In 2014, I reported on a groundbreaking, but debated Duke stem cell-based clinical trial being launched for autism.
Where does that trial stand today?
The cord blood trial has continued. It is led by Dr. Joanne Kurtzberg, whom I interviewed about cord blood stem cells back in 2013 (see part 1 and part 2), where she provided some fascinating background. It is also notable that on the stem cell autism trial front, other efforts are underway as well.
This week at the World Stem Cell Summit, Dr. Kurtzberg gave us an update on the cord blood stem cell trial for autism. You can see the trial listing for details here. The Marcus Foundation and PerkinElmer, Inc. are collaborators.
The data presented seem very encouraging. In addition to evidence of efficacy, the cord blood transplants were reported to be safe so that’s encouraging as well.. She reported improvements with cord blood treatment of autistic patients across a number of readout assays (p values in parentheses): decreased sensory sensitivity (0.03), increased social communication (0.007), decreased repetitive behavior (0.01) and a decrease in social withdrawal although not significant (0.09).
These results sound exciting. However, as a biomedical scientist I’m still grappling with how an IV infusion of stem cells could help autism.
What could be the mechanism?
Since we do not know the causes of autism spectrum disorder and there are likely to be numerous causal factors of both genetic and non-genetic natures, it is difficult to define how a systemic cellular treatment could meaningfully benefit autistic children. One notion is that a subset of the cord blood cells cross the blood brain barrier, enter the brain, and somehow do something positive for autism there.
While I’m not clear on what that positive thing might be that is specific to autism, Dr. Kurtzberg showed a FISH staining image where at least some IV administered cord blood cells appeared to have entered the brain. This suggests that the Duke team is thinking at least in part of a direct mechanism.
I believe this particular example was in an allogeneic setting with male cells given to a female patient and the male cells were detected by DNA FISH. There has been much skepticism over the years on whether IV administered stem cells of any kind cross the blood brain barrier (BBB) and how they might do so. In some pathological states it has been shown that the BBB is compromised allowing for stem cells to enter the brain from the vasculature, but I’m not aware of the BBB being compromised in autism. Since there is no apparent inflammation in autism it also remains unlikely that the cord blood stem cells would home in on the brain.
Many open questions remain such as those mentioned above. Also I would like to learn more about the specific numbers of cord blood cells that entered the brain including info such as engraftment rate, timeline, etc. This may have been presented and I just missed it as I was multitasking up a storm at the meeting.
The bottom line for me is that I’m glad to see encouraging results on the autism front, but I still have some skepticism because I do not see a convincing mechanism. Hopefully things will continue on a positive trend and provide more clarity.