Other attributes
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by differences in social communication, deficits in social interactions, and restricted, repetitive patterns of behavior and interests. Individuals with ASD also display differences in reactions to sensory stimuli. Within the autism spectrum there is a great amount of heterogeneity, especially in terms of language and intelligence. Some individuals with ASD have no functional language and severe developmental delay while others have milder learning difficulties and some have average or above language skills and IQ.
The American Psychiatric Association changed the term autism to autism spectrum disorder in 2013. ASD is an umbrella term that includes Autistic disorder, pervasive developmental disorder – not otherwise specified (PDD-NOS), and Asperger syndrome.
ASD occurs in about one in fifty-four children, and boys are more likely than girls to be affected. Specific genetic causes for ASD can be identified in 10-20% of cases, which include genetic syndromes and rare changes in the genetic code. Environmental factors are thought to contribute to causing ASD. ASD risk factors include older parental age, low birth weight, prematurity, and maternal use of valproic acid or thalidomide during pregnancy. When one child in a family is diagnosed with ASD, the next child to be born has about a 20% grater risk of developing autism.
The early signs of ASD include the following:
- Child not responding to their name
- Child does not smile widely or show joyful expressions by the age of six months
- Lack of back-and-forth gestures, such as showing, pointing, reaching, or waving by twelve months
- No words by sixteen months
- No meaningful, two-word phrases by twenty-four months
- Loss of speech, babbling, or social skills at any age
Behavioral observation is the method of diagnosing ASD. Specifically trained health care providers, such as physicians, psychologists, and speech-language pathologists, do screenings and evaluations and may ask parents or teachers to record observations. Two of the leading autism diagnostic tools are DSM-5 (Diagnostic and statistical manual of mental disorders, 5th edition) and M-CHAT (Modified Checklist for Autism in Toddlers). Early interventions can reduce the severity of ASD. As of 2021, there are no FDA approved blood tests or biomarkers to diagnose ASD.
Neurodiversity is a framework adopted by many people with autism, particularly those with good language abilities and that can self-advocate. The neurodiversity view of autism includes the term neurotypical to the majority brain and sees autism as an example of a diversity of neurotypes among possible diverse brains. From this perspective, the severity of the disability depends on the environment the person is in. Disabilities can be minimized, and other traits may allow individuals to excel in more autism-friendly environments. Proponents of the neurodiversity concept do not treat autism as something to be cured and prevented. The more medical model of autism does aim to cure or prevent autism and is more supported by parents of ASD children who struggle in any environment, have little language, severe learning difficulties and other symptoms on the more severe end of ASD.
ASD treatments include behavioral interventions and therapies that teach new skills and address core deficits and symptoms. Treatment plans are individualized to the specific needs of the individual. Many people with ASD have additional medical conditions, such as gastrointestinal and feeding issues, seizures, and sleep disturbances. Treatments for these additional conditions may include behavioral therapy, medications, or both. Certain symptoms of ASD, such as irritability and aggression, can be treated with medications.
- Risperidone and aripiprazole are FDA approved drugs for ASD—indicated for the symptom of irritability
Medications prescribed off-label are those being used for conditions not specified in the FDA approved packaging label. Physicians may prescribe a drug for any reason they deem medically appropriate. Many medications initially intended for a separate condition have subsequently been clinically evaluated or continue to be evaluated specifically for ASD. Medications used in clinical trials for ASD are options for off-label prescription.
