New intranasal RNA therapy shows promise in boosting memory and reducing anxiety, by decreasing the activity of a specific serotonin receptor in the brain, leading to significant improvements in memory and reductions in anxiety-like behaviors in rodent models.

I’ve linked to the news release in the post above. In this comment, for those interested, here’s the link to the peer reviewed journal article:

https://gp.genomicpress.com/wp-content/uploads/2024/08/GP0043-Rohn-2024.pdf

From the linked article:

A recent study published in Genomic Psychiatry has unveiled a promising new therapy that may help improve memory and reduce anxiety. The study, conducted by scientists at Cognigenics, explores the potential of an innovative intranasal treatment known as COG-201. This therapy uses RNA-based technology to decrease the activity of a specific serotonin receptor in the brain, leading to significant improvements in memory and reductions in anxiety-like behaviors in rodent models.

The study used COG-201, an intranasal therapy based on short hairpin RNA (shRNA). This RNA molecule is designed to interfere with the expression of the serotonin 5-HT2A receptor gene, reducing its activity in the brain. The therapy was administered through a nasal spray, making it non-invasive and potentially easy to use in future clinical settings.

To evaluate the therapy’s effects, the researchers conducted experiments on animal models, specifically mice and rats. They first developed a shRNA designed to reduce the production of the serotonin 5-HT2A receptor by targeting its gene, HTR2A. The treatment was delivered using an adeno-associated virus (AAV9) vector, which served as a carrier to transport the shRNA into the neurons.

The results of the study were promising. Animals treated with COG-201 displayed significant improvements in memory and reductions in anxiety-like behaviors. In the novel object recognition test, treated rats spent considerably more time exploring new objects compared to untreated animals, indicating better memory retention. The researchers calculated a discrimination index, a measure of memory performance, and found that the treated group scored 22.5% higher than the control group, which exhibited a negative score.

On the anxiety front, the treated animals showed reduced anxiety-like behaviors in anxiety-inducing environments. This suggested that COG-201 may have a dual benefit: improving memory while also alleviating anxiety.

The molecular data supported these behavioral findings. The researchers confirmed that the intranasal delivery of COG-201 effectively reduced the expression of the serotonin 5-HT2A receptor in the brains of both mice and rats. There was a 38% reduction in receptor mRNA levels and a corresponding 34% decrease in receptor protein levels in treated neurons. This knockdown of receptor expression was directly linked to changes in neuronal activity. Neurons in treated animals showed a decrease in electrical activity, which aligns with the theory that reducing serotonin 5-HT2A receptor activity could dampen the excitatory signals that contribute to anxiety and memory deficits.