Project B19
Development and pharmacological characterisation of a pig model for primary aldosteronism
Project B19 addresses a novel approach to understanding and treating primary aldosteronism, a common form of high blood pressure caused by the overproduction of the hormone aldosterone from the adrenal gland/s. In many patients, this condition is driven by specific mutations in the KCNJ5 gene. Existing treatments can have significant side effects, creating a critical need for better research models and new therapeutic options. To address this, we have developed a novel genetically engineered pig model that carries a key human disease-causing mutation (KCNJ5-T158A). Pigs were chosen because their adrenal biology is similar to humans, making them a more relevant model than rodents for this research. We have successfully established a breeding colony of these mutant pigs. Initial studies confirm early signs of disease, including changes in adrenal tissue structure and hormone levels. We are now actively investigating how factors like diet can influence the progression to full-blown disease. In parallel, we are using advanced computational methods to discover new drugs that can specifically target the dysfunctional KCNJ5 channel. Promising candidate molecules have been identified and are currently being validated in laboratory assays. This powerful combination of a human-relevant animal model and targeted drug discovery will accelerate our understanding of primary aldosteronism and pave the way for more effective, personalised treatments for this widespread form of hypertension.
Aims
(I) To investigate and extend the knowledge of constitutive aldosterone production and adrenal pathology resulting from a hereditary pathogenic KCNJ5 variant in a porcine model to better understand the underlying mechanisms of hyperaldosteronism.
(II) Determine the spectrum of clinical and functional alterations beyond adrenal pathology caused by pathogenic KCNJ5 variants to gain insight into the systemic effects of these variants.
(III) Identify novel small molecule compounds that specifically modulate the function of pathogenic variants of the KCNJ5 potassium channel.
| Principal Investigators | Institution |
| Prof. Dr. med. vet. Eckhard Wolf | LMU |
| PD Dr. med. vet. Elisabeth Kemter | LMU |
| Tracy Ann Williams, PhD | LMU |
