Could an Asthma Medication Promote Autistic Disorders?

Autism spectrum disorders affect about 1% of children worldwide, and their prevalence continues to rise. While genetic factors account for less than half of the cases, environmental causes remain poorly understood. A recent study reveals that a widely prescribed asthma medication, montelukast, may play an unsuspected role in the onset of autistic behaviors.

Montelukast works by blocking certain receptors involved in inflammatory reactions. However, researchers have discovered that it also disrupts retinoic acid signaling in neurons. Retinoic acid, derived from vitamin A, is essential for brain development, synapse formation, and the regulation of key biological processes such as neurogenesis. A deficiency or dysfunction in this signaling has already been linked to an increased risk of neurodevelopmental disorders.

Experiments conducted on rats showed that exposure to montelukast during pregnancy or shortly after birth led to behaviors similar to those observed in autism. The exposed animals spent less time interacting with unfamiliar peers and exhibited increased repetitive behaviors, such as excessive grooming. These effects could be mitigated by adding retinoic acid, confirming the link between the disruption of this pathway and the observed symptoms.

To understand the mechanisms at play, scientists studied human mini-brains grown in the laboratory from stem cells. These organoids, when exposed to montelukast, showed abnormalities in their development. Their size was reduced, and the expression of many genes related to retinoic acid signaling was altered. Additionally, the drug appears to promote the development of the brain’s ventral regions at the expense of the dorsal regions, thereby disrupting the balance between excitatory and inhibitory neurons. This imbalance is a feature often found in autism spectrum disorders.

Researchers also demonstrated that montelukast directly binds to retinoic acid receptors, preventing their normal function. By blocking these receptors, the drug disrupts the formation of protein complexes essential for gene expression regulation. This interaction explains why its use could have unexpected consequences on brain development.

A survey conducted among a large group of Chinese children also revealed that those who had taken montelukast before the age of three had an increased risk of developing an autism spectrum disorder. The data indicate a 37% increase in this risk compared to unexposed children. While this association alone does not prove causality, it strengthens the hypothesis that montelukast may contribute to the emergence of these disorders in some children.

These findings highlight the importance of reevaluating the safety of commonly prescribed medications, particularly in young children whose brains are still developing. They also remind us that the side effects of certain treatments can extend beyond their initial target and affect biological systems not directly related to their primary indication.

Bibliographie

Source de l’étude

DOI : https://doi.org/10.1038/s41392-026-02665-w

Titre : Anti-asthma drug montelukast induces autistic behaviors via disrupting neuronal retinoic acid signaling

Revue : Signal Transduction and Targeted Therapy

Éditeur : Springer Science and Business Media LLC

Auteurs : Zi-Jian Hao; Qiong-Hui Wu; Ya-Li Li; Zhen-Ming Guo; Zheng-Wei Li; Gui Wang; Meng Meng; Shi-Lin Yuan; Yilimire Wufuer; Meng-Huan Zhang; Jie Chen; Ting Yang; Meng-Xia Chen; Jiang Zhu; Wang Qi-Hang; Qiu Li; Shi-Hu Yu; Min Lu; Hai-Yi Xiong; Yu-Ru Feng; Meng-Qi Dong; Jun-Hao Xu; Jia-Lin Xu; Li Chen; Han-Ting Yang; Jing-Kun Miao; Hong Zhu; Bo Yang; Hui-Ying Zhao; Xiao-Ming Shi; Shan Bian; Ting-Yu Li; Rong-Gui Hu