There is a huge interest to cell therapy of cerebral palsy (CP), because these children have no treatment options. The interest is also fueled by the hype around “famous Duke trial” – autologous cord blood transplant for CP. Mass media is filled by case reports of kids from “Duke study”. Cord blood banks are watching it very closely. Will cord blood become the next “big thing” in regenerative medicine? This is a “million dollar question”!
There were no major updates from Duke trial this year. The trial is ongoing and seems enrollment is not progressing well. In a meantime, the results of another trial, conducted in S. Korea, were just reported. I think, the Korean study is a very important milestone in cell therapy of cerebral palsy.
The results of Phase 2 trial, assessing allogeneic cord blood (UCB) transplantation with erythropoetin (EPO) for children with CP, have been published yesterday in Stem Cells. This study was randomized, double-blinded and placebo-controlled. The authors were able to enroll 105 children during 6 months(!) after trial launch. Patients received matched allogeneic cord blood cells + EPO (UCB group, n=31), EPO only + autologous blood as control for UCB infusion (EPO group, n=33) and rehabilitation only (control group, n=32).
The frequency of adverse events didn’t differ between the groups. One case of death was reported in UCB group, but was not “cells-related”. The authors wrote about risks and adverse events:
Considering the overall frequency and severity of the adverse effects in the present study, the risks did not appear to be prohibitive in considering this new approach for CP.
UCB group outperformed both EPO and control groups in multiple functional outcome measures! Younger children showed greater improvements in UCB abd EPO groups. Better HLA-matching, total nucleated cell number and CD34+ cell number directly correlated with better outcome in UCB group.
In conclusion, a single allogeneic cord blood infusion potentiated by EPO, is effective therapeutic modality in children with cerebral palsy, since it results in significant motor and cognitive improvement.
The significance of this study is tremendous! First of all, this is the first published controlled trial, assessing cord blood efficacy in cerebral palsy (One may wonder why NEJM and Lancet didn’t published it). Second, it works! Third, it could be the next “big thing” in use of cord blood in regenerative medicine. Fourth, the correlation between UCB match and efficacy indicates to possible better outcome from autologous transplants. Finally, the release of this study is a big blow for famous “Duke trial”:
The use of cord blood to treat cerebral palsy was pioneered by Dr. Joanne Kurtzberg’s group at Duke Medical Center in the United States. According to a survey by Verter (in preparation for ISCT 2013), since 2005 more children have received cord blood therapy at Duke for acquired neurological disorders than at all other reporting hospitals combined. Yet, nothing has ever been published by the Duke group about the efficacy of cord blood for cerebral palsy. Now, Dr. MinYoung Kim’s group in South Korea is the first to publish controlled data on the efficacy of cord blood for cerebral palsy. Quite frankly, this paper is a scientific coup and a stark demonstration of the global nature of research today.
The biggest disadvantage of the trial is the absence of “UCB only” group. So, we still don’t know whether UCB alone can be as effective as a combination with EPO. Because side effects of EPO treatments (high hemoglobin) were noticed by the authors, one may consider to extend the trial to UCB only group. The authors acknowledge it in discussion. Yet another downside is allogenicity and use of immunosuppression. First, cyclosporin can cause some adverse events (the authors attribute some adverse event in UCB group to immunosuppression) and, second, it can influence the functional outcome (see discussion).
Finally, i’d like to point out that this is the only one of the recent cell therapy trials, which has results published in database (!).
Other trials results, released in 2012
(1) The results of uncontrolled study from India, assessing autologous bone marrow mononuclear cells, was published. 20 children with CP were evaluated and the authors concluded:
Eighty-five percent of cases of cerebral palsy cases showed improvements, out of which 75% reported improvement in muscle tone and 50% in speech among other symptoms.
(2) Placebo-controlled randomized study from China, evaluated 45 patients with CP after intra-cerebral transplantation of allogeneic fetal neural cells. The authors conclude:
Motor development was significantly accelerated within the first month after cell transplantation, but the rate of improvement gradually slowed to preoperative levels. However, after 1 year, the developmental level in each functional sphere (gross motor, fine motor, and cognition) of the treatment group was significantly higher compared to the control group.
Basically, the study demonstrated only moderate effect of cells at some time points in the group with severe CP. If you look at through tables, you can see how children can improve by rehabilitation alone.
The publications of all 3 trials mentioned above, available in open access.
I retrieved some interesting data from clinical trials registries. I’m going to show only 2011-2012 data.
There were 9 trials, assessing cell therapy in cerebral palsy, registered in databases since 2011. The location of trials:
Cell types, used in the trials:
Allogeneic versus autologous donors:
As you can see, in the last 2 years all 9 trials were registered/ launched in Asia. None in America or Europe. The most interesting thing is that all allogeneic trials use cord blood and all of them located in S. Korea!