Preclinical study for the therapeutic application of botulinum neurotoxin to intractable brain disorders.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21380188
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied veterinary science
• Research Institution: Osaka Prefecture University
• Principal Investigator: KOZAKI Syunji 大阪府立大学, 生命環境科学研究科, 教授 (10109895)
• Co-Investigator(Kenkyū-buntansha): TAKEUCHI Tadayoshi 大阪府立大学, 生命環境科学研究科・獣医学専攻, 教授 (00171611) ; MIYAKE Masami 大阪府立大学, 生命環境科学研究科・獣医学専攻, 教授 (10251175) ; KATOH Keiko 京都産業大学, 総合生命科学部, 教授 (90252684) ; NAKAJIMA Hidemitsu 大阪府立大学, 生命環境科学研究科・獣医学専攻, 准教授 (30405360)
• Project Period (FY): 2009 – 2011
• Keywords: 疾病予防・制御 / 新規治療薬開発

Research Abstract

To explore the possible clinical applications of botulinum neurotoxin to intractable brain disorders, we investigated whether or not the benefits of A2-botulinum neurotoxin(A2NTX) or cell-permeable C3 enzyme(Tat-C3) are exerted in several intractable brain disorders-model in rodents. Here we show the potent effectiveness of A2NTX against several types of seizer in mice or of 6-OHDA-elicited parkinsonian-like motor dysfunctions in rats. Additionally, preliminary study using brain ischemia indicates the neuroprotective effects in rats treated with Tat-C3.These results suggest that both A2NTX and Tat-C3 may indicate the beneficial possibility of medical treatments with intractable brain disorders such as epilepsy, Parkinson disease, and ischemic stroke.

