Cardiac (heart) arrhythmias occur when electrical impulses that coordinate your heartbeats don’t work properly, causing your heart to beat too fast, too slow, or in an irregular manner. In the U.S. alone, almost one million individuals are hospitalized every year for heart arrhythmias. Close to 300,000 individuals die of sudden arrhythmic death syndrome every year, which occurs when there is a sudden loss of blood flow resulting from the failure of the heart to pump effectively. Unfortunately, drugs to treat arrhythmias have liabilities and several drugs have been pulled from the market due to serious side effects. Mexiletine is one potential drug for heart arrhythmias that has liabilities and potential side effects.
That is why a CIRM funded study ($6.3 million) conducted by John Cashman, Ph.D. at the Human BioMolecular Research Institute in San Diego looked at re-engineering mexiletine in a way that the drug could still produce a desired result and not be as toxic.
The study used induced pluripotent stem cells (iPSCs), a type of stem cell “reprogrammed” from the skin or blood of patients that can be used to make virtually any kind of cell. iPSCs obtained for the study were from a healthy patient and from one with a type of heart arrhythmia. The healthy and arrhythmia iPSCs were then converted into cardiomyocytes, a type of cell that makes up the heart muscle.
By using their newly created healthy cardiomyocytes and those with the arrhythmia defect, Cashman and his team were able to carry out drug development in a dish. This enabled them to attempt to lessen drug toxicity while still potentially treating heart arrhythmias. The team was able to modify mexiletine such that is was less toxic and found that it could potentially decrease a patient’s risk of developing ventricular tachycardia (a fast, abnormal heart rate) and ventricular fibrillation (an abnormal heart rhythm), both of which are types of heart arrhythmias.
“The new compounds may lead to treatment applications in a whole host of cardiovascular conditions that may prove efficacious in clinical trials,” said Cashman in a press release. “As antiarrhythmic drug candidate drug development progresses, we expect the new analogs to be less toxic than current therapeutics for arrhythmia in congenital heart disease, and patients will benefit from improved safety, less side effects and possibly with significant cost-savings.”
The team hopes that their study can pave the way for future research in which cells in a dish can be used to lessen the toxicity of a potential drug candidate while still producing a desired result for different diseases and conditions.
The full study was published in ACS Publications.
One thought on “CIRM funded study uses drug development in a dish for treatment of heart arrhythmias”
In the early of cell development, stem cells are mobile, they move from one to the other location and search for growth factor which is essential for growth and differentiation. The progenitor cells require various stages of maturation before attaining the late stage of differentiated cells. The mature cells are active, functional and adherence. The adherence of mature cells are depended on cell-surface interaction both with molecules on the surface of the other cells and the extracellular matrix.
The technology of iPSCs derived cardiomacyocytes are considered early stage of stem cells. They are moveable and lack of nerve cells and blood circulation to support their growth and functional. Experimental study to investigate the safety and efficacy of medicine on patients iPSCs organoids may not always translate effective clinical outcome. The early stage of cells are not always have similar cellular structure and molecules to mature cells . Both stages of cells may produce diverse phamacokinetic action against similar drugs. Therefore, the results of experimental study on patients iPSCs organoids with drugs provide very little clinical information to support safety and efficacy of drugs on patients .