UCBC survival

[zoki83]

Dr.Young,

In your studies done on animals with UCBC and lithium, how long have the cells shown to survive alone, and how long in combination with lithium? Also a question in regards to the China SCINet phase 3 trial, will a person be excluded from the trial protocol if they are already taking lithium for depression? Thanks for your reply in advance.

[Wise Young]

Dr.Young,

In your studies done on animals with UCBC and lithium, how long have the cells shown to survive alone, and how long in combination with lithium? Also a question in regards to the China SCINet phase 3 trial, will a person be excluded from the trial protocol if they are already taking lithium for depression? Thanks for your reply in advance.

We are actually trying to answer the first question concerning UCBC survival right now. Yes, we have transplanted neonatal rat blood cells and human UCBC into the spinal cord and shown that they survive only if we give cyclosporin or other immunosuppressants. If we don't use immunosuppression, the cells do not survive beyond four weeks. So, we have developed an isogenic strain of rats that express green fluorescent protein, and showed that cells can be transplanted from one rat to another without immunosuppression. We are now looking to see how long such cells survive in rats. Note that in the human studies, we are planning to use HLA-matched cells.

Yes, we will exclude people who are already taking lithium. The reason is that this will prevent us from randomizing the patient to lithium. We are currently excluding patients who are taking lithium from the phase 1 and 2 trial on lithium.

Wise.

[zoki83]

Dr.Young,

In regards to what you have wrote before about combination therapies and there be a source of long term growth factors that make up one part of that combination, I was just wondering is the 6 weeks that you plan to give patients lithium with UCBC long enough to give the axons enough long term growth factors? Will the 6 weeks of taking lithium work to stimulate the axons for only 6 weeks, or shall it continue for a while afterwards?

[Wise Young]

Dr.Young,

In regards to what you have wrote before about combination therapies and there be a source of long term growth factors that make up one part of that combination, I was just wondering is the 6 weeks that you plan to give patients lithium with UCBC long enough to give the axons enough long term growth factors? Will the 6 weeks of taking lithium work to stimulate the axons for only 6 weeks, or shall it continue for a while afterwards?

zok,

I don't know. The clinical trial will tell us whether 6 weeks is enough. We had to choose a time. There are arguments for doing it for 6 weeks or longer.

Wise.

[zoki83]

Dr.Young,

When shall you be publishing your studies that you have done with ucbc and lthium on rats? Also, if you can say, have the results that you have seen been significant enough for you to think that humans might receive signoficant return from this combination? Thanks.

[Wise Young]

Dr.Young,

When shall you be publishing your studies that you have done with ucbc and lthium on rats? Also, if you can say, have the results that you have seen been significant enough for you to think that humans might receive signoficant return from this combination? Thanks.

We are still doing the studies right now. I believe that all three components of the therapy will be necessary for the best recovery: cellular bridge, growth factor stimulation, and axon growth inhibitor blockers.

To date, lithium alone, neonatal rat blood cell alone, and neonatal rat blood cells plus lithium do not seem to improve walking in the rats. However, all these studies used cyclosporin. We recently discovered that cyclosporin antagonizes the effects of lithium. Therefore, we had to develop a source of immune-compatible neonatal blood cells for rats that do not require cyclosporin to survive. These are the studies that are currently underway in the laboratory.

Wise.

[zoki83]

To date, lithium alone, neonatal rat blood cell alone, and neonatal rat blood cells plus lithium do not seem to improve walking in the rats.

If this is the case, how come you didn't choose some other type of cells to use in the China SCINet trials? Isn't it pointless testing something that has not shown improvements in rats, or am I missing something?

[Wise Young]

If this is the case, how come you didn't choose some other type of cells to use in the China SCINet trials? Isn't it pointless testing something that has not shown improvements in rats, or am I missing something?

Because four other laboratories have reported that umbilical cord blood cells are beneficial in spinal cord injury models. The only other potential source of GMP source of cells are bone marrow autografts. We are actively investigating this but it will be much more expensive because it will require a local GMP laboratory at each hospital site, a surgery to remove the cells, and several months to grow and prepare the cells.

As I pointed out, the experiments did not work when we used cyclosporin because it antagonized the lithium. In the human trials, because we will be using HLA matched cells, we will not be using any cyclosporin. We are still doing the rat studies where we are not using cyclosporin.

Wise.

[zoki83]

Because four other laboratories have reported that umbilical cord blood cells are beneficial in spinal cord injury models.

Dr.Young,

Sorry to keep bothering you with these questions, but I'm a little confused at what I'm trying to figure out. Are you saying that four laboratories have reported that umbilical cord blood cells are beneficial in spinal cord injury models but your lab found no improvement at all? Or did yourlab find that they benefit spinal cord injury but don't greatly enhance walking function? Thanks.

[Wise Young]

Dr.Young,

Sorry to keep bothering you with these questions, but I'm a little confused at what I'm trying to figure out. Are you saying that four laboratories have reported that umbilical cord blood cells are beneficial in spinal cord injury models but your lab found no improvement at all? Or did yourlab find that they benefit spinal cord injury but don't greatly enhance walking function? Thanks.

Yes, we were not able to see any beneficial effects of the transplants on walking. The other laboratories used human cells and no cyclosporin. We used rat cells and cyclosporin. We are now comparing rat and human cells, with and without cyclosporin.

Wise.