neuroscience
Van Raamsdonk, Jeremy M and Pearson, Jacqueline and Slow, Elizabeth J and Hossain, Sazzad M and Leavitt, Blair R and Hayden, Michael R
DOI: 10.1523/jneurosci.0590-05.2005
2005

Cross-species characterization of the ALS2 gene and analysis of its pattern of expression in development and adulthood
Neurobiology of disease
Devon, Rebecca S and Schwab, Claudia and Topp, Justin D and Orban, Paul C and Yang, Yu-Zhou and Pape, Terry D and Helm, Jeffrey R and Davidson, Tara-Lynne and Rogers, Daniel A and Gros-Louis, Francois and Rouleau, Guy and Horazdovsky, Bruce F and Leavitt, Blair R and Hayden, Michael R
DOI: 10.1016/j.nbd.2004.10.002
2005

Potentiation of NMDA receptor-mediated excitotoxicity linked with intrinsic apoptotic pathway in YAC transgenic mouse model of Huntington's disease.
Molecular and cellular neurosciences
DOI: 10.1016/j.mcn.2003.11.014
PubMed: 15033175
03/2004

Novel ventriculo-peritoneal shunt in Alzheimer's disease cerebrospinal fluid biomarkers.
Expert review of neurotherapeutics
DOI: 10.1586/14737175.4.1.97
PubMed: 15853620
01/2004

Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington's disease.
Human molecular genetics
DOI: 10.1093/hmg/11.17.1939
PubMed: 12165556
08/2002

Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease.
Science (New York, N.Y.)
DOI: 10.1126/science.1059581
PubMed: 11408619
06/2001

A one-hit model of cell death in inherited neuronal degenerations.
Nature
DOI: 10.1038/35018098
PubMed: 10910361
07/2000

Huntington disease: new insights on the role of huntingtin cleavage.
Journal of neural transmission. Supplementum
DOI: 10.1007/978-3-7091-6284-2_1
PubMed: 11128600
01/2000

Differentiation of transplanted neural precursors varies regionally in adults striatum.
Neuroreport
DOI: 10.1097/00001756-199912160-00045
PubMed: 10716243
12/1999

A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration.
Neuron
DOI: 10.1016/s0896-6273(00)80764-3
PubMed: 10402204
05/1999

Research

Current Projects
I’ve recently established The Laboratory for Experimental Therapeutics in Animal Models of Human Disease at the Centre for Molecular Medicine and Therapeutics (CMMT), dedicated to developing new treatments for hereditary brain diseases, such as Huntington’s disease, Fragile X, and Lou Gehrig’s disease. Molecular genetic tools are used to generate transgenic animal models of these diseases. New approaches to treatment are then tested in these models, with the goal of accelerating the progress of new treatments from the bench to the clinic. This facility’s resources and expertise provide the basis for collaborative projects with scientists worldwide.

My laboratory includes a mouse behavioural testing unit allowing phenotypic characterization of large numbers of transgenic mice using a standardized behavioural protocol, as well as a dedicated small animal surgical suite allowing a variety of surgical procedures including administration of stem cells, compounds or gene therapy vectors directly into the CNS. I’ve established a dedicated image analysis suite, stereology system, and automated neuropathology unit for high-throughput quantitative analysis of neurodegeneration in transgenic mouse brains. We currently have an established level II biohazard protocol, and are performing gene therapy experiments using adenoviral and adeno-associated viral vectors. I also have several ongoing projects investigating the role of wild-type huntingtin in neuronal apoptosis and a possible role for loss of huntingtin function in neurodegenerative disease.

The primary mouse model used in my laboratory is a Yeast Artificial chromosome (YAC) transgenic mouse model of Huntington’s Disease (HD) originally developed in Michael Hayden's laboratory at the CMMT. This mouse model faithfully replicates key features of the human disease; specifically these mice develop age-related motor dysfunction, behavioural abnormalities, and selective neurodegeneration of medium spiny neurons of the striatum. YAC transgenic mice have now been generated with the full-length human HD gene containing normal (YAC18) and expanded (YAC46, 72, and 128) CAG repeats. Different lines of transgenic mice have varying copy numbers of the human transgene and express varying amounts of transgenic huntingtin protein. The progressive motor and neurodegenerative phenotype of the YAC128 mouse model of HD makes in vivo screening of novel therapeutic approaches viable.

Several trials of potential therapeutic agents have now been initiated in our YAC transgenic mouse model. Novel therapeutic approaches effective in our HD model will likely have utility in a broad range of neurodegenerative disorders, and in the future we’ll utilize the same approach to investigate new therapeutics in other neurodegenerative disorders, such as ALS, Parkinson’s disease, and Alzheimer’s disease.

In addition, I’m a neurologist with an ongoing clinical practice and clinical research program in neurogenetics, with a focus on hereditary movement disorders, specifically various forms of ataxia and chorea. I’m involved in post-mortem studies of HD patients as well as clinical research directed at identifying novel forms of CAG repeat disorders. I’m involved in clinical trials of new therapeutics in Huntington’s disease and other hereditary neurologic disorders such as the spinocerebellar ataxias and Friedrich’s Ataxia. I’m also the Director of the Canadian Genetic Disease Network Transgenic Core Facility at the CMMT, which generates transgenic and gene-targeted mice as models of human disease for investigators from across North America.

Honours & Awards

Young Investigator Award, Brain Research Centre, University of British Columbia, 1999

Award for Outstanding Achievement by a Postdoctoral Fellow, BC Research Institute for Children’s & Women’s Health, 2001

Michael Smith Foundation for Health Research Career Investigator Award, 2007

Research Group Members

Muna Abedrabbo, Master's Student
Hilal Al Shekaili, Dr
Laura Chan, Medical Genetics Graduate Program Rotation Student
Angela Gurney, Research Coordinator
Pardis Kazemian, Trainee
Ben Life, Doctoral Student
Kayla Shayne, Manager Transgenic Facility
Sarah Thomson, Graduate Student