Life Sciences & Biotechnology
Title : | Characterising a novel potential antidepressant drug that activates the RXFP3 receptor. |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Somasish Ghosh Dastidar, Manipal Academy Of Higher Education, Karnataka |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | somasish.gd@manipal.edu |
Equipments : | Mechanical pipettes
Mechanical pipette
Mechanical Pipette |
Details
Executive Summary : | RXFP3 (Relaxin Family Peptide 3 Receptor) is a neurotransmitter receptor expressed within the brain, and is an exciting target for the development of novel antidepressant drugs. For example, rodent studies have shown that drugs which active RXFP3 (agonists) reduce anxiety and display other antidepressant-like actions. However, these early versions of RXFP3 agonists have required direct brain injection, as they do not cross the blood brain barrier (BBB). This approach is associated with a range of problems, such as the need for surgical implantation of a guide cannula, and uneven drug distribution within the brain. Therefore, the crucial next step is to develop and characterize an RXFP3 agonist that crosses the BBB, and demonstrate its antidepressant actions following peripheral injection. To achieve this goal, this project will collaborate with world leaders in the RXFP3 field, allowing access to recently developed BBB-penetrating RXFP3 agonists that display exciting in vitro pharmacological properties. This project will screen four RXFP3 agonists, and determine which elicits the most promising acute changes in depression-relevant behaviors in mice and rats. The pharmacological specificity of this best performing RXFP3 agonist will be confirmed using RXFP3 knock-out mice, as on-target RXFP3 drug effects will not be present within this strain of mouse. Importantly, we will also determine the therapeutic potential of chronic RXFP3 agonist treatment in a mouse model of depression, and the acute and chronic mechanisms of action will be characterized via whole transcriptome sequencing of key brain regions post treatment. Taken together, this project will help validate the therapeutic potential of RXFP3, and will help fast-track the development of an RXFP3 agonist for the treatment of depression by laying the foundation for future clinical trials. |
Total Budget (INR): | 30,33,288 |
Organizations involved