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

 
From Suffolk Life, Wednesday July 2nd, 2003 (via Professor Hersh Chadha)

A study of a new drug called Campath, at Stoney Brook University, in Suffolk England, is accepting participants from the region.

"To date, every patient has shown a predictable response to Campath through suppressed disease activity" said Professor Alistair Compton.

It is hoped the drug will slow or stop the progression of MS.
posted by Canadian Myelin Research Initiative at 11:36 AM

 
Professor Seung U. Kim from the University of British Columbia writes-

Dear Wayne,


I trust that this letter finds you and your family well. It was a long time since I wrote to you and Julie. It is about time the package containing a letter and copies of manuscripts is in your hand. There are several items I would like to inform you of our recent research projects.

Following are the description of projects currently undertaken in the UBC and Ajou University laboratories:

1. Generation and characterization of HB1.F3 immortalized human neural stem cell (NSC) line (Cho et al., Neuroreport 13, 1447-1452, 2002; Ryu et al., J Neurosci Res 72, 352-362, 2003)-support by the Canadian Myelin Research Initiative acknowledged.

2. Generation of F3 human NSC line carrying TH gene and GTP cyclohydrolase I gene. This cell line is found to produce L-DOPA at the level of 400 ng/one million cells/day and to restore functional deficits in rat model of Parkinson disease (a manuscript in preparat5ion).

3. Generation of F3 human NSC line carrying brain-derived neurotrophic factor (BDNF) gene. This cell line was transplanted into the rat brain of Huntington disease model and restored functional deficits (a manuscript submitted, Ryu et al.)- Canadian Myelin Research Initiative acknowledged.

4. F3 huamn NSCs were introduced intravenously via tail vein of rats with experimental stroke model. F3 human NSCs survived in rat brain well and partially restored functional deficits of the animals (a copy of the galley proof is enclosed; Jeong et al., Stroke, in press).

5. F3 human NSC cell line was transduced to carry beta-glucuronidase gene and transplanted into the brain of mucopolysaccharoidosis VII (Sly disease model) mouse and corrected brain pathology (a copy of the paper enclosed, J Neurosci Res � accepted for publication) � support by the Canadian Myelin Research Initiative acknowledged. This is a collabarative study with Prof. Eto of Tokyo.

6. F3 human NSCs were introduced via tail vein of ALS model mice (SOD over-expressing transgenic mice) and found to migrate and integrate into pyramidal cell neuron layer of the CA3 region of hippocampus (F3 human NSCs were not found in spinal cord region since SOD/ALS mice used for the study were too young to demonstrate ALS pathology. In older animals, i.e. 10 weeks old and beyond, we expect that the F3 cells migrate to spinal cord anterior horn region and support survival of host motoneurons). We will do more work in this area, since F3 cells could be a excellent candidate for the cell replacement therapy in human ALS patients.

7. Permanent cell line of human microglia, HMO6 cell line- (Nagai et al., Neurobiol Disease 8, 1057-1068, 2001; a copy enclosed)- Astra-Zeneca Pharmaceutical Company has taken a license of the cell line. Amgen (ompany with 1 billion dollar sale last year) is about to take license of this cell line for discovery of new drugs.

8. Production human CNS neuron-neuroblastoma hybrid neuronal cell line A1 (Nagai et al., Neurobiol Disease 11, 184-198, 2002; a copy enclosed) � both papers acknowledged support of the Canadian Myelin Research Initiative. It is extremely difficult to obtain human neuron population for experimental studies, this cell line is the closest to normal human neurons.

9. Stable immortalized cell lines of human bone marrow stem cells using retroviral vectors carrying v-myc or teromerase catalytic unit (a permanent cell line immortalized by teromerase is close to normal cells as compared to the cell lines carrying v-myc oncogene) were produced and characterized. We were successful in inducing bone, cartilage, adipose tissue and neurons from these human bone marrow stem cell lines (a manuscript in preparation). These cell lines are pluripotent and should have a great potential in generating variety of human tissues/organs for future regenerative medicine.

10. Generation and characterization of human neural crest stem cell line HNC10.K10 cell line (chapters in monographs published in 2002; Nakagawa et al., in: Neural Stem Cells for Brain and Spinal Cord Repair, Humana Press, 2003; Kim et al., in: Neural Stem Cells: Methods and Protocols, Humana Press, 2002)-Both acknowledged support of Canadian Myelin Research Initiative.

11. We are currently investigating a research project ?�Induction of oligodendrocytes from human neural stem cells using Olig2, a cell fate determination gene for oligodendrocytes?�. By introducing plasmids containing Olig2 DNA (gene) into the F3 human neural stem cells, F3 cells became oligodendrocytes. Now it is feasible to generate a large number of human oligodendrocytes from immortalized human neural stem cells and transplant into brain of patients suffering from multiple sclerosis.


Following are items I did not specify in the letter sent you ealier:

12. With the collaboration with Rona Carroll (Brain tumor Research lab, BWH/Harvard), Peter Black (BWH) and Karen Aboody (City of Hope Med. Center), F3 cells were used to track down glioma cells and kill the tumor cells.

Harvard group transduced F3 cells with cytosine deaminase gene, implanted into the rat brain with glioma, then inject fluorocytosine (FC) ip. F3 cells carrying CD convert FC into fluorouracil (FU), FU kills F3 cells and kill tumor cells in vicinity (by-stander effect).

13. We have recently generated human neural stem cell line F3.EGFP. We are currently working to transduce human neural stem cells and human bone marrow stem cells with EGFP-luciferase fusion gene so that in vivo migration and whereabout of implnted cells could easily be visualized by in vivo bioluminescence immaging.

14. Since v-myc transduced human NSC cell line might not be suitable for brain transplantation in human patients (because of v-myc), we recently generatd a line of immortalized human neural stem cells using a tetracyclin-regulated expression of v-myc (tet-on) system. In the presence of doxicyclin stem cells proliferate while in the absence of antibody they differentiate into neurons. This cell line could be used for transplantation in human patients.

I trust that the items I described above could be used for the Newsletter of the Canadian Myelin Research Initiative you are currently editing.



With best regards, Seung Kim

posted by Canadian Myelin Research Initiative at 11:40 PM