Toshifumi Yokota

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Toshifumi Yokota
横田俊文
Born
Morioka, Japan
EducationUniversity of Tokyo
Awards
  • The Friends of Garrett Cumming Research & Muscular Dystrophy Canada Endowed Research Chair
  • The Henri M. Toupin Chair in Neurological Science
Scientific career
Institutions

Toshifumi (Toshi) Yokota (Japanese: 横田俊文, romanized: Yokota Toshifumi) is a medical scientist and professor of medical genetics at the University of Alberta, where he also holds the Friends of Garrett Cumming Research & Muscular Dystrophy Canada Endowed Research Chair and the Henri M. Toupin Chair in Neurological Science.[1] He is best known for his studies of antisense oligonucleotide-based therapeutics for muscular dystrophy that led to the development of an FDA-approved drug viltolarsen.[2][1] His research interests include precision medicine for muscular dystrophy and genetic diseases.[3][4] He has co-edited two books both published in the Methods in Molecular Biology series from Humana Press, Springer-Nature,[5][6] and has published more than 100 refereed papers and patents.[7] He is a member of the editorial boards for the International Journal of Molecular Sciences, Genes, Frontiers in Genome Editing, and Nucleic Acid Therapeutics [8][9][10] a member of the Medical and Scientific Advisory Committee of Muscular Dystrophy Canada,[11] and a co-founder of the Canadian Neuromuscular Network (CAN-NMD).[12]

Biography[]

Yokota was born in Morioka, a city in Iwate Prefecture, and raised in multiple cities including Tsu, Mie and Nerima, Tokyo, in Japan.[13][3] He was initially interested in astrophysics; however, his interests changed after taking a genetics class and hearing about gene therapy research for muscular dystrophy at the University of Tokyo.[3] After receiving research training at the University of Tokyo and the , he received his Ph.D. in Biological Science, where he studied the mechanisms underlying skeletal muscle regeneration.[13][3] He completed his post-doctoral training at Imperial College London, Hammersmith Hospital Campus as a Research Fellow of the Japan Society for the Promotion of Science.[14][13] He was a Research Associate at the Children's National Medical Center before joining the University of Alberta.[15] Currently, he is a tenured Professor at the University of Alberta Faculty of Medicine and Dentistry, serving as the Friends of Garrett Cumming Research & Muscular Dystrophy Canada Endowed Research Chair and the Henri M. Toupin Chair in Neurological Science since 2011.[16][1]

Major contributions[]

Yokota's research focuses on precision health and personalized genetic medicine using single strands of artificial DNA/RNA-like molecules called antisense oligonucleotides for neuromuscular diseases.[2] His study demonstrated the therapeutic potential of antisense oligonucleotides for exon skipping, which can be designed to frame-disrupting exons and restore the reading frame and function of a mutated gene by modulating pre-mRNA splicing, leading to the improvement of skeletal muscle function accompanied by dystrophin restoration for the first time in a severe animal model of Duchenne muscular dystrophy (DMD).[17][18][19] Based on his study, viltolarsen, a phosphorodiamidate morpholino oligomer antisense oligonucleotide, was developed for the treatment of DMD in collaboration with a Japanese pharmaceutical company Nippon Shinyaku (also known as NS Pharma).[1][4] Viltolarsen was later approved by the Pharmaceuticals and Medical Devices Agency in Japan and by the FDA in the United States in March and August 2020, respectively, after clinical trials conducted in Japan, Canada, and the United States.[20] His team further developed a potential treatment for nearly half of DMD patients using multiple antisense oligonucleotides, and demonstrated therapeutic effects in a dystrophic mouse model.[21][22] In addition, his team developed a cocktail of peptide-conjugated morpholinos (PPMOs) and restored expression of dystrophin in the myocardium and Purkinje fibers in the heart muscle of a dystrophic animal model.[23] In 2021, his team developed eSkip-Finder, a machine learning-mediated free online application with a database of antisense oligonucleotides to facilitate the design of antisense oligonucleotides that can be used for exon skipping targeted for various genes and exons.[24][25][26]

Supported by the Canadian Institutes of Health Research, his team is also developing antisense oligonucleotide-mediated therapy for facioscapulohumeral muscular dystrophy.[27] In 2020, he identified antisense oligonucleotides called gapmers that knock down the expression of a toxic gene called DUX4 in cell and mouse models for the treatment of facioscapulohumeral muscular dystrophy.[28][29]

Honors[]

  • Research Fellow of the Japan Society for the Promotion of Science (2003-2005)[14]
  • National Institutes of Health Ruth L. Kirschstein National Research Service Award (2010)[30]
  • The Friends of Garrett Cumming Research & Muscular Dystrophy Canada Endowed Research Chair (2011-)[16][1]
  • The Henri M. Toupin Chair in Neurological Science (2011-)[16][1]
  • Canadian Institutes of Health Research China-Canada Joint Health Research Initiative Award (2013)[31]

Selected publications[]

