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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Huntingtin suppression restores cognitive function in a mouse model of Huntington's disease. / Southwell, Amber L; Kordasiewicz, Holly B; Langbehn, Douglas; Skotte, Niels H.; Parsons, Matthew P; Villanueva, Erika B; Caron, Nicholas S; Østergaard, Michael E; Anderson, Lisa M; Xie, Yuanyun; Cengio, Louisa Dal; Findlay-Black, Hailey; Doty, Crystal N; Fitsimmons, Bethany; Swayze, Eric E; Seth, Punit P; Raymond, Lynn A; Frank Bennett, C; Hayden, Michael R.

In: Science Translational Medicine, Vol. 10, No. 461, eaar3959, 2018, p. 1-12.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Southwell, AL, Kordasiewicz, HB, Langbehn, D, Skotte, NH, Parsons, MP, Villanueva, EB, Caron, NS, Østergaard, ME, Anderson, LM, Xie, Y, Cengio, LD, Findlay-Black, H, Doty, CN, Fitsimmons, B, Swayze, EE, Seth, PP, Raymond, LA, Frank Bennett, C & Hayden, MR 2018, 'Huntingtin suppression restores cognitive function in a mouse model of Huntington's disease', Science Translational Medicine, vol. 10, no. 461, eaar3959, pp. 1-12. https://doi.org/10.1126/scitranslmed.aar3959

APA

Southwell, A. L., Kordasiewicz, H. B., Langbehn, D., Skotte, N. H., Parsons, M. P., Villanueva, E. B., Caron, N. S., Østergaard, M. E., Anderson, L. M., Xie, Y., Cengio, L. D., Findlay-Black, H., Doty, C. N., Fitsimmons, B., Swayze, E. E., Seth, P. P., Raymond, L. A., Frank Bennett, C., & Hayden, M. R. (2018). Huntingtin suppression restores cognitive function in a mouse model of Huntington's disease. Science Translational Medicine, 10(461), 1-12. [eaar3959]. https://doi.org/10.1126/scitranslmed.aar3959

Vancouver

Southwell AL, Kordasiewicz HB, Langbehn D, Skotte NH, Parsons MP, Villanueva EB et al. Huntingtin suppression restores cognitive function in a mouse model of Huntington's disease. Science Translational Medicine. 2018;10(461):1-12. eaar3959. https://doi.org/10.1126/scitranslmed.aar3959

Author

Southwell, Amber L ; Kordasiewicz, Holly B ; Langbehn, Douglas ; Skotte, Niels H. ; Parsons, Matthew P ; Villanueva, Erika B ; Caron, Nicholas S ; Østergaard, Michael E ; Anderson, Lisa M ; Xie, Yuanyun ; Cengio, Louisa Dal ; Findlay-Black, Hailey ; Doty, Crystal N ; Fitsimmons, Bethany ; Swayze, Eric E ; Seth, Punit P ; Raymond, Lynn A ; Frank Bennett, C ; Hayden, Michael R. / Huntingtin suppression restores cognitive function in a mouse model of Huntington's disease. In: Science Translational Medicine. 2018 ; Vol. 10, No. 461. pp. 1-12.

