Indira David: new therapies for anxiety using psychopharmacology
Indira David has a PhD in neuropharmacology and is a engineer in the Moods team of the Centre for Research in Epidemiology and Population Health (CESP - Univ. Paris-Saclay, Inserm, UVSQ). She is passionate about psychopharmacology, and is working on developing new therapies to treat generalised anxiety.
Originally from Venezuela and of French-American nationality, Indira David was destined for an academic career at an early age. After completing a Master's in Science at John Jay College of Criminal Justice in New York, USA, in 1998 she was recruited as a technician at the Institute of Comparative Medicine at Columbia University, New York. This research unit looks at how axon guidance - a branch of neurodevelopment that studies how the part of the neuron conducting the electrical signal from the cell body to synaptic areas manages to find its target cells - develops in the visual pathways. In 1999, Indira David joined the Laboratory of Integrative Neuroscience at Columbia University, where she worked with Eric Kandel, winner of the Nobel Prize in Physiology or Medicine in 2000. She was promoted to research assistant in 2001. "It was during this period that my scientific adventure began and I developed a great interest in psychiatry." In 2005, she began a university education in neuroscience at the same university. She acquired extensive experience in behavioural studies and immunohistochemistry - a method of localising proteins in cells of a tissue section - and participated in numerous studies. One of these studies concerned the setting up of an animal model to better understand the neurobiological mechanisms at play during antidepressant treatment. The results of this work were published in the journal Neuron in 2009. "The article has been cited over 1,200 times to date," says Indira David.
A transatlantic career
After completing various scientific projects and successful collaborations with the Moods team at the CESP, Indira David specialised in neuropsychopharmacology. She crossed the Atlantic Ocean in 2010 to join the French team and complete a thesis in experimental and clinical pharmacology, in partnership with Columbia University. This thesis, which she defended in 2013, is entitled: Anxiolytic/antidepressant and neurogenic effects of 5-HT4 receptor ligands in mice: role of β-arrestin 1 protein. The aim was to identify the role of this serotonin receptor - i.e, a receptor in the nervous system activated by serotonin - in the management of anxiety and depressive disorder. In 2014, this work was rewarded the National Academy of Pharmacy thesis prize.
The limit of existing treatments
Indira David has been working in the field of psychiatry for more than 20 years, more specifically on the treatment of mood disorders, such as depression and anxiety disorders. Anxiety is one of the most common mental disorders in the French population, resulting in annual health expenditure of more than 40 billion euros. To treat it, clinical staff have in the past prescribed benzodiazepines. They now prefer to administer new molecules to patients to avoid the undesirable effects associated with physical and psychological dependence. These molecules are selective serotonin reuptake inhibitors (SSRIs) and other serotonergic agents with a role to play in anxiety. "But SSRIs have delayed therapeutic activity of several weeks, which can be a problem for many people. I have therefore focused my work on the development of new anxiolytics with rapid or even immediate action."
Activating the serotonin receptor 5-HT4R
Indira David demonstrated that by activating the serotonin type-4 receptor 5-HT4R, it is possible to develop a new strategy. Because rapid anxiolytic effects are induced by administering an agonist of this receptor - a molecule that interacts with the receptor and activates it.
Following these results, Indira David continued her work and was interested in the neurobiological mechanisms involved in rapid anxiolytic effects, whether following the activation of the 5-HT4R receptor or the administration of diazepam (a drug in the benzodiazepine family, such as Valium®, which has anxiolytic and sedative properties). The results highlighted the impact of the cortex-raphe brain circuit - involved in emotional processes - on rapid anxiolytic activity. This work was published in the prestigious journal Biological Psychiatry and the article was one of the most cited in the field of psychiatry in 2020.
Identifying new neural circuits
The engineer is also a multiple award winner. Notably in 2017 and more recently in 2022, when she received the National Alliance for Research on Schizophrenia and Depression Young Investigator Award by the Brain & Behavior Research Foundation. In 2018, she was awarded a research grant by the Deniker Foundation. "These awards mean that I can now go even further in my research, combining the pharmacological approach with optogenetics and fibre optic photometry, two new cutting-edge methods." Optogenetics is a technological revolution in the field of neuroscience. It involves genetically modifying neurons to make them sensitive to light, thanks to the expression of the opsin protein. Fibre optic photometry is a new calcium imaging technique which consists of visualising calcium in a cell or environment in order to study the activity of a given brain region. Using these methods, Indira David expects to identify the neural circuits and new 5-HT4R ligands involved in rapid anxiolytic response. For this work, she collaborates with the Division of Integrative Neuroscience of the Department of Psychiatry at Columbia University and the Biomolecules: Design, Isolation, Synthesis Laboratory (BioCis - Univ. Paris-Saclay, CNRS, CEA, Univ. Cergy-Pontoise).
Sharing a passion
Indira David is involved in various national and international master's programmes at Université Paris-Saclay. Her courses focus on drug and health product development, including animal models for psychopharmacology and optogenetics. "I particularly enjoy mentoring students, especially in the lab, to help them develop practical skills. I pass on my passion for scientific research. I think it helps to create new career interests."
Promoting women's access to research
In 2020 and 2021, Indira David was a recipient of the Travel Awards Program, awarded by the American College of Neuropsychopharmacology (ACNP), so she could present her research. She won the award in 2021 in the underrepresented minority category. Indira David is also actively involved in this area, as she supports access to research in neuropsychopharmacology for women from minority backgrounds, particularly those from Latin America. "They accounted for 7% in 1990 and 28% in 2019. I would like to see that percentage increase even faster in the next few years." To this end, she is also a member of the international organisation for women scientists, Graduate Women In Science. "These projects are important to me because my work teaches me that a project can only be successful if you work as a team. My motto is ‘Teamwork makes the dream work!’" concludes Indira David.
