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Alzheimer’s drug shows promise for social behavior in a subset of children with ASD
A medication originally developed to slow cognitive decline in Alzheimer's disease — memantine — may improve social communication and engagement for a specific subgroup of children with autism spectrum disorder (ASD). A recent randomized clinical trial led by researchers at Massachusetts General Hospital and Harvard University found encouraging signals when the drug was given at higher doses and targeted to patients with particular brain chemistry profiles.
Location of the cingulate cortex in the human brain. (Overbye et al., Dev. Cog. Neuro., 2019)
Study design and principal findings
The trial enrolled 33 children and adolescents aged 8 to 17 without intellectual disability. Participants were randomized to receive 20 mg of memantine daily or a placebo for 12 weeks. Overall, the full cohort did not show uniform benefit — echoing earlier research — but a clear pattern emerged when investigators stratified participants by glutamate levels in a socially relevant brain region, the pregenual anterior cingulate cortex (pgACC).
Approximately half of the participants had abnormally elevated glutamate in the pgACC. In those children, caregivers reported statistically and clinically meaningful improvements in communication, interpersonal interaction, and social engagement with memantine compared with placebo. Children without elevated pgACC glutamate did not show the same gains.
The authors emphasize that these results are preliminary: the trial was small and short-term, and larger trials are required to confirm efficacy and safety for pediatric populations.
Scientific background: glutamate, the pgACC, and memantine
Glutamate is the brain’s principal excitatory neurotransmitter and is essential for learning and synaptic plasticity. However, excess glutamate signaling can lead to excitotoxicity and disturbed neural processing. The pregenual anterior cingulate cortex (pgACC) is rich in glutamate receptors and plays a central role in social cognition, emotional awareness, and motivation — domains often affected in ASD.
Memantine acts as an NMDA receptor antagonist, modulating glutamate signaling and protecting neurons from excessive excitation. In neurodegenerative diseases, memantine can slow symptom progression by dampening pathological glutamatergic activity. The new trial suggests that a similar mechanism may ameliorate social symptoms in children whose pgACC glutamate is elevated.
Brain glutamate levels in the study were assessed using neuroimaging measures that can quantify neurotransmitter concentrations (e.g., magnetic resonance spectroscopy), enabling researchers to identify the subgroup most likely to benefit.
Implications and next steps
These findings highlight two key points for clinical research and precision medicine in autism:
- Heterogeneity matters: ASD encompasses diverse biological profiles, so treatments effective for one subgroup may not help others. Earlier trials that treated ASD as a single homogeneous group may have missed subgroup-specific benefits.
- Biomarker-guided therapy: Measuring brain glutamate could become a way to personalize treatment, minimizing unnecessary exposure for children unlikely to benefit.
The research team calls for larger, multi-site trials with longer follow-up, broader age ranges, and careful safety monitoring. If replicated, memantine could become an option for a substantial proportion of children with ASD who show elevated pgACC glutamate, potentially improving social outcomes with limited exposure for non-responders.
Conclusion
A small, targeted clinical trial suggests memantine may improve social communication and engagement in children with ASD who have elevated glutamate in the pgACC. These results reinforce the need for biomarker-driven approaches in autism research and underscore the disorder’s biological variability. Robust confirmation in larger studies will be essential before memantine can be recommended as a treatment option for pediatric ASD populations.
Source: sciencealert
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