Eine neue intranasale RNA-Therapie verspricht, das Gedächtnis zu stärken und Angstzustände zu reduzieren, indem sie die Aktivität eines bestimmten Serotoninrezeptors im Gehirn verringert, was zu erheblichen Verbesserungen des Gedächtnisses und einer Verringerung angstähnlicher Verhaltensweisen in Nagetiermodellen führt.

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.