In a groundbreaking study, researchers at Mass General Brigham have discovered that memantine, a drug traditionally used to treat Alzheimer’s disease, may significantly improve social functioning in young individuals with autism spectrum disorder (ASD) who do not have intellectual disabilities. The study, published in JAMA Network Open, highlights the potential of memantine to address social impairments in this population, particularly among those with elevated levels of glutamate, a key neuron-activating chemical in the brain.
The randomized clinical trial involved 42 participants aged 8 to 18, and its findings could pave the way for more targeted treatments for ASD. The research revealed that participants with high glutamate levels in the pregenual anterior cingulate cortex (pgACC) responded more favorably to memantine, suggesting that measuring glutamate levels could help identify individuals most likely to benefit from this treatment.
Understanding the Role of Glutamate in Autism
Autism spectrum disorder affects over 2% of children and is characterized by challenges in social interactions and communication. Previous research into glutamate-modulating treatments, including memantine, has yielded mixed results. However, the current study builds on earlier findings that optimal doses of memantine can produce promising outcomes in adults with ASD.
Dr. Gagan Joshi, the study’s corresponding author and director of the Bressler Program for Autism Spectrum Disorder at Massachusetts General Hospital, explained the rationale behind the research. “If you have elevated blood glucose, we prescribe antidiabetic medications to decrease blood sugar levels. In the same way, we looked to see if glutamate modulators could improve social functioning in autism for individuals with abnormally high brain glutamate levels,” he said. “We saw that patients who responded to memantine became more socially engaged.”
Clinical Trial Insights and Outcomes
The federally funded study was a 12-week, randomized, controlled trial that included 42 participants with ASD, of whom 33 completed the trial. Sixteen participants received memantine, while 17 were given a placebo. Additionally, 37 participants with ASD and 16 healthy controls underwent brain scans to assess glutamate levels in the pgACC, a region associated with social processing and emotional awareness.
Memantine treatment was associated with a significantly higher rate of improvement in social behaviors (56%) compared to placebo (21%).
Although some participants reported mild side effects such as headaches, the treatment was generally well tolerated. Notably, 54% of the ASD participants had high glutamate levels in the pgACC, and 80% of these individuals responded favorably to memantine. This suggests that pgACC glutamate measurement could serve as a biomarker for identifying patients likely to benefit from memantine treatment.
Implications and Future Research
The study’s findings open new avenues for personalized treatment approaches in autism, emphasizing the importance of biochemical markers in predicting treatment responses. Dr. Joshi noted, “In our study, participants who responded to memantine showed improvements in social competence and a reduction in autism symptom severity, although they continued to experience milder features of autism.”
While the results are promising, larger clinical trials are necessary to evaluate memantine’s efficacy across a broader ASD population. Furthermore, additional research is needed to determine whether elevated glutamate levels can predict responses to other glutamate modulators, potentially offering more treatment options for those with ASD.
As the field of autism research continues to evolve, the potential of memantine and similar drugs to enhance social functioning represents a significant step forward. By identifying specific biomarkers, healthcare providers may be able to tailor interventions more effectively, improving the quality of life for individuals with autism and their families.