Our goal is to develop a cellular strategy for repairing the damage seen in children's myelin disease, Multiple Sclerosis and other neurological diseases.

 
Dear Wayne and Julie,

Margaret and I wish you and your family a happy holiday season.

Following items are intended for the newsletter of the Canadian Myelin Research Initiative:

I trust that the copies of our recent publications I sent you last week are in your hand now.

1.One of the papers on cell/gene therapy in mucopolysaccharidosis VII (Sly disease) mice must be interest to you. This work has been a collaboration between my self and Prof. Eto of Tokyo, Japan (he is an outstanding medical geneticist/ paediatrician specializing lysosomal storage diseases such as Krabbe, Gauchet and ALD) and we wish to continue our collaboration in same lines of work in paediatric storage diseases using human neural stem cells I generated in Vancouver. Next target diseases we are planning are Krabbe and ALD; mouse models of these diseases are available now.

2. As I informed you earlier, we have generated a new human neural stem cell line using a tetracyclin-regulatory gene expression system. This new human cell line multiplies only in the presence of tetracyclin (Tet), and in the absence of Tet most of these cells differentiate into neurons. We could grow them in large numbers in culture in the presence of Tet, modify them to carry a gene of our interest, and then transplant them into the brain of animal models or even in human patients.

We will explore more into the cell/gene therapy using this new human neural stem cell system.

3. Recently we have generated immortalized human mesenchymal stem cell lines (from human foetal bone marrow). These human mesenchymal stem cells become bone cartilage; muscle or neurons depend on their culture environment (a manuscript is in preparation). We will study further their ability to develop into neurons but also into insulin producing beta islet cells, heart muscle cells or liver cells.

4. More recently we have generated oligodendrocytes/oligo progenitors from our human neural stem cells using a master gene called Olig2 transcription factor. Until recently we could not generate oligodendrocytes from our immortalized human neural stem cells probably because of the absence of an oligo-inducing signal in the system/environment. Now we found the signal that tells neural stem cells to become oligodendrocytes. We will pursue this line of work further in New Year by transplanting neural stem cell-derived human oligos in an animal model of MS.

5. We have collaborative works at UBC including transplantation of human neural stem cells carrying brain-derived growth factor gene (these cells produce a large amount of BDNF/neurotrophic factor that keeps host neurons and grafted neurons survive well) into rat model of spinal cord injury (Dr. Wolf Tetzlaff has a spinal cord injury model) and also mouse model of Huntington disease (Dr. Bruce Levitte of UBC has a mutant mouse model of HD).

6. We have a mouse model of ALS in Suwon, Korea and we have transplanted LacZ-labelled human neural stem cells via tail vein and found survival of grafted cells in the neocortex, hippocampus and spinal cord (only small number of cells in spinal cord) and the animal behaviour was visibly improved. We are continuing further experiments in ALS animals by grafting neural stem cells directly into spinal cord.

7. As I sent you copies of two papers earlier in which rat models of stroke were given human neural stem cell transplantation via tail vein injection. LacZ-labelled neural stem cells found their way to the stroke lesions, integrated into the host brain and improved behaviour. Further study is planned to use neural stem cells carrying BDNF gene (see above).

8. In collaboration with Dr. Karen Aboody (formerly of Harvard Neurosurgery and fellow of Evan Snyder, and now at the City of Hope Medical Center near LA), we generated new cell line by modifying our human neural stem cells to carry a suicide gene called cytosine deaminase (F3.CD cell line). Our neural stem cell line was found to track down brain tumour cells selectively and penetrate into the tumour mass. Brain tumour bearing animals are grafted with F3.CD cells, then non-toxic drug fluorocytosine is injected intraperitoneal route, drug reaches to the tumour site and the CD enzyme in F3 cells turn the drug into fluorouracil, a potent anticancer drug. Fluorouracil kills the F3 neural stem cells but the drug diffuses out into wide surrounding area and kills target brain tumour cells via by-stander effect. Earlier studies using mouse neural stem cells showed 90% reduction in tumour size.

I wish to tell you that Margaret and I are most grateful to you for your support, financial as well as moral, during the past several years for our research effort at UBC. If I can be of help in any way to support your good work with Canadian Myelin Research Initiative, I would do my utmost to help you.

With kindest regards, Seung Kim


posted by Canadian Myelin Research Initiative at 3:03 PM