Mark Twain once said that the reports of his death were grossly exaggerated. Twain's words certainly ring true for proponents of various autism theories and treatments. After years of studies of refuting thimerosal and vaccines as a cause of autism, this hypothesis is still not allowed to rest in peace and is kept alive by those who believe in it.
Another treatment, Secretin, which ten years ago was one of the flavors of the month as an autism remedy seemed to be in abeyance over the past couple of years or so. Recently ARI director, Steven Edelson, who took over after autism icon Bernard Rimland passed away has writen an editorial on ARI's website trying to revive interest in this treatment as a line of autism research: http://www.autism.com/treatable/drug/secretin_org.htm. As regular readers of autism's gadfly will remember, I posted about this a couple of postings ago.
I emailed Dr. Edelson and pointed out that I had responded to his editorial, which the age of autism webpage had linked to. He seemed rather upset and felt that I had not been entirely honest or perhaps had not read the editorial carefully. He felt I should apologize to him and the readers of this blog.
Though I did not entirely agree with him he may have had some valid points. I said that he had stated that secretin was one of the most promising treatments ever. He said that he only felt that more research needed to be done to see whether or not this would be an effective treatment. Though the title of his editorial inferred that secretin was a promising treatment. He said that it had the potential to be one of the most effective treatments for autism without using the word 'ever' This did confuse me and maybe I was mistaken about that, but he did seem to me to think that there was more than just a need to do research and this might be a viable treatment. I also commented on Janet Kern whom he had stated had shown evidence that secretin was an effective treatment for autism. I had discovered that she had collaborated with James Adams, a member of the board of directors of ARI and she might have a connection with Edelson. He seemed to think I was implying something dishonest was afoot. He did admit to me that ARI had funded at least one study that Kern had done and that they had every right to do so. I agree. However, connections between a funder and a fundee need to be known as the parties may not necessarily be disinterested parties, this is just my opinion. I don't know what Dr. Kern's interest, financial and otherwise at the current time might be in Secretin or who else if anyone besides ARI funds her research. However, one thing I was able to find on the internet was that according to journalist Arthur Allen, Victoria Beck (the person whose son was the first anecdotal report of a person helped by secretin) and Bernard Rimland sold the patent for secretin to the drug company Repligen, who was first seeking out FDA approval for its use in treatment of autism and schizophrenia for one million dollars and about $700,000 of this went into ARI's coffers: http://www.salon.com/health/log/1999/12/09/secretin/print.html this same article states that after the one company that manufactured porcine secretin stopped producing it supplies dried up and secretin was being sold at prices as high as $15,000/vial. ARI does have the right to fund whom they want, I agree and Dr. Kern's findings have been published in the journal of autism and developmental disorders where the interested reader can judge for themselves the validity of her findings. I will have more to say about her findings later and I will apologize if there was any misunderstanding. Still, this is not the end of the story. There is still more stuff about this controversial substance.
Another thing I did not understand in the last post was that Steve was commenting on the fact that most if not all of the multiple studies that had refuted the evidence of secretin as a promising autism treatment had only used one dose of secretin and there was a need for more multiple dose studies before the final verdict on secretin was in. This was in addition to his statement that porcine (organic secretin extracted from pig intestines) was different chemically than the human synthetic secretin that was used in some though not all of the studies that refuted secretin.
I found one article and an abstract of another article on the internet in which multiple doses of secretin were administered: http://pediatrics.aappublications.org/cgi/content/full/107/5/e71
As far as I could tell Steve had not read these articles. He said that he would try to go to the research library the following morning and write an updated editorial for ARI and let me read it first. I still have not heard back from him. He also told me about someone named Cindy Schneider who had done a study showing that in a higher dose than usually given secretin had shown some results in persons with autism. As far as I could tell, from looking at the web, back issues of ARI's newsletter on the web and doing a pubmed search, this lady had never actually published her findings in a peer reviewed journal but rather had just presented them informally at a conference. If Steve or someone else will ever show me where Cindy Schneider has published in a peer reviewed journal, I will write an update.
