Last week the FDA approved a trial testing the efficacy of autologous stem cells in ameliorating language deficits and improving behavior in autistic children 2-7 years old.
The good: This will be a randomized, blinded, placebo-controlled, crossover study. This is the way clinical trials should be done. The investigators, subjects and parents do not know whether the subject received their own cord blood cells or saline. Crossover means that all 30 kids in the study will receive stem cells, either that the beginning or at the half way point of the protocol. Behavior will be tested at the outset, at the half way point, and at the end of the trial. Another good point is that several serum cytokines will be assayed at these same time points, so we will know (1) if any subjects had abnormal immune status, at least by the measure of cytokines, and (2) whether the treatment was able to alter this status. Is there any scientific justification for this treatment? In my opinion, the two most relevant animal experiments are those involving injection of bone marrow stem cell in two very different mouse models: one a genetic model of Rett Syndrome and the other a model of an environmental risk factor, maternal infection. I posted comments on these successful experiments here on July 17, 2012. Of course, mice are not humans, but most clinical trials are necessarily based on results from animal studies.
The bad: While it is likely that this treatment will be safe, we can’t be sure since it has not been used in kids with autism before, at least not in a controlled clinical trial. Regardless of outcome, this small trial will provide useful information concerning the safety of this procedure in young children – which will be important in considering this and related treatments for other diseases of young children. Thus, the safety issue could belong in both the good and the bad categories of my analysis. To my mind, a drawback of this trial is that the subjects are to be randomly chosen; I would have preferred to have the autism subjects be chosen for the presence of immune abnormalities, which is what this procedure may be testing. I do not believe that this procedure will result in correcting the wiring of the brain by addition of new cells that migrate into the brain from the blood.
The ugly: Aside from the safety issue, my biggest worry is that if no efficacy is found, stem cell therapy for disorders in young children in general will receive a major setback. That is, the FDA may be reluctant to approve new protocols for other, more promising indications in the case of failure here. Moreover, those that oppose the use of stem cells in general, and those that oppose the use of tax payer dollars to support this type of research in California (by the California Institute of Regenerative Medicine, CIRM) will shout at big, “Told you so!” and increase political pressure to end stem cell research.
CIRM commented on this autism trial, which by the way is not sponsored by CIRM, in a blog titled: “Stem cell trial for autism: hope vs. caution”. Here are some quotes from their blog: “A trial is just that – a trial. More early stage clinical trials fail than succeed. That’s how science moves forward…Science writer Emily Willingham has written about her concerns regarding the science behind this trial. She characterizes the excitement as “stem cells are hot and autism is hot so let’s throw some stem cells at autism”….This is a point we often struggle with at CIRM. That is, when is the right time to take risks…The lead investigator of this trial Michael Chez gives his own reason for why it’s important to be testing blood cells for autism even if the science behind the trail isn’t strong. “…many people are going to foreign countries and spending a lot of money on therapy that may not be valid”. He’s right. CIRM is one of many organizations and individuals who are worried about the rise of stem cell tourism….On our own governing board this tension between funding the very best science and taking risks to push the science forward for life threatening disease comes up routinely. Our patient advocate board members, who make up 10 of the 29 members, sometimes push for funding for science that didn’t get the highest scores from out scientific reviewers. Their point: maybe it’s not a sure thing, but it might help us learn something important.”