Autism Spectrum Disorder

Summary — The most systematic stem cell research in autism spectrum disorder has been carried out by a team at Duke University in the United States. A phase I study using banked cord blood confirmed safety and feasibility, and a randomised, placebo-controlled phase II study of 180 children found no difference between groups on its primary outcome, although exploratory signals were reported in some subgroups. A phase I study of cord tissue-derived mesenchymal stromal cells has also been carried out.

What is autism spectrum disorder?

Autism spectrum disorder is a neurodevelopmental condition characterised by difficulties with social communication and interaction, restricted and repetitive behaviours or interests, and differences in sensory sensitivity. Features usually begin to appear in early childhood, and their degree and pattern vary so much between people that the term 'spectrum' is used. Some children are late to develop language, while others have strong language skills but find social situations hard to read; intellectual disability, epilepsy, sleep problems and gastrointestinal symptoms may also occur.

No single cause explains it. Twin and family studies show that genetic factors play a large role, with many genes each contributing a small effect, and some studies suggest that environmental factors during pregnancy may also contribute. Some researchers have noted changes in immune- and inflammation-related markers in the brain and blood of autistic people, and this became one background to stem cell research.

Current standard support

There is currently no medicine that changes the core features of autism spectrum disorder. Early identification together with behavioural and developmental interventions, speech therapy, occupational therapy, social skills training and parent education are central, and medicines may be used for co-occurring problems such as irritability or sleep difficulties. These interventions usually continue over the long term, tailored to the child's stage and characteristics. Stem cell research does not aim to replace this support but to test whether something could add to it.

Why stem cells are studied

Researchers proposed two main hypotheses. First, factors secreted by cord blood cells or mesenchymal stem cells might modulate immune and inflammatory responses in the body and brain. Second, this modulation might indirectly influence the connections or function of brain networks. These hypotheses come from animal studies and research in other neurological conditions; they are different from the idea that infused cells turn into brain cells. How the cells act in people, if at all, has not been established.

Cells used and how they were given

• Autologous cord blood — the child's own cord blood, banked by the family at birth. Rejection is less of a concern, but only children with banked cord blood can take part.
• Allogeneic cord blood — partially matched donor cord blood, used in the phase II study for children without their own banked units.
• Cord tissue-derived mesenchymal stromal cells — cells grown from donated umbilical cord tissue, which can be produced in quantity to a consistent standard.

All three were mostly given by intravenous infusion, once or a few times, followed by several months to a year of observation.

Reported research findings

① Open-label phase I study of autologous cord blood (2017) — the Duke team gave a single intravenous infusion of their own cord blood to 25 young children with autism spectrum disorder. The main aim was to confirm that the procedure was safe and feasible, and infusions were reported to have been given without serious safety problems. The investigators also reported changes in social and communication measures on parent ratings and clinician observation, but made clear that without a control group they could not tell whether these changes were due to the infusion, to behavioural interventions received at the same time, or to natural development.

② Randomised, placebo-controlled phase II study (2020) — building on phase I, the team studied 180 children aged 2–7. Children were randomised to cord blood (autologous or allogeneic) or placebo, and socialisation scores were compared after six months. Across the whole group there was no statistically significant difference on the primary outcome. In an exploratory analysis limited to children without intellectual disability, differences were reported in some communication measures and EEG measures. The investigators explained that these findings generate hypotheses and need confirmation in a separate study.

③ Phase I study of cord tissue-derived mesenchymal stromal cells (2020) — the same team gave allogeneic cord tissue-derived mesenchymal stromal cells at different doses to 12 children. The aim was to establish safety and an appropriate dose, and most reported adverse events were mild to moderate. These results are being used to design later-stage studies.

What has been reported about safety

These studies reported mild-to-moderate adverse events such as transient reactions related to infusion or symptoms of infection, and serious safety problems during the study periods were described as uncommon. However, participant numbers were small and follow-up was not long, so long-term safety is not yet well known. It should also be remembered that in research settings cell quality control, monitoring before and after infusion and emergency preparedness were strictly managed.

Open questions

Because autism spectrum disorder is so varied, studies are needed that look precisely at which changes occur in children with which characteristics. Remaining tasks include re-testing the subgroup signals from the phase II study in pre-planned randomised studies, clarifying mechanisms, and determining the right cell type, dose and number of infusions. The International Society for Stem Cell Research (ISSCR) states that such confirmation should come through rigorous clinical trials and independent review.

The above summarises results reported in published papers and public-agency materials. University and institute names are given to identify research sources, not to introduce or recommend any medical institution. Reported results do not mean the same effect for everyone, and the suitability of any treatment is decided by the medical team.

Autism, Developmental Disorders & Cerebral Palsy →