In most, but not all, cases of moderate to severe ASD, autism is a multifactorial, environmental triggered, immune mediated disease. To be clear I am speaking only about moderate to severe autism. HF ASD, what used to be called Aspergers, seems to be something else entirely.

OK, back to Dr. Jeste. To her credit she catalogued all the failed genetically driven clinical intervention trials. Suffice it to say it is a LONG list. Donepezil, Mavolgurant, Abacoflen....Let’s take a closer look at one of the biggest failures- Seaside Therapeutics.

Former AS Science Director, Dr. Rob Ring, was a diehard believer in the idea that we would soon be able to diagnosis and treat autism solely via genetic profiles. Ring eagerly invested over $2million of AS money (so easy to spend $ you did not earn!) into Seaside Therapeutics’ study on Fragile X/ ASD children. His predecessor, Dr. Geri Dawson was also an enthusiastic proponent of this venture. Neither Dawson nor Ring would listen to any fact based concerns, primarily that Fragile X was a poor autism research model. Ring was especially vehement that the study would succeed. A number of ASD parents tried to make Ring understand how different FX was to non syndromic (the other 90%) autism. Ring, having no experience teaching, treating or even interacting with autistic people, insisted that he knew better and that any FXS treatment would easily translate to to non genetic ASD.

Naturally, Ring and Dawson were completely wrong. The Seaside FXS project was a hugely expensive failure. Interestingly, the FX kids, did indeed, experience behavioral improvements. That makes sense because they were the treatment model! But Bac had no impact on non FX ASD.

Dr. Jeste spoke her clinical intervention failures using 22Q kids as ASD treatment models. Jeste seemed to believe that a bigger sample size would have yielded benefits. No! The idea of more of our tax $ going into this black hole is preposterous. Jeste did briefly mention that the fact that her studies enroll higher functioning, healthy, albeit with genetic disorders kids, may be part of the problem but she clearly believed the real stumbling block was the sample size.

I have been reading through a number of recently published papers on the failure of FXS research. Dr. Tim Chiang found that FXS kids have “very different speech, motor and development issues” than non FX ASD children.” L. Abbeduto’s research concluded that “the onset, symptomology, developmental trajectory between FXS and ASD differs in important ways.” Even more significantly, J. Roberts’ work concluded that “FXS has a unique neuro-endocrine profile,” so different from that of non FX and ASD children. Another important difference is the fact ASD people have high cortisol levels (the struggle with fight or flight), FXS children do not. Finally, if Jeste and others were to argue that these are fringe opinions, Dr. Thurman of the NIH has published numerous studies elucidating the problematic and significant differences between FXS and ASD.

NIH’s Dr. A. Thurman states: “ It has been assumed that ASD symptoms reflect the same underlying psychological and neurobiological impairments in FXS and ASD which has lead to the claim that targeted pharma treatments that are efficacious for the core symptoms of FXS will be beneficial to non FX ASD as well. Yet, neurobiological substrates of behavioral impairments represent important clinical differences...a more symptoms based, less syndromic (genetic) based approach is needed.”

Layman’s terms - FXS, 22Q, Tuberous Sclerosis etc...research will not help the other 9o% of people with ASD.

In the same vein as FX, it’s often cited that 50% of children with Tuberous Sclerosis have autism. TS is a very serious disease involving reoccurring brain tumors. Not surprisingly, TS children frequently suffer from epilepsy and have developmental delays. Rob Ring was insistent, as he was with FX, that a massive investment into TS “autism” would yield real “targeted treatments” for non TS ASD children. Well a decade and many millions of dollars later - nothing, nada, rien...Absolutely no success at all. While there are behavioral and biological overlaps, very, very few TS children meet the official criteria for autism.

