Autism spectrum disorder

ASD is a spectrum of neurodevelopmental conditions ranging from severe forms with absent speech and profound cognitive deficits to high-functioning Asperger's syndrome. Modern neuroscience views autism as a condition with multifactorial pathophysiology: chronic neuroinflammation, imbalance of excitatory and inhibitory neurotransmitters, immune dysregulation, intestinal dysbiosis. According to the US CDC, the prevalence of ASD has reached 1:36 children. Standard therapy — behavioural methods (ABA), speech therapy, occupational therapy — yields results but does not address pathophysiological mechanisms. Cell therapy is regarded as a complementary modality that may amplify behavioural rehabilitation, particularly in children with the regressive form of ASD, in whom development proceeded normally until 1.5–2 years and previously acquired skills were subsequently lost.

Epidemiologically, the rise in ASD prevalence over the past two decades reflects both expansion of DSM-5 diagnostic criteria and a real increase in incidence. Twin studies indicate heritability on the order of 70–90%; more than 100 risk genes have been identified, most encoding synaptic proteins (SHANK3, NRXN1, NLGN3, MECP2). Beyond genetics, perinatal factors predispose to ASD: extreme prematurity, maternal infection during the first trimester, severe pre-eclampsia, and selected neonatal epileptic encephalopathies. The hypothesised link with vaccination, repeatedly tested in large epidemiological studies involving millions of children, has been refuted at the level of evidence-based medicine — we record this point for families who postpone therapy because of unfounded concerns.

At the neurobiological level, several reproducible abnormalities have been described in ASD. Post-mortem and neuroimaging studies show activated microglia and elevated pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ) in cortex, cerebellum, and subcortical structures. The excitation/inhibition (E/I) balance is disrupted — relative excess glutamatergic transmission against deficient GABAergic transmission. Structurally, atypical synaptogenesis is observed: an excess of synapses early in development followed by insufficient pruning during adolescence. This explains the coexistence of hypersensory reactions and difficulty processing social cues. In 30–60% of patients, peripheral markers of an autoimmune process are detectable — antibodies to neuronal proteins, increased CD8+ component, impaired regulatory T-cell function.

A separately important component is the gut–brain axis. Gastrointestinal symptoms are present in 30–50% of children with ASD: alternating constipation and diarrhoea, abdominal discomfort, restrictive eating. The microbiota in ASD shows a characteristic dysbiosis: depletion of protective Bifidobacterium and Lactobacillus, expansion of Clostridium species and producers of short-chain fatty acids, particularly propionate. Increased intestinal permeability ("leaky gut") allows lipopolysaccharide and bacterial metabolites to cross the barrier and act on neurons via systemic inflammation. This does not mean ASD is a disease of the gut, but it explains why systemic immunomodulation by mesenchymal stem cells can indirectly improve behaviour.

Standard ASD therapy is multilayered. Behavioural therapy under ABA protocols (Applied Behavior Analysis) at intensive levels (≥25 hours per week for 2–3 years) produces significant functional improvement in 30–50% of children, while the remainder respond weakly or not at all. Concurrently TEACCH, DIR/Floortime, ESDM, PECS, sensory integration and occupational therapy, speech therapy, and motor therapy are deployed. Of pharmacological agents, only two are FDA-approved for irritability and aggression in ASD — risperidone and aripiprazole; no medication modifies the core symptoms (communication and social interaction impairment). All these methods address manifestations rather than the underlying pathophysiology — chronic neuroinflammation and immune dysregulation.

Mesenchymal stem cell and exosome therapy in this context functions as a modifier of the biological background. Following intravenous administration, UC-MSCs switch activated microglia from a pro-inflammatory M1 to a regenerative M2 phenotype, lower systemic pro-inflammatory cytokines, restore regulatory T-cell function, and via humoral signalling influence the state of intestinal mucosa. Intrathecal administration delivers cells and their secretome directly to the CNS. Nasal exosomes are a separate delivery route bypassing the blood-brain barrier through the olfactory nerve; they may be used as a home course between procedures. In children with the regressive ASD phenotype, where neural networks were already established before skill loss, the effect is typically more pronounced; in classical non-regressive ASD the gain is more modest but reproducible — particularly in sleep, sensory regulation, and behavioural stability. The Hanshi United programme uses three procedures at 15–20 day intervals, mandatory continuation of ABA or an equivalent behavioural programme, and assessment by CARS, ATEC, and video-clinical material at baseline, 3, and 6 months. This separates real dynamics from natural development and parental placebo effect.