- Clozapine is an antipsychotic used aggression and tantrums
- Haloperidol (antipsychotic)
- Sertraline (Zoloft, Pfizer/Roerig, and generics) is a selective serotonin reuptake inhibitor (SSRI) that has been studied for anxiety disorder associated with Asperger syndrome
- Oxytocin (Pitocin, Par Sterile Products, and generics) is an endogenous hormone with a role in lactation and parturition, as well as relationship formation and social functioning in both humans and animals; oxytocin intranasal spray has been investigated for ASD
- Methylphenidate (Ritalin, Novartis; Concerta, Janssen; and generics) is a mild CNS stimulant indicated for attention-deficit disorders and narcolepsy
- Venlafaxine (Effexor, Pfizer/Wyeth, and generics) is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of major depressive disorder, generalized anxiety disorder, social anxiety disorder, and panic disorder; it shows evidence that it can improve self-injurious behavior and ADHD-like symptoms
- Bumetanide (generics) can lower chloride levels and shift GABA from excitation toward inhibition, areas affected by ASD and some clinical studies show benefit
- Rivastigmine, the acetylcholinesterase inhibitor (Exelon, Novartis, and generics) is indicated for the treatment of mild-to-moderate dementia of the Alzheimer’s type and mild-to-moderate dementia associated with Parkinson’s disease; studies in ASD showed improvements in cognition
- Mirtazapine (Remeron, Merck, and generics) is an oral tetracyclic antidepressant that enhances central noradrenergic and serotonergic activity that has been investigated for treating insomnia in ASD and other developmental disorders
- Melatonin for insomnia
- Arbaclofen is an investigational drug used to decrease spasticity related to multiple sclerosis (MS) as well as to improve social function and behavior in fragile X syndrome and symptoms of ASD such as noisy brain; The Simons Foundation purchased the patent to arbaclofen, and is sponsoring research into its use
Research on genetic disorders and syndromes, in which ASD is part of the disease profile is expected to give insights into the factors that lead to ASD. Genetic disorders associated with ASD include the following:
- Tuberous sclerosis complex (TSC)
- Fragile X Syndrome
- Phelan-McDermid Syndrome (SHANK3 gene)
- Rett syndrome
- PTEN gene mutations
Gene variants that could play a role in development of ASD is an active area of research. In an analysis of DNA from 35,584 people worldwide, including 11,986 individuals with autism, 102 genes were linked with an increased probability of developing ASD.
Neuronal synapses, the sites of communication between neurons are thought to have impaired function in ASD and neurodevelopmental disorders.
Brain imaging studies compare brain connectivity between people with and without ASD to identify differences specific to ASD which might represent points where therapeutic interventions might help.
Unique changes in mitochondrial metabolism are associated with ASD, such as elevated respiration rates and morphological alterations. About 30-50% of individuals with ASD have biomarkers of abnormal mitochondrial function and 80% of children with ASD may have abnormal electron transport chain activity in immune cells. Toxicants and nutrients associated with ASD risk can affect mitochondrial respiration. There are symptoms in common between ASD and mitochondrial diseases and classical mitochondrial diseases have an approximate 5% prevalence among people with ASD. Electron transport chain activity differences were found in fibroblasts from ASD individuals.
A link between imbalances in the gut biome and ASD have been found. Microbiota transfer therapy (MTT) is being investigated as a treatment for ASD, and this has been shown to improve gastrointestinal issues as well as other symptoms. MTT consists of treatment with the antibiotic vancomycin followed by a bowel cleanse and then high dose fecal microbiota transplant (FMT).
Auditory brainstem response (ABR) hearing tests may be a useful to diagnose ASD as slower brain responses to ABR tests conducted at birth were found in infants later diagnosed with ASD.
Metabolomics is the analysis of metabolites in a biological sample. Metabotyping is categorizing based on shared metabolic phenotypes that are identified using metabolic markers. Data from the Children’s Autism Metabolome Project (CAMP) was used to find metabotypes associated with autism in 357 children aged 18-48 months. The metabotypes were optimized and used in screening tests that detected autism in 53% of the participants in the CAMP study.
Major industry players include Pfizer Inc., Allergan, Eli Lilly and Company, Saniona AB, Merck & CO Inc., Consern Pharma Private Limited, Teva Pharmaceutical Industries Ltd., Novartis AG, Bristol-Myers Squibb and Otsuka Holdings Co., Ltd., Johnson & Johnson Services, Inc., Coronis Partners Ltd., Heptares Therapeutics Limited, Curemark LLC, Intra-Cellular Therapies Inc.
Cognoa is a California-based company that received FDA approval for its diagnostic tool that uses artificial intelligence (AI). The tool is delivered through a smartphone app and the assessment results are based on videos of the child and questionnaires filled out by parents and the pediatrician. The pediatrician uses the results from the algorithm, which was trained on data from hundreds of cases across gender, race and ethnic background, to make the diagnosis.
Autism Diagnostic Technologies is a New York-based company that developed a method of mapping brains and comparing non-autistic brains to autistic brains using MRI scan equipment. The technique was reported to predict which high-risk children would develop autism by age 2 with 80% accuracy using MRI brain scans performed at 6 months to 1 year. Enlargements of specific regions of the brain and changes in brain volume, surface area and thickness were features that predicted autism.
