Study for autophagy in lysosomal diseases and development of drug screening

• Project/Area Number: 25461543
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Osaka University
• Principal Investigator: Sakai Norio 大阪大学, 医学(系)研究科(研究院), 教授 (30314313)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: Krabbe disease / galactosialidosis / Fabry disease / autophagy / chaperone / クラッベ病 / ガラクトシアリドーシス / ファブリー病 / オートファジー / シャペロン / ムコリピドーシス / プロセッシング / ライソゾーム酵素

Outline of Final Research Achievements

Lysosomal diseases are rare and intractable disease and are targets of Japanese health science. However the treatment method are limited such as enzyme replacement therapy and hematopoietic stem cell transplantation which might has severe adverse effect. In this study we performed basic research for Krabbe disease, galactosialidosis and Fabry disease for the screening the low molecule oral drug candidates. With this research we found several cellular pathology for lysosomal diseases and the possibility of chaperone treatment and basic mechanism of it.
With these results it is applied to check the effect of candidate drug in cellular level and the screen the drug for each mutation of the disease.

Research Products

• [Journal Article] Chemical chaperone treatment for galactosialidosis: Effect of NOEV on <beta>-galactosidase activities in fibroblasts (2015)
  • Author(s): Hossain AM
  • Journal Title: Brain Dev Volume: 38 Issue: 2 Pages: 175-180
  • DOI: 10.1016/j.braindev.2015.07.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Chaperone therapy for Krabbe disease: potential for late-onset GALC mutations. (2015)
  • Author(s): Hossain M
  • Journal Title: J Hum Genet Volume: 60 Issue: 9 Pages: 539-540
  • DOI: 10.1038/jhg.2015.61
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Late-onset Krabbe disease is predominant in Japan and its mutant precursor protein undergoes more effective processing than the infantile-onset form. (2014)
  • Author(s): Hossain MA, Otomo T, Saito S, Ohno K, Sakuraba H, Hamada Y, Ozono K, Sakai N
  • Journal Title: Gene Volume: 534 Issue: 2 Pages: 144-54
  • DOI: 10.1016/j.gene.2013.11.003
  • Peer Reviewed
• [Journal Article] Efficacy of deep brain stimulation in an adolescent patient with DYT11 myoclonus-dystonia (2014)
  • Author(s): 2.Kimura Y, Mihara M, Kawarai T, Kishima H, Sakai N, Takahashi M and Mochizuki H
  • Journal Title: Neurology and Clinical Neuroscience Volume: 2 Issue: 2 Pages: 57-59
  • DOI: 10.1111/ncn3.75
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A novel homozygous GALC mutation: Very early onset and rapidly progressive Krabbe disease. (2013)
  • Author(s): Kardas F, Uzak AS, Hossain A, Sakai N, Canpolat M, Yıkılmaz A.
  • Journal Title: Gene Volume: 517 Issue: 1 Pages: 125-7
  • DOI: 10.1016/j.gene.2012.12.040
  • Peer Reviewed
• [Presentation] Krabbe 病患者の病型は 2 つの変異の COS7 細胞での発現実験における galactocerebrosidase 活性の総和と相関する (2015)
  • Author(s): 苛原 香, 大友孝信, 近藤秀仁, 濱田悠介, Hossain Mohammad Arif, 大薗恵一 , 酒井規夫
  • Organizer: 第 57 回日本先天代謝異常学会総会
  • Place of Presentation: 大阪国際会議場、大阪府大阪市
  • Year and Date: 2015-11-12
• [Presentation] クラッベ病に対するケミカルシャペロン (2014)
  • Author(s): 酒井規夫、ホセイン モハマッド・A
  • Organizer: 第５９回日本人類遺伝学会
  • Place of Presentation: 船堀
  • Year and Date: 2014-11-19 – 2014-11-22
• [Presentation] Chemical chaperone treatment for galactosialidosis: chaperone effect of NOEVon β-galactosidase activities in galactosialidosis fibroblasts (2014)
  • Author(s): M A Hossain, K Higaki, M Shinpo, E Nanba, Y Suzuki, M Alfadhel, K Ozono, N Sakai
  • Organizer: SSIEM
  • Place of Presentation: ウイーン、オーストリア
  • Year and Date: 2014-09-02 – 2014-09-05
• [Presentation] Outcomes of hematopoietic stem cell transplantation for three patients with metachromatic leukodystrophy (2013)
  • Author(s): Michiko Shinpo, Sayaka Nakano, Yusuke Hamada, Kouji Tominaga, Shin Nabatame, Takeshi Okinaga, Yoshiko Hashii, Norio Sakai, Keichi Ozono
  • Organizer: ACIMD
  • Place of Presentation: Makuhari
• [Presentation] NOEV treatment option for Japanese Krabbe disease (2013)
  • Author(s): Mohammad Arif Hossain1, Katsumi Higaki2, Eiji Nanba2, Yoshiyuki Suzuki3, Keiichi Ozono1, Norio Sakai1
  • Organizer: ACIMD
  • Place of Presentation: Makuhari
• [Presentation] CHAPERONE THERAPY FOR KRABBE DISEASE; JAPANESE LATE-ONSET MUTATIONS CAN BE TREATED EFFECTIVELY BY NOEV (2013)
  • Author(s): Hossain MA1, Higaki K2, Nanba E2, Suzuki Y3, Ozono K1, Sakai N
  • Organizer: ICIEM2013
  • Place of Presentation: Barcelona, Spain