Bibtex

@article{31428ce6c71c47ad824eaad310cac31a,
title = "Huntingtin suppression restores cognitive function in a mouse model of Huntington's disease",
abstract = "Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a mutation in the huntingtin (HTT) protein, resulting in acquisition of toxic functions. Previous studies have shown that lowering mutant HTT has the potential to be broadly beneficial. We previously identified HTT single-nucleotide polymorphisms (SNPs) tightly linked to the HD mutation and developed antisense oligonucleotides (ASOs) targeting HD-SNPs that selectively suppress mutant HTT. We tested allele-specific ASOs in a mouse model of HD. Both early and late treatment reduced cognitive and behavioral impairments in mice. To determine the translational potential of the treatment, we examined the effect of ASO administration on HTT brain expression in nonhuman primates. The treatment induced robust HTT suppression throughout the cortex and limbic system, areas implicated in cognition and psychiatric function. The results suggest that ASOs specifically targeting mutated HTT might have therapeutic effects on HD-mediated cognitive impairments.",
author = "Southwell, {Amber L} and Kordasiewicz, {Holly B} and Douglas Langbehn and Skotte, {Niels H.} and Parsons, {Matthew P} and Villanueva, {Erika B} and Caron, {Nicholas S} and {\O}stergaard, {Michael E} and Anderson, {Lisa M} and Yuanyun Xie and Cengio, {Louisa Dal} and Hailey Findlay-Black and Doty, {Crystal N} and Bethany Fitsimmons and Swayze, {Eric E} and Seth, {Punit P} and Raymond, {Lynn A} and {Frank Bennett}, C and Hayden, {Michael R}",
note = "Niels H. Skotte : Present address: Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark. Erika B Villanueva : Present address: Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen 2200, Denmark.",
year = "2018",
doi = "10.1126/scitranslmed.aar3959",
language = "English",
volume = "10",
pages = "1--12",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "american association for the advancement of science",
number = "461",

}

RIS

TY - JOUR

T1 - Huntingtin suppression restores cognitive function in a mouse model of Huntington's disease

AU - Southwell, Amber L

AU - Kordasiewicz, Holly B

AU - Langbehn, Douglas

AU - Skotte, Niels H.

AU - Parsons, Matthew P

AU - Villanueva, Erika B

AU - Caron, Nicholas S

AU - Østergaard, Michael E

AU - Anderson, Lisa M

AU - Xie, Yuanyun

AU - Cengio, Louisa Dal

AU - Findlay-Black, Hailey

AU - Doty, Crystal N

AU - Fitsimmons, Bethany

AU - Swayze, Eric E

AU - Seth, Punit P

AU - Raymond, Lynn A

AU - Frank Bennett, C

AU - Hayden, Michael R

N1 - Niels H. Skotte : Present address: Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark. Erika B Villanueva : Present address: Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen 2200, Denmark.

PY - 2018

Y1 - 2018

N2 - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a mutation in the huntingtin (HTT) protein, resulting in acquisition of toxic functions. Previous studies have shown that lowering mutant HTT has the potential to be broadly beneficial. We previously identified HTT single-nucleotide polymorphisms (SNPs) tightly linked to the HD mutation and developed antisense oligonucleotides (ASOs) targeting HD-SNPs that selectively suppress mutant HTT. We tested allele-specific ASOs in a mouse model of HD. Both early and late treatment reduced cognitive and behavioral impairments in mice. To determine the translational potential of the treatment, we examined the effect of ASO administration on HTT brain expression in nonhuman primates. The treatment induced robust HTT suppression throughout the cortex and limbic system, areas implicated in cognition and psychiatric function. The results suggest that ASOs specifically targeting mutated HTT might have therapeutic effects on HD-mediated cognitive impairments.

AB - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a mutation in the huntingtin (HTT) protein, resulting in acquisition of toxic functions. Previous studies have shown that lowering mutant HTT has the potential to be broadly beneficial. We previously identified HTT single-nucleotide polymorphisms (SNPs) tightly linked to the HD mutation and developed antisense oligonucleotides (ASOs) targeting HD-SNPs that selectively suppress mutant HTT. We tested allele-specific ASOs in a mouse model of HD. Both early and late treatment reduced cognitive and behavioral impairments in mice. To determine the translational potential of the treatment, we examined the effect of ASO administration on HTT brain expression in nonhuman primates. The treatment induced robust HTT suppression throughout the cortex and limbic system, areas implicated in cognition and psychiatric function. The results suggest that ASOs specifically targeting mutated HTT might have therapeutic effects on HD-mediated cognitive impairments.

U2 - 10.1126/scitranslmed.aar3959

DO - 10.1126/scitranslmed.aar3959

M3 - Journal article

C2 - 30282695

VL - 10

SP - 1

EP - 12

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 461

M1 - eaar3959

ER -

ID: 209264809