Behavior Imaging Solutions (BIS) is an Idaho-based company that created the remote autism assessment tool, Naturalistic Observation Diagnostic Assessment (NODA). The tool involves smartphone video capture and questions. The uploaded information is connected to an autism specialist. The assessment tool can shorten the wait time to diagnosis.
Linus Biotechnology is a New York-based company that developed the StrandDx-ASD assessment tool which uses molecular biomarkers. The biomarkers were developed at Linus Biotechnology using their exposome and biological response sequencing platform, also known as environmental biodynamics platform, that makes an assessment from a single strand of hair. The diagnostic aid received Breakthrough Device for Autism Spectrum Disorder (ASD) from the US FDA Center for Devices and Radiological Health in 2021. The device can be used to assess likelihood of ASD in children from birth to 18 months of age and aid in diagnosis for those 18 month to 21 years old. The exposome is a cumulative measure of environmental influences and biological responses over the lifespan.
BioROSA is a San Francisco-based company developing a blood test to detect ASD in children from the age of 18 months. The company is using computer algorithms to measure blood biomarkers and provide a risk score for ASD.
Cogniable is a company based in India that develops AI products for the early detection and management of ASD. It is developing an AI-based app that analyzes videos of guided play sessions.
AI-based robotic playmates that detect and classify factors such as eye-gaze and movement is an area being researched.
JelikaLite received FDA breakthrough device designation for its Cognilim System, designed to reduce symptoms of moderate to severe ASD in children aged 2 to 6 years. The device uses LEDs in a noninvasive headband to deliver infrared light and stimulate the brain. JelikaLite stated that a study of 30 children with ASD were treated with the photobiomodulation therapy with EEG sensor, combined with an AI personalization platform resulted in improved communication and daily living skills.
Floreo is a company in Washington D.C. that developed a virtual reality (VR) platform that provides autism therapy to children. The company received an NIH Fast-Track grant in 2017 and venture capital investments totalling $6 million as of July 2021. Floreo’s platform is approved for Medicaid reimbursement in several states in the US. The company is partnered with Frist Center for Autism and Innovation at Vanderbilt University to expand to independent-living training for adults with ASD.
Akili Interactive, a digital therapeutics startup in Boston is making computer games as medical devices and announced plans to go public through a merger with Social Capital Suvretta Holdings Corp. I. Akili is expanding from ADHD to ASD, major depressive disorder, and multiple sclerosis. The deal is expected to net up to $412 million in gross cash proceeds, valuing the combined company at about $1 billion.
Yamo Pharmaceuticals is a New York-based company that has therapeutic L1-79 in Phase 2 clinical trials, which includes adolescent and young adult participants with ASD. L1-79 is a tyrosine hydroxylase inhibitor designed to treat the deficits in socialization and communication. The drug modulates the catecholaminergic pathways thought to be dysfunctional in ASD. The study also includes the Brief Observation of Social Communication Change (BOSCC), which measures improvements in core symptoms. L1-79 received fast track designation by the FDA in 2018.
PaxMedica is a New Jersey-based company that developed PAX-101 (IV suramin), an antipurinergic agent intended to reverse the effects of mitochondrial dysfunction and also reduce neuroinflammation; PAX-101 is in a Phase II clinical trial
Quris AI, based in Boston and Tel Aviv, Israel, is prepping a drug for Fragile X syndrome for clinical testing. Quris is funded by Welltech Ventures, iAngels, and GlenRock Capital. Quris uses Ai-powered miniaturized “patients-on-a-chip” to try to predict safety and efficacy of new drug candidates to avoid risks and costs associated with failed clinical trials. Quris is partnered with The New York Stem Cell Foundation.
Finch Therapeutics Group is a clinical-stage microbiome therapeutics company based in Sommerville, Massachusetts with patents for products to treat ASD.
US20120128683A1: Insulin, IGF-1, with multiple known adjuvant therapeutic agents, as well as other pharmaceutical, biochemical, nurticeuticals, and biological agents or compounds delivered through the olfactory mucosal region of the nose and external auditory meatus.
WO2016191356A1: therapeutic composition comprising a fecal microbe or a fecal microbiota preparation to the subject
US9662371B2: oxytocin or oxytocin analogs
Finch Therapeutics and jointly owned with, and exclusively licensed from, the Arizona Board of Regents on behalf of Arizona State University and the Regents of the University of Minnesota, U.S. Patent No. 11,202,808, donor-derived microbiota
Finch Therapeutics, U.S. Patent No. 11,207,356, donor-derived microbiota