The IQSEC2 protein is a guanine nucleotide exchange factor for Arf6.  Pathogenic variants in the X-linked IQSEC2 gene are associated with drug-resistant epilepsy, severe intellectual disability, and autism.  The vast majority of disease-causing variants introduce premature termination codons in the IQSEC2 gene, resulting in little or no IQSEC2 protein being produced.   We sought to determine if an adeno-associated virus (AAV) containing the IQSEC2 gene could rescue abnormal phenotypes in mice in two different Iqsec2 mouse models with premature Iqsec2 termination codons resulting in a knockout of Iqsec2 gene expression and in mice with a A350V Iqsec2 missense mutation.  In Iqsec2 knockout mice, the AAV significantly improved growth, corrected behavioral abnormalities, and normalized the seizure threshold.  We propose that success in the Iqsec2 knockout mice warrants a proof-of-concept study for gene replacement therapy in boys with IQSEC2 premature termination variants.

This is a joint presentation with the World Autism Organisation.

Originally published March 18, 2026

“By looking at the history of how ASD has been perceived and studied, it can be used to understand the source of biases and attitudes that individuals with ASD and their families endure by society. Often these perceptions are outdated, such as autism being caused by parents being neglectful, so condensing this information of disproven myths into its own webinar may be helpful in dispelling public misconceptions towards autism.”

— Helena Nguyen, Clinical Intern at The Johnson Center for Child Health and Development

This is a joint presentation with the World Autism Organization.

In this webinar:

1:00 – 12:00 – Organization and speaker introductions
13:00 – Early descriptions of autism
17:42 – Misconceptions and shifting paradigms
22:21 – Emergence of diverse research and advocacy
30:16 – Genetic and sensory insights, nutritional interventions
33:12 – Evolving diagnostic criteria and brain differences
41:00 – Biology, co-occurring conditions, and ABA certification
48:00 – Genetics, Neurology, and Comprehensive Lifespan Support
51:00 – Q&A

In this webinar, Dr. Stephen M. Edelson, Chief Science Officer for ARI, outlines historic milestones in autism research, understanding, and acceptance. He contextualizes pivotal studies and cultural references, highlighting their role in the evolution of autism understanding and acceptance. He summarizes nearly 100 years of autism research as follows:

Early descriptions of autism (1925-1940s)

The first documented study of autistic behaviors was published in 1925 by Ukranian researcher Grunya Sukhareva. Her pioneering work, though unrecognized for decades, laid the foundation for understanding diverse presentations of autism. Nearly 20 years later, Dr. Leo Kanner published a detailed description of 11 clinical cases instrumental in creating early diagnostic criteria. His work provided the first comprehensive description of autism and is still frequently cited today. A third contributor to early autism descriptions was Dr. Hans Asperger, whose work contributed to the recognition of “higher-functioning” presentations of autism (13:26).  

Misconceptions and shifting paradigms (1950s)

In the late 1950s, Bruno Bettelheim’s “refrigerator mother” theory falsely blamed parents for autism due to emotional neglect, causing immense guilt and hindering effective interventions. This harmful theory persisted until Dr. Bernard Rimland’s 1964 book Infantile Autism persuasively argued a biological basis for autism. His work asserts genetic, neurological, and environmental factors play a role in the development and presentation of autism. Rimland’s publication was a pivotal turning point in autism research as it successfully challenged prevailing psychological theories and redirected the discourse to the biomedical track. In 1967, Dr. Rimland founded the Autism Research Institute (ARI), creating a platform for funding and promoting biomedical research. Rimland also co-produced a documentary called “The Invisible Wall” to raise awareness (17:42).

Emergence of diverse research and advocacy (1960s)

The 1960s saw the emergence of multi-disciplinary investigations, with UCLA researchers like Edward Ritvo breaking into the medical aspects of autism, which marked the beginning of pharmacological research. Simultaneously, Ivar Lovaas was pioneering behavior therapy, which later developed into applied behavior analysis (ABA). Victor Lotter conducted the first prevalence surveys, estimating 4.5 in 10,000, providing a baseline for epidemiological studies. Cognitive theories from Uta Frith, Neil O’Connor, and Bette Hermelin emerged to explain distinct processing styles, laying the groundwork for our modern understanding of sensory differences in the autistic experience.

 During this time, diagnostic efforts also evolved, as Eleanor Mildred Creak’s British Working Group developed a nine-point diagnostic criteria in 1961. This was quickly followed by Lorna Wing’s “Triad of Impairment, which became a highly influential model for conceptualizing autism and directly impacted diagnostic manuals like the DSM and ICD. Parent advocacy also gained momentum, as Drs. Ruth Sullivan and Rimland established the National Society for Autistic Children (later Autism Society) in the U.S. and Helen Allison created its counterpart in the UK to empower parents and provide crucial support (22:21).

