Zhao's Stem Cell Educator phase-I trial, which I blogged about here:
has generated a lot of interest, so I've done some extra research on it, and this blog contains what I've learned.
Good News First
The best news that I gathered about this work, is that the published paper is not the final report on a 15 person clinical trial. Is is the initial report on the first 15 people treated in a clinical trial which is on-going and continuing to enroll more people. This is great news, for two reasons. First, because it means that they are continuing to follow those 15 people. With a little luck we can look forward to follow up reports describing what happens to these people in another year, two more years, and so on. Also (again, with some luck) we can expect reports on 50 people, 80 people, maybe even more people. All this data is already being gathered as part of the current clinical trial.
The next good news is that the researchers very much want to start a clinical trial in the US. That will take some time, due to regulatory approvals. If they do start a trial in the US, it is likely to be similar to the one in China [d1].
Several people have asked me how this treatment works, and this is how it was explained to me:
First, there are proteins which train the body's immune system not to attack itself [d2]. These proteins are found on stem cells, so exposing immune system cells to the stem cells has the effect of training the immune cells not to self attack. Second, these researchers believe that there are cells in the pancreas which are ready to become beta cells[d3], and also that there are stem cells circulating in the blood stream [d4] which can turn into beta cells. They don't know which of these two routes are creating the new beta cells, but they believe some combination of them is creating enough beta cells to cause the large decrease in injected insulin and increase in C-peptide.
One question that I had was basically this: "Do you really think that the body can regrow so many beta cells that it can generate 25 to 38% of it's own insulin in just a few weeks? No one else has seen anything like that when using other techniques to stop the autoimmune attack." The answer was that was exactly what they thought was happening. First, it was the theory that explained the results the best, and second, it was what they saw in their animal studies, so they were not surprised to see it in people. We can only hope this is correct. Future trials will tell.
I did ask if there was anything special about stem cells from the umbilical cord, which made that particular type of stem cell important to the research. The response was no. They expected that many types of stem cells would work, but they choose to use umbilical cord cells because they were convenient to use and easy to get, as compared to other types of stem cells.
The researchers have professional connections to researchers in Amman, Jordan and Hue, Viet Nam, and that is why they might start clinical trials in those places. Because there will be fewer regulatory hurdles, those studies could start more quickly than the one in the USA. My feeling was that if they did studies in those place, the studies would be similar to the Chinese one, but they would try to improve ("optimize") the procedure.
Finally, I want to say that I have heard from several different sources (all private communications) that the researchers are in touch JDRF to discuss the funding of future studies. They may well be in contact with other organizations, I hope that they are, but I've gotten specific information about JDRF.
Not-So-Good News Second
It does not look like this is the kind of treatment that the FDA is likely to allow under the "surgical exception" that I discussed in the previous discussion of this research. So therefore, it is likely that a full FDA approval cycle will be needed, so about 4 clinical trials (and I'm not sure if this first one would count [d1]).
I do not think that any of the patients were ever free of injected insulin. So I don't think they cured anyone, even temporarily. On the other hand, I got the feeling everyone was helped to some degree. In some research, there are some people where it just doesn't work. Those people are sometimes called 'non-responders" and I think there were few to none "non-responders" in this trial.
The research below was all done in mice so I have not read it in detail, but it is listed, for people who want a lot more details.
http://www.sciencedirect.com/science/article/pii/S1568997210001795 (Cord Blood Background 2010)
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0004226 (Mice Cure 2009)
http://www.sciencedirect.com/science/article/pii/S0006291X07012715 (Beta Cells from Blood 2007)
http://www.sciencedirect.com/science/article/pii/S0014482706001558 (Why Stem Cells 2006)
Discussion and References
[d1] Unfortunately, the FDA doesn't give much weight to data from foreign trials, so things learned in other countries need to be relearned in the US, so the FDA will fully consider it. I'm quite worried that even once the study starts in the US, they might be limited to a very small phase-I study, because the FDA will not consider the Chinese study as proof of safety, even it if involves more people than an American phase-I study.
One of the researchers involved told me a story -- equal parts funny and shocking -- about trying to get approval for a medical device that had been tested in Australia. The FDA would not accept data from Australia. They wanted studies re-done in the US, so they could review that data, as though Australia was some corruption ridden, third world country, without a quality regulatory system!
[d2] Although I'm not sure exactly which proteins they are referring to, the general idea that a protein could re-educate the immune system is not controversial. Drugs like DiaPep277 and other antigen specific treatments are based on this idea. Haller's work in Florida is based on similar ideas, although his effectiveness was no where near what Zhao and crew see.
[d3] Although this idea was controversial a few years ago, I think that consensus is shifting. There is now some research that shows that stem cells already in the pancreas may be able to grow into beta cells. Even stronger was a paper published last year (sorry don't have the reference handy) which showed very specifically that in mice, alpha cells in the pancreas could turn into beta cells that produced insulin in response to sugar. Plus there is the Joslin "Medalist" study (more than one) and Dr. Faustman's paper just published last week which adds support to this same idea.
[d4] This was based on their own previous work in mice. But I know that other researchers have been looking into this area. Although the research in mice is not conclusive, there is some supporting evidence for this, in addition to the Zhao group.
All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My blog contains a more complete non-conflict of interest statement.
Clinical Trials Blog: http://cureresearch4type1diabetes.blogspot.com
Cured in Mice Blog: http://t1dcuredinmice.blogspot.com/