Jeste spoke at length about doing EEG work on “ASD” 22q11 children. It has been commonly assumed that 50% of 22Q kids also have ASD. That never made sense to me. The 22Q kids I have meet seem positively happy! They do have significant development delays but always seemed social and have more in common with Downs syndrome kids than ASD children. In 2013 MIND researchers who used the 22Q “autistic” kids as ASD research samples started to ask questions. Dr. Tony Simon noticed that these “autistic” children “have a very high level of social motivation. They (22Q) get a lot of pleasure from social interaction and are socially skilled.” Tony administered the DSM ASD criteria test to each one of his 29 22Q “autistic” subjects and found NONE of them actually had autism. In another 22Q “autism” study researcher K. Angkustsiri re tested her 22Q subjects and found that none of those children meet official ASD criteria either. Indeed, it is obvious that 22Q is a very different disorder altogether, involving heart problems and serious malformations in the head.

Ok, so I think we know that problem with Dr. Jeste’s research is not that she needed a larger sample size of FXS or 22Q “autistic” subjects.

The second critical problem with Jeste’s research is her insistence that we will be able to phenotype ASD kids via EEG! I know, insane, right? If there are ASD Moms and Dads reading this they know what I mean. Despite incredibly kind and patient technicians, it was a torturous process getting my son’s EEG done. Autistic kids, by nature, do not enjoy being touched by strangers or held captive, prone on a table while electrodes are glued to their heads. My son, Christian, absolutely hated the feeling of the nodules on his head. The removal process was just as traumatic. Christian actually has epilepsy and still his 72 hr EEG was minimally remarkable. It is a crude tool unless you are administering a relatively complex test at the time of the EEG. Only HF ASD people would willingly be fitted with an EEG. And only HF ASD people could engage in a conversation while hooked up to an EEG. I think kids like mine would rather hug strangers on the street.

In order to demonstrate that the EEG was a easy tool to use on autistic subjects, De. Jeste shared a video of an autistic girl with an EEG cap on. The girl was smiling and looked so happy, skipping around with the equipment on her head. Indeed, Dr. Jeste said that this girl loved the process and loved the EEG equipment so much she kept it. Guess what? That “autistic” subject had 22Q! NO one with real moderate to severe ASD wants an EEG done, nevermind enjoy the process. How could the investigators make such obvious errors? Are they so wedded to belief that autism is primarily genetic that they refuse to see the obvious signs that most of “syndromic autism,” is not autism at all?

There was much discussion about how EEGs will leverage information about genetic etiologies - sure, but for kids who don’t have autism! So much is wrong with this stubbornly naive assumption. 1) FXS and 22Q “autism” research has been a tremendous failure for a reason- these children don’t have autism and 2) one cannot phenotype autism via genetic etiologies- that has been tried and tried for 20 years and failed. 3) autism is more than a neck up disorder! 4) It is 2018 we know in singleton autism (the most common kind) is 60% environmental in cause and 5) Two factors that are as important, if not more important than genetics (and 100% more actionable), in the phenotyping of autism are and autistic person’s micro biome and the immune system.

I am sure there are many children with genetic disorders who do indeed have DSM dx autism, just far fewer than we have been lead to believe. If I were a parent of a FX child who had some ASD features I would want the ASD dx to get more services for my child. I am all for ANY label that helps children get services. The only thing that needs to change is that researchers must stop using FX, 22Q, Tuberous Sclerosis kids as research templates for autism.

NIH’s Dr. Audrey Thurman is right. We are getting nowhere via the “syndromic autism” studies, symptoms orientated research is the way forward. We can’t waste more time. Most of our children are really struggling and often living with pain and/or life threatening conditions like intractable epilepsy. Research GI issues, GI treatment, the miracle seizure stopper Charlotte’s Web for epilepsy (vs. endless research into epilepsy genes), study the biology of regression (not just the behavioral aspects), study medical marijuana for severe self injurious behavior, study autoimmune interventions for regression and PANDAS, etc...In short help autistic people.

* Dr. Jeste is a behavioral child neurologist specializing in autism and related neurodevelopmental disorders. She is an Associate Professor in Psychiatry and Neurology in the UCLA David Geffen School of Medicine, and a lead investigator within UCLA Center for Autism Research and Treatment (CART). 

 Katie Wright is Contributing Editor to Age of Autism.