Genetic and Sensory Insights, Nutritional Interventions (1970s)

The 1970s brought significant insights, with Susan Folstein and Michael Rutter’s landmark twin study providing the first empirical data supporting a genetic component to autism, thus solidifying its biological basis. Concurrently, Jean Ayres pioneered sensory integration work, drawing attention to sensory processing differences and influencing occupational therapy interventions. Dr.  Rimland also explored the role of nutritional supplements like vitamin B6 and magnesium based on anecdotal reports from parents, highlighting the potential for biomedical interventions and individualized treatment approaches (30:26).

Evolving Diagnostic Criteria and Brain Differences (1980s)

In 1980, the DSM-III (1980) established “infantile autism” as a distinct category, which was a crucial step in formalizing the diagnosis. The 1980s also saw foundational neurobiological discoveries, as Margaret Bauman and Thomas Kemper documented the first evidence of neurological differences in the brain tissue of an individual with autism; thus validating its biological underpinnings (33:12). 

 Ivar Lovaas’s “The Me Book” democratized access to behavioral intervention strategies, and his recovery study, though controversial, fueled optimism and investment in early intensive behavioral interventions. This decade also saw public awareness surge as Temple Grandin’s autobiographical works offered unique insights into the autistic experience and challenged common stereotypes. The movie Rain Man also significantly increased public awareness, though in some cases it presents a limited view of autistic capabilities (37:06). 

Biology, co-occurring conditions, and ABA certification (1990s)

The 1990s saw a strong emphasis on the underlying biology of autism. The Defeat Autism Now (DAN!) movement brought co-occurring medical conditions, such as immune and gastrointestinal issues, into the limelight, advocating for their recognition and treatment as integral aspects of autism. Concurrently, Cure Autism Now (CAN) was established to fund biological treatments and prevention and find a cure for autism; this organization merged with Autism Speaks in 2005 and is currently the largest entity focused on autism awareness and support. Beyond medical interventions, various groups, including Families for Early Autism Treatment (FEAT), were established to support and advocate for early interventions. FEAT published the first autism e-newsletter, expanding information dissemination across the community. The Behavior Analyst Certification Board (BACB) was also created in the 90s. The BACB standardized the certification process for individuals offering Applied Behavior Analysis (ABA) (41:00).

Genetics, Neurology, and Comprehensive Lifespan Support (The 2000s – Now)

Profound advancements across several domains have characterized the period from the 2000s to now. Genetics research has exploded, moving beyond fundamental DNA analysis to include exome sequencing and epigenetics, with findings suggesting environmental factors like proximity to pesticides might increase autism likelihood. In neurology, increased focus on brain tissues, brainwave activity, advanced imaging, and neurotransmitters has deepened our understanding of the autistic brain. Recognition of co-occurring medical conditions has also expanded to include gastrointestinal problems, immune dysregulation, metabolic disorders, sleep disturbances, anxiety, depression, and more. Models like the Early Start Denver Model and functional communication training have gained significant traction and support in behavioral intervention methods. Dr. Edelson notes a need for more attention on pivotal response training. 

Dr. Edelson explains how the adult autism field has gained traction over the last decade or so. Issues like housing, employment, recreation, and persistent medical issues must be addressed in this population. This growing focus on senior issues emphasizes the need for nursing staff and group homes to understand autistic behaviors, sensory differences, and anxieties in older adults to provide appropriate care (48:00).

Dean Alexander, Ph.D., discusses pica, the ingestion of non-food substances, which has received insufficient attention as a common, sometimes lethal, form of self-injurious behavior. He discusses the prevalence of pica in autistic individuals and the long-term health implications associated with pica behavior. The speaker details numerous case studies and highlights the need for multidisciplinary collaborative treatment strategies based on functional behavior assessments. Alexander describes available treatment strategies and presents the SMART acronym for treatment recommendations. e.

Handouts are available for download (PDF) HERE
Take the knowledge quiz for this presentation HERE

This is a joint presentation by ARI and the World Autism Organisation.

In this webinar: 

2:12 – What is pica
5:22 – Study: Soda can and rubber ball
8:00 – Challenges with behavioral treatments
13:00 – Sensory stimulation and pica
14:20 – Pica prevalence and impact
16:08 – Study: GI symptoms and pica
17:30 – Study: Autism, GI symptoms, and pica
19:00 – Study: Pica prevalence in autistic adults
25:25 – Pica as a phenotypic subgroup
26:30 – Studies: polyvisol, vivinex, iron supplements, zinc and antioxidant therapy
29:46 – Metabolic profiles and phenotypic subgroups
31:57 – Why nutritional interventions
34:04 – Comprehensive vitamin-mineral interventions
36:10 – Dietary changes
38:21 – Study: Homeopathic treatment
44:28 – SMART interventions

Pica and behavioral treatments

Pica is the ingestion of inedible substances and is the most dangerous form of self-injurious behavior associated with autism (2:12). Items frequently ingested include generally harmless things like dirt, leaves, and grass, as well as dangerous and potentially lethal items like rubber gloves, clothing tags, and screws (3:30). Alexander details a case study involving a 50-year-old autistic man who ingested cigarette butts. The presenter explains how treatment strategies capitalized on the individual’s preferences by incorporating soda cans and a red rubber ball into his walk to work. Over six months, the client’s nicotine and cotinine levels decreased from those of a chain smoker to zero (5:22). Alexander highlights the simplicity of this case, noting the trial and error implicit in creating holistic treatment strategies (6:43). 

