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Toward allele-speci...
Toward allele-specific targeting therapy and pharmacodynamic marker for spinocerebellar ataxia type 3
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- Prudencio, Mercedes (author)
- Mayo Clinic Florida
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Garcia-Moreno, Hector (author)
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- Jansen-West, Karen R (author)
- University of Geneva
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- Al-Shaikh, Rana Hanna (author)
- Nordsjællands Hospital
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- Gendron, Tania F (author)
- University of Geneva
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- Heckman, Michael G (author)
- Mayo Clinic Minnesota
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- Spiegel, Matthew R (author)
- Mayo Clinic Minnesota
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- Carlomagno, Yari (author)
- University of Geneva
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- Daughrity, Lillian M (author)
- University of Geneva
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- Song, Yuping (author)
- University of Geneva
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- Dunmore, Judith A (author)
- University of Geneva
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- Byron, Natalie (author)
- University of Geneva
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- Oskarsson, Björn (author)
- Nordsjællands Hospital
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Nicholson, Katharine A (author)
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- Staff, Nathan P (author)
- Nordsjællands Hospital
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- Gorcenco, Sorina (author)
- Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Puschmann, Andreas (author)
- Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Lemos, João (author)
- Center for Neuroscience and Cell Biology, University of Coimbra
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- Januário, Cristina (author)
- Center for Neuroscience and Cell Biology, University of Coimbra
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LeDoux, Mark S (author)
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Friedman, Joseph H (author)
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Polke, James (author)
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Labrum, Robin (author)
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- Shakkottai, Vikram (author)
- Western Michigan University
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- McLoughlin, Hayley S (author)
- Western Michigan University
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- Paulson, Henry L (author)
- Western Michigan University
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- Konno, Takuya (author)
- Niigata University
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- Onodera, Osamu (author)
- Niigata University
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- Ikeuchi, Takeshi (author)
- Niigata University
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- Tada, Mari (author)
- Niigata University
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- Kakita, Akiyoshi (author)
- Niigata University
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Fryer, John D (author)
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- Karremo, Christin (author)
- Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Gomes, Inês (author)
- Center for Neuroscience and Cell Biology, University of Coimbra
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- Caviness, John N (author)
- Nordsjællands Hospital
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Pittelkow, Mark R (author)
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- Aasly, Jan (author)
- Norwegian University of Science and Technology
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- Pfeiffer, Ronald F (author)
- Oregon Health & Science University
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- Veerappan, Venka (author)
- Oregon Health & Science University
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- Eggenberger, Eric R (author)
- Nordsjællands Hospital
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- Freeman, William D (author)
- Nordsjællands Hospital
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- Huang, Josephine F (author)
- Nordsjællands Hospital
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- Uitti, Ryan J (author)
- Nordsjællands Hospital
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- Wierenga, Klaas J (author)
- Nordsjællands Hospital
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- Marin Collazo, Iris V (author)
- Nordsjællands Hospital
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- Tipton, Philip W (author)
- Nordsjællands Hospital
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- van Gerpen, Jay A (author)
- University of South Alabama
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- van Blitterswijk, Marka (author)
- University of Geneva
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- Bu, Guojun (author)
- University of Geneva
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- Wszolek, Zbigniew K (author)
- Nordsjællands Hospital
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- Petrucelli, Leonard (author)
- Mayo Clinic Florida
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(creator_code:org_t)
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et al
- American Association for the Advancement of Science (AAAS), 2020
- 2020
- English.
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In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 12:566
- Related links:
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http://dx.doi.org/10...
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https://www.ncbi.nlm...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Spinocerebellar ataxia type 3 (SCA3), caused by a CAG repeat expansion in the ataxin-3 gene (ATXN3), is characterized by neuronal polyglutamine (polyQ) ATXN3 protein aggregates. Although there is no cure for SCA3, gene-silencing approaches to reduce toxic polyQ ATXN3 showed promise in preclinical models. However, a major limitation in translating putative treatments for this rare disease to the clinic is the lack of pharmacodynamic markers for use in clinical trials. Here, we developed an immunoassay that readily detects polyQ ATXN3 proteins in human biological fluids and discriminates patients with SCA3 from healthy controls and individuals with other ataxias. We show that polyQ ATXN3 serves as a marker of target engagement in human fibroblasts, which may bode well for its use in clinical trials. Last, we identified a single-nucleotide polymorphism that strongly associates with the expanded allele, thus providing an exciting drug target to abrogate detrimental events initiated by mutant ATXN3. Gene-silencing strategies for several repeat diseases are well under way, and our results are expected to improve clinical trial preparedness for SCA3 therapies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Prudencio, Merce ...
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Garcia-Moreno, H ...
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Jansen-West, Kar ...
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Al-Shaikh, Rana ...
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Gendron, Tania F
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Heckman, Michael ...
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show more...
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Spiegel, Matthew ...
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Carlomagno, Yari
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Daughrity, Lilli ...
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Song, Yuping
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Dunmore, Judith ...
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Byron, Natalie
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Oskarsson, Björn
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Nicholson, Katha ...
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Staff, Nathan P
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Gorcenco, Sorina
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Puschmann, Andre ...
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Lemos, João
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Januário, Cristi ...
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LeDoux, Mark S
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Friedman, Joseph ...
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Polke, James
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Labrum, Robin
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Shakkottai, Vikr ...
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McLoughlin, Hayl ...
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Paulson, Henry L
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Konno, Takuya
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Onodera, Osamu
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Ikeuchi, Takeshi
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Tada, Mari
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Kakita, Akiyoshi
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Fryer, John D
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Karremo, Christi ...
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Gomes, Inês
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Caviness, John N
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Pittelkow, Mark ...
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Aasly, Jan
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Pfeiffer, Ronald ...
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Veerappan, Venka
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Eggenberger, Eri ...
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Freeman, William ...
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Huang, Josephine ...
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Uitti, Ryan J
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Wierenga, Klaas ...
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Marin Collazo, I ...
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Tipton, Philip W
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van Gerpen, Jay ...
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van Blitterswijk ...
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Bu, Guojun
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Wszolek, Zbignie ...
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Petrucelli, Leon ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
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Lund University