Research Projects :

1. Understanding of pathogenesis of the genetic diseases, particularly lysosomal storage diseases(LSD).
   
2. To establish the novel treatment procedures such as enzyme replacement therapy(ERT), chaperon therapy, New anti-oligonucleotide(AON) therapy (PTC), Cell therapy/Gene Therapy.
   1. Hematopoetic Stem Cell Transplantation
      Hurler, Hunter, Gaucher, Krabbe, MLD etc
   2. Enzyme Replacement Therapy: Now, six lysosomal diseases can be treated:
   3. Small molecules: Substrate Deprivation Therapy & Chaperon therapy, Butylnojirimycin (Migulstat), Genz , Noev
   4. Gene Therapy：Viral Vectors (AAV, Adenovirus, Retrovirus , Lenti virus), Ex Vivo, in Vivo Therapy
   5. Cell Therapy
      • Neural Stem Cell Therapy : Injection via Ventricle/I.V.
      • Mesenchymal Stem Cell Therapy, i.v.
      • Induced Pluripotent stem cells from fibroblasts ( Yamanaka, 2007) (iPS) and ES cells　4) Microglia cell
3. To establish new technology of induced pluripotent stem cells (iPS) from various LSD :Understanding of pathophysiology of LSD and New therapy

   
   We could successfully isolated iPS cells from twitcher, Fabry and Sly mice Skin Fibroblasts- Can Differentiated into Many Cells UsingTail-tip Fibroblasts and Mouse Embryonic Fibroblasts, hKlf4、hSox2、hc-Myc、and hOct , 4 factors were used and also Myc was also deleted to isolate iPS .( Mao, Shen, Ohashi, Eto, 2008)

4. To evaluate the efficacy of ERT; long term efficacy of LSD

   
   Enzyme Uptake mechanism in Gaucher disease through mannose receptor mediated System. High mannose-6-phosphate enriched enzymes are high uptake. Antibody formation will also inhibit the uptake of enzyme by the cells.

5. To develop New treatment for CNS involvement in LSD and other Genetic Diseases Generally, ERT do not have an efficacy to neurological improvement.

   A. Enzyme replacement therpay

   1. High Dose of Enzyme Administration: Type III Gaucher, MPS-I and II ( 100-200 U/kg)
   2. Intrathecal Administration of Enzyme in Gaucher、 MPS I (Hurler etc)
   3. Modification of Enzyme molecules attached some peptides/poly Sialic acid to cross Blood Brain Barrier(BBB)- Under investigation

   B. Gene therapy/Cell Therapy to CNS

   • Gene therapy: AAV, Lenti virus vectors
   • Cell Therapy: Neural stem cells, Mesenchymal stem cells, iPS etc
6. To establish new screening procedures of LSD by dried blood spots and others.

   
   Screening Development of Pompe disease by Dry blood spots(DBS)

7. To understand the current status of LSD patients such as QOL, ADL etc.
8. Others