Background
Central Nervous System (CNS) Disorders include neurological, neurodegenerative and neuropsychiatric disorders and have a huge impact on the individual but also contribute to a substantial healthcare, societal and economic burden. Neuropsychiatric conditions include mental health disorders such as anxiety, depression, post-traumatic stress disorder (PTSD). The incidence and impact of mental health conditions is rising however the development of new therapies is lagging behind. There are limited therapeutic options for many of these conditions and the 3 main categories of drugs used are anxiolytics, anti-depressants and anti-psychotics. All of which have significant drawbacks; limited efficacy, delayed action, side effects, impact on other medications, impacts for women of childbearing age, breastfeeding etc. Many of these negatives are due to the fact that the pharmacology of the drug is not specifically targeting the disease pathophysiology.
Aims
To identify new drug targets we must first look at the disease pathophysiology to identify the dysregulated molecular mechanism. This requires access to tissue samples from patients which in CNS conditions is incredibly challenging as the brain is the organ of interest. Translationally relevant animal models which recapitulate aspects of the clinical disease are the appropriate option in this regard. In my project, I will screen changes in stress-related gene expression in brain tissue collected from an animal model of PTSD. Drugs treating CNS conditions are notably difficult to design, develop and test due to the major hurdle in this field which is crossing the blood brain barrier. The second aim of my project is to assess different formulation strategies to optimise brain delivery of novel compounds.
Outcome
Overall my project will assess which specific neuronal pathways are dysregulated in PTSD and begin to formulate novel compounds which are designed to have enhanced blood brain barrier permeability.