I decided to do a bit more research. I read the article by Sandler which appeared in NEJM many years ago, He did acknowledge that his study used synthetic secretin rather than porcine secretin and the fact he only used a single dose, and that further work was needed to elucidate this. On doing my research I found that there had been studies by someone named Crist which appeared in a GI journal showing that the two different secretins have similar modes of action and effects in the body in spite of the fact that they have slightly different molecular structures, differing by two amino acids. It was conceded that this difference in molecular structure might mean they had different effects, but there was no evidence to show this.
One of the problems I have with the single dose thing is that the anecdotal reports of Parker Beck's improvement, the uncontrolled study involving three children published by Horvath, and Janet Kern's study showing improvement in a small percentage of the children in her study all involved a single dose of secretin. Therefore, this might preclude the argument that research with more than one dose of secretin is necessary. There have been studies showing secretin in mutliple doses is inefficacious, but more on that later.
In Kern's study the only children for whom secretin seemed to have any benefit were for those who had chronic diarrhea. What percentage of kids with autism who have chronic diarrhea is unknown. In one study, Karin Nelson even refuted that there was any relationship between GI symptoms and autism. Though, I think there are other studies that refute that. Apparently the relationship between autism and GI symptoms is not clear. Therefore, this would seem to dispute Steve's contention that secretin really has any potential for the vast majority of autistic persons. In his editorial he neglects to state that this might have potential only for a small subset of autism and in his comments on Kern's study, he does not mention the fact that the subset of children who had improved were unique in that they had chronic diarrhea and that Kern conceded secretin would only be helpful for a small percentage of those on the spectrum.
Also there was a report by someone named Sturmey who reported on the 15 controlled studies all of which had found secretin to be ineffective in the treatment of autism. I could not find this report on the shelves at the UCLA biomed library.
However I did find another report that had been published about a year earlier in 2004by Barbara Esch and James Carr on the research literature on secretin and autism. This was published in the Journal of Autism and Developmental Disorders. They talk about multidose secretin studies. In one of the studies done by Roberts which I think I linked to earlier, Steve E. claimed that the dosage was too low to get any positive results. He stated that Schneider, who I mentioned earlier had failed to get the same results from her work. But then got positive results after administering a higher dose, which was a single dose that Steve said he objected to before. As I mentioned before, I don't think Cindy Schneider's work has ever been published in a peer reviewed journal.
Also Sponheim et. al. have done a study involving multiple doses of secretin, I think I linked to the abstract of this study. These dosages were higher per kg of body weight than other studies involving secretin which would answer steve's concerns about dosages in the Roberts multidose secretin study.
Another issue that is addressed in this paper is that it is not known whether secretin crosses the blood-brain barrier in humans, though there is some suggestion that it might as there was a study showing it crossed the BB barrier in mice. However, if it were found that secretin did not cross the blood-brain barrier in humans this would probably negate its use as an autism treatment.
Another issue, that I mentioned in the previous post is that continued injections of porcine secretin may be dangerous because of an immunologic response to pig matter. Also, there is the question of those who promote multidose secretin as a treatment for autism, showing there is no danger. Secretin is currently used in single doses as an adjunct in GI procedures. I think this is the only use that has been approved by the FDA so far. It is not known whether multiple injections of even human synthetic secretin would not be dangerous to autistic children.
For these reasons I think caution should be exercised.
Though Steve seems to be implying that more research is needed to determine whether or not secretin is effective, i am not sure if he feels that way about the DAN protocol. If any of the DAN protocol (aside from the megavitamins which I think were published in some places) has been published in the peer reviewed literature, I am not sure what it is. Steve claims that 20% of all autistics that undergo the DAN protocol can become recovered. He uses the analogy of someone being hit by a car, and then undergoing physical therapy, and then just maybe walking with a slight limp so that you would never know they had an accident. He says that this is different from a cure, but seems to imply that these 20% responders can function pretty much normally in any way though may have some subtle differences.
I don't think any studies on secretin have been published in the past few years. If Steve can stop interest from waning and ARI or someone else funds more studies I will await the results. Though it does not seem to me based on what has been published that secretin has any promise whatsoever. As said before, there is certainly no evidence suggesting it has promise for any autistic person other than those who have chronic diarrhea.
There may be more updates in autism's gadfly about the fascinating saga of secretin so stay tuned.