  • Yokota T, Lu QL, Partridge T, Kobayashi M, Nakamura A, Takeda S, Hoffman E. Efficacy of morpholino systemic exon-skipping in Duchenne dystrophy dogs. Ann. Neurol., 2009, 65:667-76.
  • Echigoya Y, Lim K, Trieu N, Bao B, Miskew B, Vila MC, Novak JS, Hara Y, Lee J, Touznik A, Mamchaoui K, Aoki Y, Takeda S, Nagaraju K, Mouly V, Maruyama R, Duddy W, Yokota T. Quantitative antisense screening and optimization for exon 51 skipping in Duchenne muscular dystrophy. Mol Ther. 2017, 25(11): 2561-2572.
  • Echigoya Y, Nakamura A, Aoki Y, Nagata T, Kuraoka M, Urasawa N, Panesar D, Iversen P, Kole R, Maruyama R, Partridge T, Takeda S, Yokota T. Effects of systemic multi-exon skipping with peptide-conjugated morpholinos in the heart of a dog model of Duchenne muscular dystrophy. Proc. Natl. Acad. Sci. U S A., 2017, 114 (16), 4213-4218.
  • Lim K, Echigoya Y, Nagata T, Kuraoka M, Kobayashi M, Aoki Y, Partridge T, Maruyama R, Takeda S, Yokota T. Efficacy of multi-exon skipping treatment in Duchenne muscular dystrophy dog model neonates. Mol. Ther. 2019, 27(1): 76-86.
  • Echigoya Y, Lim K, Melo D, Bao B, Trieu N, Mizobe Y, Maruyama R, Mamchaoui K, Tanihata J, Aoki Y, Takeda S, Mouly V, Duddy W, Yokota T. Exons 45-55 skipping using mutation-tailored cocktails of antisense morpholinos in the DMD gene. Mol. Ther. 2019, 27(11): 2005-17.
  • Lim K, Maruyama R, Echigoya Y, Nguyen Q, Khawaja H, Chandra S, Jones T, Jones P, Chen Y, Yokota T. Inhibition of DUX4 expression with antisense LNA gapmers as a therapy for facioscapulohumeral muscular dystrophy. Proc. Natl. Acad. Sci. U S A. 2020, 117 (28), 16509-16515.
  • Lim K, Bittel A, Maruyama R, Echigoya Y, Nguyen Q, Huang Y, Dzierlega, Zhang A, Chen Y, Yokota T. DUX4 transcript knockdown with antisense 2’-O-methoxyethyl gapmers for the treatment of facioscapulohumeral muscular dystrophy. Mol. Ther. 2021, 29(2): 848-58.
  • Chiba S, Lim K, Sheri N, Anwar S, Erkut E, Shah A, Aslesh T, Woo S, Sheikh O, Maruyama R, Takano H, Kunitake K, Duddy W, Okuno Y, Aoki Y, Yokota T. eSkip-Finder: a machine learning-based web application and database to identify the optimal sequences of antisense oligonucleotides for exon skipping. Nucleic Acids Res. 2021, 49(W1):W193-W198.

References[]

