Scientists from Columbia University Medical Center in the laboratory of Robert Kass have used a heart patient’s cells to make induced pluripotent stem cells (iPSCs) that were then differentiated into heart muscle cells. These heart muscle cells were used to test drug strategies to keep the patient’s heart going.
This patient, you see, suffers from Long QT syndrome (LQTS), which is caused by an abnormal ion channel in the heart. LQTS affects the patient’s heart rhythm, which result in fast, chaotic heartbeats. These rapid heartbeats may trigger sudden fainting or a seizure. In some cases, the heart may beat erratically for so long that it can cause sudden death.
Long QT syndrome is treatable by means of decreased physical activity, and certain medicines. Other patents will need surgery or an implantable device.
In this case, the four-year-old patient responded poorly to medicines. Therefore, to find the right combination of drugs, The child had a mutation in the SCN5A gene, which encodes the alpha subunit of the voltage-gated sodium channel. However, this child also had a mutation in the KCNH2 gene, which encodes a potassium channel. This child’s LQTS, therefore, was particularly severe and did not respond to the usual drug regimens.
By using an electrophysiological test called “voltage clamping” on the heart muscle cells made from the patient-specific iPSCs, heart doctors were able to find a drug treatment strategy that eventually stabilized the patient’s heart and saved his small life.
Voltage clamping is a technique used to control the voltage across the membrane of a small or area of a nerve or heart muscle cell by means of an electronic feedback circuit. By sucking a small part of the cell membrane into a micropipette that has a tiny wire in it (yes it sounds hard and yes it is hard), the voltage is increased gradually and the circuit required to hold the voltage at each level is measured. This current is the same as the ionic current that flows across the membrane in response to the applied voltage. This ionic current tells the heart specialist all about what ion channels are present and how well they work in the presence or absence of particular drugs.
These results demonstrate the power of iPSCs in culture as a model system to determine patient-specific therapies.