Wow, amazing interest in the article by Moises Velasquez-Manoff in yesterday’s Sunday NYT (link to it is found on my Facebook page). The title is provocative and the style is very flashy and not at all scholarly or scientific. He does not back up his claims with footnotes or cite the evidence for the claims in article – there are no data, tables or figures to support the case. But, this is a newspaper Opinion Piece, not a science writer’s blog. A newspaper would not put a scholarly article in the Opinion page of its Sunday edition! In fact, last fall I sent around a carefully worded, respectable piece, that made many of the same points as this article does, and it was rejected by all major newspapers I sent it to. I conclude that it takes a different style to get published in this type of venue, and Moises is good at this.
Style aside, the crucial importance of this article is that it gets the message of immune involvement in autism out there in the public eye. This is what I’m trying to do with this lowly blog, and with my book. Moises reached far more folks in one day than I have I’m sure. It’s the most emailed article of the week in the NYT.
But how accurate are his claims? Moises says in his third sentence (!) that “At least a subset of autism – perhaps one-third, and very likely more – looks like a type of inflammatory disease. and it begins in the womb.” The work of Tony Persico, which I highlighted in a July 18 post here, estimates that an immune-related cluster of symptoms is present in about 18% of his autism patient population. Carlos Pardo found evidence of an immune activated state (activated microglia and astrocytes, and strikingly elevated cytokines) in the brains of most of his postmortem autism cases. Several of the Pardo findings (see my 11/19/11 post for update, and my book for full story) have been reproduced by others at UCSD, UCDavis and here at Caltech. In addition, many studies have demonstrated immune abnormalities in the blood in autism (as we have shown in our mouse model of the maternal immune activation risk factor for autism). Moreover, as I’ve pointed out here before (and in the book in detail), there are several reliable studies showing that a high proportion of ASD kids have gastrointestinal problems, many of which could be related to inflammation, such as “leaky gut”, wherein the intestinal barrier allows large molecules to leak out into the circulation. So, I fully agree with Moises that there is a very significant proportion of ASD patients with immune-related problems. Whether it is a third or more than that, is open for debate and further research.
Does this immune dysregulated state “begin in the womb”? First, as Moises points out, there is strong evidence from a huge population of ASD cases in Denmark connecting maternal infection with elevated risk for ASD in the offspring. This is now replicated in a similar, large study in Sweden that was reported at the IMFAR meeting this spring. Additional evidence of this is provided by studies showing markers of inflammation in the amniotic fluid and maternal serum in cases where the offspring turned out to have ASD. A new paper from the Danish group now shows that newborns who go on to develop ASD have elevated serum cytokines. Evidence from our maternal immune activation mouse model is consistent with many of these findings, and our results also provide evidence that the immune dysregulation seen in the blood of adult offspring does begin in the embryo (see my 7/17/12 post here).
Moises then makes a connection between the rise in autism diagnosis, autoimmune disease in the mother, and the hygiene hypothesis, as I did in my book. It seems logical to me to connect the documented rise in autoimmune disease seen in industrialized countries – please see the figure in my June 27, 2012 post that illustrates the truly remarkable parallel between the rise in a number of autoimmune diseases and the fall of a number of infectious diseases. Since a number of studies have shown that autoimmune disease in the mother raises the risk for ASD in the offspring, it again seems logical to connect this with the rise in ASD diagnosis. This is still an hypothesis, of course, but it is based on logic.
In the last part of his article, Moises goes on to extend the hygiene hypothesis to parasites (worms in the GI tract) and notes that a clinical study will begin soon in NYC testing whether giving the parasite Trichuris suis to adult autism subjects will ameliorate their behavioral symptoms. As I’ve pointed out in previous posts here, the idea is that helminth worms can have anti-inflammatory effects, and they are, in an evolutionary sense, a “natural” treatment. The particular parasites to be used have been found to be seemingly harmless in prior human studies. I sincerely hope, however, that the patients to be entered into this study belong to the subset of autism cases that are “immune-related”, otherwise this treatment will likely not correct anything. It will also be important to test for the efficacy of this treatment in reducing immune abnormalities in the blood of the patients. It would also be very revealing to determine if the abnormal, possibly “bad” microbiota (clostridia, sutterela) that should be present in these preselected patients are replaced by “good” (lactobacillae) bacteria (see my post of Jan 19, 2012 on this). [Note: I looked up this trial on ClinicalTrials.gov and the protocol does not mention selecting patients who have immune dysregulation or GI problems, nor does it mention assaying immune parameters before and after treatment]
The one point Moises makes that I am unfamiliar with is about the lack of autism in Cambodia. I’ll have to try to track down a reference for that. Note: Moises just sent me the ref for this – it is a essentially a case report from a doc on Cambodia who is familiar with autism diagnosis and says that he sees remarkably few cases at his center. [Note: here is an update on ASD in developing countries in an article from Iran]
Importantly, Moises says that he is putting together an annotated version of his article that will go on line and show where he got his info from. Good!