A rare heart condition that kills young athletes has successfully been recreated in the laboratory by scientists uncovering its secrets.
The inherited disorder, called right ventricular dysplasia/cardiomyopathy (ARVD/C), can strike without warning leading to sudden death.
It accounts for up to 5% of fatal cardiac arrests in people under the age of 65, and is the leading cause of sudden death among young athletes.
ARVD/C usually presents no symptoms until the early 20s, making life difficult for scientists studying its development.
Now US researchers have managed to simulate the disorder by creating affected heart cells from patients’ skin.
The “disease-in-a-dish” reveals that the condition is linked to adult metabolism and abnormal activation of a protein called PPAR.
Scientists hope their model will help them develop new treatments.
The research involved taking ordinary skin cells from ARVD/C patients and reprogramming them.
Effectively, the cells’ developmental clock was turned back to an embryonic state. The modified cells, called induced pluripotent stem cells (iPSCs), had the ability to transform into any kind of tissue in the body.
The scientists coaxed them into becoming patient-specific heart muscle cells containing the faulty genes responsible for ARVD/C.
Further work showed how malfunctioning adult metabolism was at the core of the disease.
In the foetus, heart muscle cells get most of their energy from glucose. But after birth, they switch to using fat for energy production.
Only when the scientists triggered metabolic maturity in their model were they able to induce signs of the disease.
The research is published today in the latest online edition of the journal Nature.
Lead scientist Dr Huei-Sheng Vincent Chen, from Sanford-Burnham Medical Research Institute in La Jolla, California, said: “It’s tough to demonstrate that a disease-in-a-dish model is clinically relevant for an adult-onset disease. But we made a key finding here - we can recapitulate the defects in this disease only when we induce adult-like metabolism.
“This is an important breakthrough considering that ARVD/C symptoms usually don’t arise until young adulthood.”
Colleague Dr Daniel Judge, from Johns Hopkins University, said: “With this new model, we hope we are now on a path to develop better therapies for this life-threatening disease.”