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W17-008: Growing heart muscle cells in a dish in the lab to test HCM treatments

Hypertrophic cardiomyopathy (HCM) is a common and severe feline disease. It is caused by mutations (genetic alterations) affecting the contractile proteins of the heart muscle cells (cardiomyocytes) which alters their internal functioning causing them to contract too vigorously and become enlarged. Over time this causes the walls of the heart to become thickened and stiff which reduces its ability to pump blood efficiently. Eventually this leads to the distressing clinical signs associated with HCM including severe breathlessness, paralysis due to blood clots, or sudden death. There is no therapy at present that can prevent disease progression.

The primary investigators have recently identified a family of molecules which rectify the abnormal functioning of the mutant heart proteins in cats with HCM by reducing their force of contraction. In time, they hope these molecules will also be effective in preventing HCM in live cats. However, they must first show that these molecules work and are safe in living cardiomyocytes. Unfortunately, it is not possible to grow cardiomyocytes in the laboratory and this is a major obstacle to progressing their work. However, using recent technology the investigators can convert skin cells from cats with HCM into heart muscle cells. Cardiomyocytes made in this way can be grown for long periods in the laboratory and importantly display all the disease characteristics of cardiomyocytes from cats with HCM, allowing researchers to test the safety and ability of these and other novel molecules to alter disease progression at the cellular level before using them to treat affected cats.

Ricky Fund Study (Sponsored by Holly Aglialoro in memory of Augustus)

Grant ID: W17-008

Status: Active

Year Funded: 2017

Amount awarded: $17,158

Investigator: David Connolly; The Royal Veterinary College; Debbie Guest; The Animal Health Trust; Cesare Terracciano, Imperial College London