Multiple Models for Researching the Complexities of PAH
To state it simply, pulmonary arterial hypertension is a complex disease.
Our labs have generated substantive data, and after numerous conversations with colleagues, it is clear that researching this disease from multiple aspects is likely the most efficient way to help find new treatments.
We recently presented a comprehensive overview of our PAH findings at a Lunch and Learn at the 2014 Safety Pharmacology Society Annual meeting and again for a client project team.
Over the past several years, companies were focused on providing benefit to PAH patients primarily through a hemodynamic mechanism such as selective pulmonary arterial vasodilation. Recently, the paradigm has shifted to focus more on the remodeling and inflammatory processes associated with the development of PAH.
Although the hypoxia / VEGF antagonist treated rat continues to be the gold standard animal model of this disease, increasingly we have been conducting experiments using a T-cell deficient rat co-treated with VEGF antagonist. This model is dependent on dysregulated immunity contributing to increased inflammation that exacerbates PAH.
Our results showing a protective effect with the LTA4 hydrolase inhibitor bestatin are consistent with the literature. In addition, we now have data demonstrating that sildenafil (PDE5 inhibitor – hemodynamic effect) shows efficacy in this ‘inflammatory’ model as well. A recent article has also shown that sildenafil has an anti-inflammatory effect in monocrotaline treated rats.
Research into developing additional and better treatments for PAH continues at a rapid and growing rate. We are also discovering new mechanisms by which current options exert efficacy. By continuing to refine the animal models of this disease, we stack the odds of success in our favor.
Related Posts via Categories
- Pulmonary Arterial Hypertension,
- Pulmonary Arterial Hypertension Drug Discovery,
- Safety Pharmacology Society