Cerebral Palsy and Cord blood

[Mrs770]

Dr. Young,

There are currently 5 or 6 clinical trials world wide that are transplanting UBMC into cerebral palsy patients. One is Duke University. I have read anecdotal (sp) reports that there have been exciting results. What is your opinion on these trials.

Secondly, if CP is brain damage at or near birth, what impact could these trials have on TBI?


Thanks!

[rjg]

I'll take a shot at answering these for Wise. As for the trials, he does not know a lot about them(he's too busy defending himself from paolo's slander, curing sci, and fielding jawaid's broken record questions about his limp weenie to concern himself too heavily with cp), but he is familiar with the work of one of the researchers involved and he respects that work tremendously. He is very excited to see what comes out of it all.

As for your second question, it could have an impact. A positive impact.

[rjg]

Also - you're welcome.

[Lyerly]

Originally Posted by rjg

I'll take a shot at answering these for Wise. As for the trials, he does not know a lot about them(he's too busy defending himself from paolo's slander, curing sci, and fielding jawaid's broken record questions about his limp weenie to concern himself too heavily with cp), but he is familiar with the work of one of the researchers involved and he respects that work tremendously. He is very excited to see what comes out of it all.

As for your second question, it could have an impact. A positive impact.

Haha wel played

[Wise Young]

Originally Posted by Mrs770

Dr. Young,

There are currently 5 or 6 clinical trials world wide that are transplanting UBMC into cerebral palsy patients. One is Duke University. I have read anecdotal (sp) reports that there have been exciting results. What is your opinion on these trials.

Secondly, if CP is brain damage at or near birth, what impact could these trials have on TBI?


Thanks!

Mrs770,

Yes, several groups are transfusing cord blood into patients with cerebral palsy. Most of these trials should have results by 2013. I am looking forward to the results, particularly those of the trial by Joanne Kurtzberg at Duke.

If these trials show positive results, this would change thinking about cord blood and what it is doing to the brain. It is hard to imagine how infusing 100 ml of autologous umbilical cord blood into the patient could fix brain damage.

It would have implications for brain injury in general.

Wise.

[LaMemChose]

Originally Posted by Wise Young

Mrs770,

Yes, several groups are transfusing cord blood into patients with cerebral palsy. Most of these trials should have results by 2013. I am looking forward to the results, particularly those of the trial by Joanne Kurtzberg at Duke.

If these trials show positive results, this would change thinking about cord blood and what it is doing to the brain. It is hard to imagine how infusing 100 ml of autologous umbilical cord blood into the patient could fix brain damage.

It would have implications for brain injury in general.

Wise.

With umbilical cord blood, is it necessary for it to be autologous or could UBC come from an immediate relative like a sibling, child, niece/nephew?

[rjg]

I'll be glad to fill in for you here when you're busy curing sci, Dr. Young. I was pretty spot on with this one and I can tell Jawaid the same thing over and over with the best of 'em. Just say the word, pal.

[rjg]

Umbilical cord blood can come from anyone who matches you closely, regardless of whether they are related. There's a test. There are six points possible. Dr. Young and I shoot for a match of at least 4.

[Wise Young]

Originally Posted by LaMemChose

With umbilical cord blood, is it necessary for it to be autologous or could UBC come from an immediate relative like a sibling, child, niece/nephew?

Autologous is the best, of course, because it is the recipient's own blood. Sibling provides the next closest match. In non-identical siblings, the chances of a perfect HLA-match is about 1:4. All people share at least half of their HLA with their parents or children; this is called haploidentical. More than half of the HLA may match if the parents share some HLA. There are some studies suggesting that haploidentical blood/bone marrow match better than 3:6 HLA unrelated blood. The better the match and the closer the relation between the donor and recipient, the greater likelihood of engraftment. There is no guarantee of engraftment, however, even with sibling cord blood or bone marrow.

Cord blood banks can provide HLA-matched unrelated allogeneic cord blood. Most unrelated allogeneic cord blood transplants are done in a setting of bone marrow ablation (myeloablation) and immunosuppression. In such a setting, cord blood that has only 4:6 HLA match with the recipient will engraft 80% of the time. However, myeloablation (chemotherapy) and immunosuppression (cyclosporin) are both quite bad, causing 10-20% mortality rates and infertility of the recipient as well, and may cause a high incidence of graft-versus-host-disease where the transplanted cells attack the host and cause a form of "immune disease". So, most of the treatments of cerebral palsy or brain injuries have been done with autologous cord blood.

In the case of our clinical trials, we are using HLA-matched cord blood that is at least 4:6 match. Some subjects in our study have 5:6 or 6:6 match. We want to correlate the results with the match. From animal studies, we know that human umbilical cord blood cells survive 3-4 weeks when transplanted into the spinal cord of rats without immunosuppression. The cells are usually rejected by 4 weeks. When high-dose cyclosporin is used (i.e. 10 mg/kg/day) is given, the cells usually survive for long periods, indicating that the cells are immune-rejected. Note that these are xenograts (i.e. from one species to another), suggesting that human umbilical cord blood cells are temporarily tolerated by the immune system of rats when transplanted into the spinal cord but they are eventually eliminated.

By the way, neonatal rat blood (the equivalent to human umbilical cord blood) is very fragile compared to human cord blood. They generally do not survive as long when transplanted into the spinal cord than human umbilical cord blood. That is one of the reasons why we have had such a difficult testing the use of human umbilical cord blood mononuclear cells and lithium treatment of rat spinal cord injury. When we used cyclosporin to prevent rejection of the cells, we found that cyclosporin blocked the effects of lithium on the human umbilical cord blood cells. On the other hand, many researchers have reported beneficial effects of human umbilical cord blood cells transplanted into the spinal cord of rats without cyclosporin or other immunosuppressants.

The mechanism by which umbilical cord blood cells may be beneficial for cerebral palsy are unknown. Some investigators (such as Joanne Kurtzberg) has suggested that umbilical cord blood cells will penetrate the blood-brain-barrier and produce new neurons in the brain. Dr. Kurtzberg in fact shows a very interesting picture from one of her patients who died. She showed that there were new neurons in the brain that came from the transplanted umbilical cord blood cells that had been infused. This finding needs to be confirmed in further studies. Unfortunately, as I have pointed out above, this is very difficult to show in animals treated with human umbilical cord blood cells because the cells will be rejected.

Other investigators believe that umbilical cord blood cells produce neurotrophins and other growth factors that may be beneficial for the brain and spinal cord. This is a more likely and reasonable explanation, in my opinion, and the hypothesis that we are posing in our trials of cord blood and lithium treatment of chronic spinal cord injury.

Wise.

[LaMemChose]

Thank you, Wise.