  1. ^ a b c d e f "FDA approves new drug to treat common form of muscular dystrophy based on research from University of Alberta". MirageNews.com. 9 October 2020. Retrieved 20 August 2021.
  2. ^ a b "U of A Researchers Find Possible Relief for Muscular Dystrophy Patients". edmonton.ctvnews.ca. Retrieved 19 August 2021.
  3. ^ a b c d 4581857. "HEROES - Spring 2016". Issuu. Retrieved 17 August 2021.{{cite web}}: CS1 maint: numeric names: authors list (link)
  4. ^ a b "A New Precision-Medicine Therapy for Duchenne Muscular Dystrophy Recently Approved by the FDA, Nearing Approval in Canada". Patient Worthy. 28 October 2020. Retrieved 20 August 2021.
  5. ^ Yokota, Toshifumi; Maruyama, Rika, eds. (2020). Gapmers. Methods in Molecular Biology. Vol. 2176. doi:10.1007/978-1-0716-0771-8. ISBN 978-1-0716-0770-1. ISSN 1064-3745. S2CID 221372639.
  6. ^ Yokota, Toshifumi; Maruyama, Rika, eds. (2018). Exon Skipping and Inclusion Therapies. Methods in Molecular Biology. Vol. 1828. doi:10.1007/978-1-4939-8651-4. ISBN 978-1-4939-8650-7. ISSN 1064-3745. S2CID 52141624.
  7. ^ "Toshifumi Yokota". scholar.google.com. Retrieved 19 August 2021.
  8. ^ "International Journal of Molecular Sciences". www.mdpi.com. Retrieved 18 August 2021.
  9. ^ "Genes". www.mdpi.com. Retrieved 18 August 2021.
  10. ^ "Frontiers in Genome Editing". www.frontiersin.org. Retrieved 18 August 2021.
  11. ^ "Medical and Scientific Advisory Committee". Muscular Dystrophy Canada. 24 July 2019. Retrieved 31 August 2021.
  12. ^ "Neuromuscular disease network to enhance Canadian research and patient care". www.ualberta.ca. Retrieved 8 September 2021.
  13. ^ a b c "Toshifumi Yokota". www.ualberta.ca. Retrieved 17 August 2021.
  14. ^ a b "【研究者データ】横田俊文". 日本の研究.com. Retrieved 19 August 2021.
  15. ^ "Edmonton researchers at the University of Alberta have found a way to regrow a protien [sic] missing in Duchenne muscular dystrophy in mice". edmontonsun. Retrieved 18 August 2021.
  16. ^ a b c "Seeking a cure for muscular dystrophy". WCHRI. 16 May 2020. Retrieved 20 August 2021.
  17. ^ "Researchers Develop DNA "Patch" For Canine Form of Muscular Dystrophy". National Institutes of Health (NIH). 28 August 2015. Retrieved 17 August 2021.
  18. ^ Yokota, Toshifumi; Lu, Qi-Long; Partridge, Terence; Kobayashi, Masanori; Nakamura, Akinori; Takeda, Shińichi; Hoffman, Eric (June 2009). "Efficacy of systemic morpholino exon-skipping in Duchenne dystrophy dogs". Annals of Neurology. 65 (6): 667–676. doi:10.1002/ana.21627. ISSN 1531-8249. PMC 5951302. PMID 19288467.
  19. ^ "First treatment for muscular dystrophy in sight: Scientists successfully harness exon-skipping". medicalxpress.com. Retrieved 20 August 2021.
  20. ^ "VILTEPSO™ (viltolarsen) injection Now Commercially Available in the U.S." Associated Press NEWS. 19 August 2020. Retrieved 22 August 2021.{{cite web}}: CS1 maint: url-status (link)
  21. ^ "A DNA 'Stitch' as a Therapy for Duchenne Muscular Dystrophy". Labroots. Retrieved 25 August 2021.
  22. ^ "Researchers developing new 'DNA stitch' to treat muscular dystrophy: Experimental treatment has potential to help almost half of patients with Duchenne muscular dystrophy". ScienceDaily. Retrieved 19 August 2021.
  23. ^ Echigoya, Yusuke; Nakamura, Akinori; Nagata, Tetsuya; Urasawa, Nobuyuki; Lim, Kenji Rowel Q.; Trieu, Nhu; Panesar, Dharminder; Kuraoka, Mutsuki; Moulton, Hong M.; Saito, Takashi; Aoki, Yoshitsugu (18 April 2017). "Effects of systemic multiexon skipping with peptide-conjugated morpholinos in the heart of a dog model of Duchenne muscular dystrophy". Proceedings of the National Academy of Sciences. 114 (16): 4213–4218. doi:10.1073/pnas.1613203114. ISSN 0027-8424. PMC 5402437. PMID 28373570.
  24. ^ "eSkip-Finder". eskip-finder.org. Retrieved 19 August 2021.
  25. ^ Chiba, Shuntaro; Lim, Kenji Rowel Q.; Sheri, Narin; Anwar, Saeed; Erkut, Esra; Shah, Md Nur Ahad; Aslesh, Tejal; Woo, Stanley; Sheikh, Omar; Maruyama, Rika; Takano, Hiroaki (2 July 2021). "eSkip-Finder: a machine learning-based web application and database to identify the optimal sequences of antisense oligonucleotides for exon skipping". Nucleic Acids Research. 49 (W1): W193–W198. doi:10.1093/nar/gkab442. ISSN 1362-4962. PMC 8265194. PMID 34104972.
  26. ^ "Health Innovation Roundup". Health Cities. Retrieved 19 August 2021.
  27. ^ Government of Canada, Canadian Institutes of Health Research (20 November 2008). "Funding Decisions Database". webapps.cihr-irsc.gc.ca. Retrieved 20 August 2021.
  28. ^ Lim, Kenji Rowel Q.; Maruyama, Rika; Echigoya, Yusuke; Nguyen, Quynh; Zhang, Aiping; Khawaja, Hunain; Sen Chandra, Sreetama; Jones, Takako; Jones, Peter; Chen, Yi-Wen; Yokota, Toshifumi (14 July 2020). "Inhibition of DUX4 expression with antisense LNA gapmers as a therapy for facioscapulohumeral muscular dystrophy". Proceedings of the National Academy of Sciences. 117 (28): 16509–16515. doi:10.1073/pnas.1909649117. PMC 7368245. PMID 32601200.
  29. ^ "Researchers develop potential new therapy for common form of muscular dystrophy". News-Medical.net. 29 June 2020. Retrieved 23 August 2021.
  30. ^ "Federal RePORTER - Project Details". federalreporter.nih.gov. Retrieved 18 August 2021.
  31. ^ Government of Canada, Canadian Institutes of Health Research (20 November 2008). "Funding Decisions Database". webapps.cihr-irsc.gc.ca. Retrieved 20 August 2021.

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