Targeting the RHOA pathway improves learning and memory in adult Kctd13 and 16p11.2 deletion mouse models.
Sandra Martin Lorenzo, Valérie Nalesso, Claire Chevalier and 2 others
PMID 33436060WHAT IT FOUND
In mice with genetic deletions linked to autism and intellectual disability, the drug fasudil improved object recognition memory but did not fix object location memory or hyperactivity.
These findings are preclinical and do not yet offer a treatment for human patients.
Key findings
01Chronic treatment with fasudil significantly improved the deficit in novel object recognition memory in both Kctd13 heterozygous and 16p11.2 deletion mouse models.
02Fasudil treatment failed to restore novel object location memory in the 16p11.2 deletion model and did not reduce the hyperactivity seen in these mice.
03The drug normalized the over-activation of the RHOA/ROCK signaling pathway, evidenced by reduced phosphorylation of the Myosin Light Chain in the hippocampus.
STILL TO COME
How it was doneWhat they found
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What it does not show
The study was conducted entirely in animal models, not humans. The mouse models replicate only a partial set of features found in humans with 16p11.2 deletion syndrome. The study was limited to viable mutant animals on a pure genetic background, which may not reflect the full range of the condition. The drug did not address all cognitive deficits (object location) or behavioral symptoms (hyperactivity) present in the models.
Declared interests
The study was funded by the Agence Nationale de la Recherche and the Fondation pour la Recherche Médicale in France. No commercial conflicts of interest were declared.
The easy way to misread this
Do not interpret the improvement in mouse object recognition memory as evidence that fasudil will improve human learning or communication. The drug failed to correct other key deficits like object location memory and hyperactivity in the same animals, and the models do not fully replicate human symptoms.