Establishing effective behavioral treatments for pica can be challenging due to costs, availability, environmental restrictions, and the generality of treatments across time (8:00). The presenter notes the importance of functional behavioral assessments, which help identify the factors that drive and maintain pica behavior, like attention-seeking, sensory issues, pain attenuation, or escape/avoidance (11:00). Sensory stimulation, he continues, is often a significant factor in maintaining pica behavior and can be challenging to address. Solutions to sensory drivers can include finding substitute foods with similar sensory properties (i.e., grape nuts in place of dirt) or engaging individuals with play during unstructured hours (13:00). The presenter notes that pain attenuation is often related to dental issues (14:01). 

Pica Prevalence and Impact

Around 23.2% of autistic children and up to 60% of autistic adults experience pica (14:20). The speaker outlines two studies on the intersection of autism, pica, and GI issues in children (16:08). Researchers found that autistic children and children with developmental disorders who also have pica have a higher prevalence of GI signs, symptoms, and diseases compared to those without pica (15:24). Prevalence of food cravings and specific GI conditions like irritable bowel syndrome (IBS) and gastroesophageal reflux (GERD) are also higher in autistic children with pica than those without (17:30). To assess the prevalence and co-occurring conditions in adults, researchers examined ten years of medical records compared to a comprehensive list of symptoms and diseases (19:00). Four groups were assessed: autism only, autism and pica, pica without autism, and a control group of developmentally disabled individuals without pica. Findings revealed that the prevalence rates across the ten most frequently occurring diseases were two to three times higher for individuals with pica, where the autism and pica group had the highest rate (22:33). Alexander emphasizes that pica takes a severe toll on the body over time which can lead to shorter life expectancy and higher mortality rates. He asserts that autistic individuals with pica may represent a phenotypic subgroup characterized by GI symptoms and requiring specialized treatments (25:25). 

Intervention Options

Alexander outlines research showing that autistic children have relatively less diversity in gut bacteria and generally have fewer healthy bacteria than unhealthy (30:55). These findings emphasize the importance of including nutritional interventions in treating pica. The speaker underscores that dietary interventions do not necessarily rely upon practitioner availability and so may be more accessible (27:36). He details promising research using iron supplements, liquid multivitamins (poly-vi-sol), specialized formulations (vivinex) (26:30), and zinc supplements and antioxidant therapy (28:42) to reduce pica behaviors like coprophagy (ingestion of feces) in autistic individuals. The presenter discusses a study that revealed significant differences in metabolic profiles between autistic children and their non-autistic peers (29:46). Targeted nutritional therapies, including folinic acid, betaine, and methyl B12, succeeded in correcting metabolic imbalances. Alexander asserts these findings suggest the presence of a metabolic phenotype and that aspects of autism are treatable. 

Maintaining a healthy gut is critical for the body’s ability to fight infection, digest food and produce vitamins (31:57). The presenter outlines other nutritional treatment approaches, including gluten-free, casein-free, and Mediterranean diets (37:17), as well as comprehensive vitamin-mineral interventions (34:04). Alexander details a case study where a seven-year-olds pica behaviors stopped just one week after implementing a gluten/casein free diet (36:10). The speaker summarizes the behavioral, dietary, and vitamin/mineral based interventions and highlights the need to try and assess each strategy. He outlines a homeopathic treatment study that showed remarkable improvements in a 15-year-old boy with severe autism. Supplemental behavioral interventions alongside homeopathic recommendations significantly improved the child’s functions, behavior, communication, and quality of life (38:21). 

S.M.A.R.T. Interventions

Alexander highlights the need for collaborative treatment strategies and introduces the SMART acronym for treatment recommendations (44:28): 

Safety: Safety precautions are critical. Potential dangers and treatment environments must be appropriately assessed based on individual needs.

Medical issues related to eating habits, food cravings, stomach pain, antibiotic use, and mouth sensitivities must be addressed. It is best to be assessed by a team of professionals including, but not limited to, a dentist, GI specialists, and nutritionist (45:33). 

Analysis/assessments of behavior function and consequences are best practices. Such assessments are critical for accurately identifying drivers and potential treatments for pica behavior (47:40). 

Reinforcement inventory or a “menu” of activities or objects that help minimize Pica behavior (e.g., soda cans and rubber balls). These can aid in implementing differential reinforcement strategies and finding alternatives. 

Treatment packages or a combination of various approaches to create a collaborative treatment strategy. Treatment packages include psychotherapy, pharmacological treatments, behavioral techniques, and nutritional support. Such holistic therapies are generally the most effective (49:44). 

Dean Alexander, Ph.D., discusses pica, the ingestion of non-food substances, which has received insufficient attention as a common, sometimes lethal, form of self-injurious behavior. Behavioral approaches to treatment, more often than not, fall short. Biological intervention, if supported, may hold out new promise.

Handouts are available for download (PDF) HERE

This is a joint presentation by ARI and the World Autism Organisation.