Hypertrophic cardiomyopathy (HCM),a severe and life limiting disease is the most common feline heart condition. In humans, HCM is associated with mutations affecting contractile proteins in the heart. Similar mutationsaresuspected to cause HCM in cats and specific mutations have been identified in two breeds(Ragdoll and Maine Coon).These mutations cause the heart muscle cells tobecomeenlarged leading to thickening and scarring of the heart wall which affectsthe hearts ability to pumpefficiently. These processes lead to heart failureand breathlessness, or paralysisdue to blood clots and even sudden death. No therapy currently can halt the progression of this severe disease.
To date, only limited treatment options are available because the process by whichthese mutations lead toa thickened and scarred heart muscle arepoorly understood. The lack of suitable cellular disease modelsmeans that progress identifying these pathological processes has been painfully slow.Using newer genetic engineering techniques,we have recentlybeen able to introduce the Ragdoll HCM-causing mutation into human pluripotent stem cells (iPSCs). These iPSCs can be turned into heart muscle cells, providing an unlimited supply of diseased cells to study these pathological pathways. We next want to use a technology known as RNA-sequencing to identify these pathways and determine whether they are leading to the excessive enlargement of the muscle cells. If they are, this will enable us to develop newdrugtreatments for HCM applicable toall catsby identifying ways of closing down these pathways.