Scientists from Cognigenics have made significant progress in developing precision-based therapeutics for neurological disorders. In a groundbreaking study, they successfully used a non-invasive intranasal delivery platform to administer short-hairpin RNA (shRNA) that targets the 5-HT2A receptor resulting in long-lasting improvements in memory and reduced anxiety in animal models.

Neurological disorders such as Mild Cognitive Impairment (MCI), depression, and anxiety disorders pose significant challenges to public health worldwide. Despite extensive research efforts, effective treatments for these conditions have been limited. However, the emergence of precision-based therapeutics, including shRNA and CRISPR/Cas9, offers new hope for tackling these debilitating disorders.

In this study, the researchers designed shRNA sequences to specifically target and silence the human HTR2A gene, which is associated with anxiety and memory. To navigate the obstacle of the blood-brain barrier (BBB), a significant hurdle in delivering gene therapies to the brain, the researchers utilized adeno-associated viral (AAV9) vectors via intranasal delivery, efficiently bypassing the BBB and effectively targeting the central nervous system. AAV9 vectors containing Cognigenics’ novel shRNA sequences were administered in both mice and rats, resulting in a 92% improvement in memory in rats, a 104% improvement in memory in mice, and a significant decrease in anxiety behavior in mice as compared to control animals.

The successful demonstration of this non-invasive shRNA delivery platform holds tremendous potential for a wide range of neurological disorders. By specifically targeting the HTR2A gene, the researchers have identified a novel therapeutic approach for treating anxiety and cognitive decline.

Prof. Troy T. Rohn, the lead researcher, expressed his optimism about these findings, stating: "Our study showcases the power of shRNA in modifying neuronal circuits underlying behavioral traits. The ability to bypass the blood-brain barrier using intranasal delivery opens up new avenues for precision-based therapeutics in neurological disorders."

The research team believes that developing shRNA-based therapies could revolutionize the treatment landscape for neurodegenerative and neuropsychiatric disorders. Unlike CRISPR/Cas9, shRNA induces temporary gene silencing, making it a promising tool for targeted and reversible interventions.

David Pyrce, CEO of Cognigenics added, “This study established a significant step forward in highlighting the breakthrough potential of using intranasal delivery of shRNA to precisely target the 5-HT2A receptor in neurological disorders, representing a promising new therapeutic option to improve memory and alleviate anxiety. We are now focused on fast-tracking development to bring this novel therapeutic approach to clinical care as rapidly as possible.”

Detailed findings of this study were published in the March 20, 2024 issue of Translational Psychiatry in an article entitled "Intranasal Delivery of shRNA to Knockdown The 5-HT2A Receptor Enhances Memory and Alleviates Anxiety" authored by Troy T. Rohn, Dean Radin, Tracy Brandmeyer, Peter G. Seidler, Barry J. Linder, Tom Lytle, John L. Mee & Fabio Macciardi. The open access article is available here: https://link.springer.com/article/10.1038/s41398-024-02879-y

About COG-201:

COG-201 is an intranasally-delivered therapy deploying the tools of precision medicine using short-hairpin RNAs (shRNA) to target and selectively knockdown 5-HT2A serotonin receptor mRNA and protein. In in vivo studies, COG-201 has demonstrated a significant improvement in memory (92%), while also decreasing anxiety-like behavior in mice as compared to vehicle-treated animals. COG-201 is currently transitioning to IND-enabling studies with human clinical trials planned for 2025.

About Cognigenics:

Cognigenics is a pioneering biotechnology company specializing in precision-based neurogenetic therapeutics for neurological disorders. With its innovative intranasal delivery platform, Cognigenics aims to revolutionize the treatment landscape for debilitating neurological conditions.

More information about Cognigenics:

Website: https://www.cognigenics.io/

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