Knoepfler Lab Stem Cell Blog, by Paul Knoepfler ~ December 16, 2013
Dr. Charles Cox at the University of Texas (UT) Health Science Center at Houston is starting a new stem cell-based clinical trial for the treatment of young children with cerebral palsy (CP). There is an urgent need for the development of new treatments for CP.
You can learn more about the details of this specific trial here on clinicaltrials.gov.
The purpose of this specific study is to compare the effectiveness and safety of banked cord blood to bone marrow stem cells.
Dr. Cox, who is The Children’s Fund Distinguished Professor and Director, Children’s Program in Regenerative Medicine at UT was kind enough to do an interview with me on the trial.
How did you get interested in the possibility of using stem cells to treat CP?
Pediatric neurologic injury is a terrible, unsolved problem. We started with preclinical work on investigating using stem cells to treat various injuries of this kind in 2002. This work has included traumatic brain injury in children and adults and now we are starting this trial for CP.
Can you please tell us a bit about the design of the trial?
This is a Phase IIa trial in which we will compare two therapies (cord blood and bone marrow) to a placebo control. It is a double blinded study. Neither we nor the parents will know who gets what, but later in the study there is an opportunity for parents to have their kids crossover from placebo. We will give a single dose of 2-10 million cells/kg. That dose was chosen based on a variety of pre-clinical data. Then we will follow the kids for a period of years. Others may take the approach of “we’ll give you a shot for CP and see you later”, but that’s not what we are doing.
How concerned are you about those for-profit clinics that take that “here’s your shot, see you later” approach?
I am concerned. It undermines us and what we are trying to do. We do it by the book, which is very expensive, but it is the best approach. I worry about the degree of oversight at those clinics and about patient assumptions that there may be more oversight than there really is. I also am concerned that if something goes wrong at a clinic like that it may in effect “poison the well” for those of us trying to develop therapies in a rigorous manner following the rules.
What is the rationale for this trial and what mechanisms do you hypothesize could be at work?
This is not a tissue replacement or engraftment or transdifferentiation kind of effect we are looking for. Rather, we think these cousin cell types have the potential to modulate the innate immune response to injury in ways that could be helpful. With injuries such as in CP there can be an out of control immune response that causes further injury. We don’t need all the needles, if you will, in the body turned to the right on immune response. It’s not helpful and is in fact harmful in many cases. There is preclinical data indicating that the ongoing neuroinflammatory response is a driver of further injury in CP so the hope is to reduce this neuroinflammation.
Are there particular challenges for this kind of study?
We aim to enroll 30 patients. There might be 200 families who wish to enroll, but we can’t accommodate that in this study. It’s challenging on one level because these kinds of studies are so expensive. Measuring the outcomes is a very expensive part of the trial.
Another challenge is expectations. Some people might say unless you hit a grand slam homerun, a trial has failed. In fact, even a transient response—which is quite possible—could prove very useful and informative.
An additional challenge is the heterogeneity of CP as there are quite a few different causes, which could affect the response to treatment. Further, we will strive to avoid enrolling kids who have been misdiagnosed with CP, but who really have other conditions that may present in similar ways such as mitochondrial disorders.
How will you follow the kids after treatment?
Our primary readout will be white matter volumetrics in specific regions of the brain. We will assess this by specific advanced form of MRI called 3T DT-MRI. Our secondary readout will be measurements of functional outcomes in the kids.
Do you have specific expectations for the outcomes of the trial?
Our goal is to break the cycle of inflammation and injury. Even a hint of an effect may serve as a foundation for a next step, another trial. There’s this concept of “the adjacent possible”. What this means is that a caveman can’t go straight to the moon, but a NASA team can. Our study may lay the foundation for important future trials as well. In fact, whether our study says the cells are helpful or not, the information will be useful. We need to know what to focus on in the future.