Research Products

• [Journal Article] A rapid, targeted, neuron-selective, in vivo knockdown following a single intracerebroventricular injection of a novel chemically modified siRNA in the adult rat brain (2012)
  • Author(s): Nakajima, H., Kubo, T., Semi, Y., Itakura, M., Kuwamura, M., Izawa, T., Azuma, YT., Takeuchi, T.
  • Journal Title: J. Biotech Volume: 157 Pages: 326-333
  • Peer Reviewed
• [Journal Article] Charavterization of the monoclonal antib ody response to botulinum neurotoxin ty peA in in complexed and uncomplexed forms (2012)
  • Author(s): Zhao, H., Nakamura, K., Kohda, T., Mukamoto, M., Kozaki, S.
  • Journal Title: Jpn. J. Infect. Dis Volume: 65 Pages: 138-145
  • Peer Reviewed
• [Journal Article] Comparison of effects of botulinum toxin subtype A1 and A2 using twitch tension assay and rat grip strength test (2011)
  • Author(s): Torii Y., Kiyota N., Sugimoto N., Mori Y., Goto Y., Harakawa T., Nakahara Y., Kaji R., Kozaki S., Ginnaga A.
  • Journal Title: Toxicon Volume: 57 Pages: 93-99
  • Peer Reviewed
• [Journal Article] Clostridium perfringens enterotoxin interacts with claudins by electrostatic attraction (2010)
  • Author(s): Kimura J, Abe H, Kamitani S, Toshima H, Fukui A, Miyake M, Kamata Y, Sugita-Konishi Y, Yamamoto S, Horiguchi Y
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 401-408
  • Peer Reviewed
• [Journal Article] Characterization of the membrane-targeting domain in Pasteurella multocida toxin (2010)
  • Author(s): Kamitani S, Kitadokoro K, Miyazawa M, Toshima H, Fukui A, Abe H, Miyake M., Horiguchi Y
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 25467-75
  • Peer Reviewed
• [Journal Article] Association of Bordetella dermonecrotic toxin with the extracellular matrix (2010)
  • Author(s): Fukui-Miyazaki A, Kamitani S, Miyake M, Horiguchi Y
  • Journal Title: BMC Microbiol Volume: 10 Pages: 247
  • Peer Reviewed
• [Journal Article] Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines (2010)
  • Author(s): Nochi T., Yuki Y., Takahashi H., Sawada S., Mejima., Kohda T., Harada N, Kong IG., Sato A., Kataoka N., Tokuhara D., Kurokawa S., Tsukada H., Kozaki S., Akiyoshi K., Kiyono H.
  • Journal Title: Nature Mater Volume: 9 Pages: 572-578
  • Peer Reviewed
• [Journal Article] A novel multiplex PCRmethod for Clostridium botulinum neurotoxi type A gene cluster typing (2010)
  • Author(s): Umeda K., Seto Y., Kohda T., Mukamoto M., Kozaki S.
  • Journal Title: Microbiol Immunol Volume: 54 Pages: 308-312
  • Peer Reviewed
• [Journal Article] Characterization of the D/C mozaic neurotoxin produced by Clostridium botulinum associated with bovine botulism in Japan (2010)
  • Author(s): Nakamura, K., Kohda, T., Umeda, K., Tamamoto, H., Mukamoto, M., Kozaki, S.
  • Journal Title: Vet Microbiol Volume: 140 Pages: 147-154
  • Peer Reviewed
• [Journal Article] Genetic characterization of Clostridium botulinum associated with type B infant botulism in Japan (2009)
  • Author(s): Umeda, K., Seto, Y., Kohda, T., Muk amoto, M., Kozaki, S.
  • Journal Title: J. Clin. Microbiol Volume: 47 Pages: 2720-2728
  • Peer Reviewed
• [Journal Article] Quantification of potency of neutralizing antibodies to botulinum toxin using compound muscle action potential(CMAP) (2009)
  • Author(s): Torii, Y., Takahashi, M., Ishida, S., Goto, Y., Nakahira, S., Harakawa, T., Kaji, R., Kozaki, S., Ginnaga, A.
  • Journal Title: Toxicon Volume: 55 Pages: 662-665
  • Peer Reviewed
• [Journal Article] Distinct Role of Growth Hormone on Epilepsy Progression in a Model of Temporal Lobe Epilepsy (2009)
  • Author(s): Kato K., Suzuki M, Hiroki Kanno H, Sekino S, Kusakabe K, Okada T, Mori T, Yoshida K, and Hirabayashi Y.
  • Journal Title: J. Neurochem Volume: 110 Pages: 509-519
  • Peer Reviewed
• [Presentation] Accell siRNAの単回脳室内投与による脳内の遺伝子サイレンシング効果 (2011)
  • Author(s): 久保岳也、中嶋秀満、瀬見優子、桑村充、井澤武史、東泰孝、竹内正吉
  • Organizer: 第54回日本神経化学会大会
  • Place of Presentation: 加賀
  • Year and Date: 20110900
• [Presentation] An in vitro model system for studying Clostridium perfringens type A infection (2011)
  • Author(s): Hoshi, H., Kondo, K., Oda, M., Nagahama, M., Yamamoto, S., Kamata, Y., Miyake, M.
  • Organizer: International Union Microbiologi cal Sciences 2011 Congress
  • Place of Presentation: 札幌
  • Year and Date: 20110900
• [Presentation] Further characterization of Clostridium botulinum type D/C mos aic neurotoxin (2011)
  • Author(s): Nakamura K., Kohda, T., Mukamoto, M., Kozaki, S.
  • Organizer: International Unio n Microbiological Sciences 2011 Congress
  • Place of Presentation: 札幌
  • Year and Date: 20110900
• [Presentation] Translocation of light chain of Clostridiu m botulinum type B neurotoxin into PC 12 cells (2011)
  • Author(s): Kohda, T., Ihara, H., Mukamoto, M., Kozaki, S.
  • Organizer: International Union Mic robiological Sciences 2011 Congress
  • Place of Presentation: 札幌
  • Year and Date: 20110900
• [Presentation] An in vitro model system for studying Clostridium perfringens type A infection (2011)
  • Author(s): Hoshi, H., and Miyake, M.
  • Organizer: International Conference on Global Issues Influencing Human and Animal Health for ASEAN
  • Place of Presentation: タイ
  • Year and Date: 20110700
• [Presentation] Functional analysis of synaptotagmin II as a receptor for Clostridium botulinum type B neurotoxin (2010)
  • Author(s): Kohda, T., Ihara, H., Mukamoto, M., Kozaki, S.
  • Organizer: The 47^<th> IBR CC meeting
  • Place of Presentation: 米国
  • Year and Date: 20101100
• [Presentation] Applica tion of A2NTX in the treatment of refra ctory epilepsy(抗難治性てんかん剤としてのA2NTXの開発) (2010)
  • Author(s): Kato K., Koda T, Kozaki, S.
  • Organizer: 87^<th> Annual Me eting of the Physiological Society of Japan
  • Place of Presentation: 岩手
  • Year and Date: 20100500
• [Presentation] Characterization of Clostridium botulinu m associated with human and animal b otulinum in Japan (2009)
  • Author(s): Kozaki, S
  • Organizer: 韓国微生物学会
  • Place of Presentation: 韓国
  • Year and Date: 20091000
• [Book] わが国で発生している牛ボツリヌス症由来菌の特徴 (2012)
  • Author(s): 小崎俊司, 幸田知子、中村佳司
  • Publisher: 全国農業共済協会版
• [Book] Introduction of a novel molecular mechanism on epilepsy progression : roles of growth hormone signaling in a mouse model of temporal lobe epilepsy. Underlying mechanisms of epilepsy (2011)
  • Author(s): Kato K
  • Total Pages: 63-76
  • Publisher: Intech-Epilepsy
• [Book] ボツリヌス毒素によるてんかんの治療Application of botulinum neurotoxin in the treatment of epilepsy-BRAIN and NERVE-神経研究の進歩- (2009)
  • Author(s): 加藤啓子, 幸田知子, 小崎俊司
  • Total Pages: 939-948
  • Publisher: 医学書院
• [Book] クロストリジウム神経毒素の受容体認識 (2009)
  • Author(s): 小崎俊司、居原秀
  • Total Pages: 8
  • Publisher: 実験医学羊土社
• [Remarks] ホームページ(小崎俊司)
  • URL: http://www.vet.osakafu-u.ac.jp/epid/epid.html
• [Remarks] ホームページ(三宅眞美)
  • URL: http://www.vet.osakafu-u.ac.jp/pub/pub.html
• [Remarks] ホームページ(加藤啓子)
  • URL: http://www.cc.kyoto-su.ac.jp/～kato/Home_J.html/Welcome.html
• [Remarks] ホームページ(竹内正吉、中嶋秀満)
  • URL: http://www.vet.osakafu-u.ac.jp/pham/pham.html