Safety assessments are a critical component of taking a potential pharmaceutical compound down the path from discovery to prescription drug. However, it is often difficult to assess whether a drug will affect everyone the same. Over the past few decades, doctors and researchers have gained awareness of how a person’s genetics, co-occurring chronic conditions or diseases, and other medications they are taking can interact with a drug, dramatically altering how their body responds to it. These interactions can be difficult to predict in standard safety trials using animals or healthy volunteers and are often not discovered until a medication goes to market. Concern over this possibility has led to the rise of personalized medicine – medications and treatment plans tailored to the needs of individual patients. However, developing interventions for rare diseases or uncommon situations is often easier said than done with standard testing methodologies due to the difficulty or replicating some conditions in animals or the small number of human volunteers for clinical trials. Fortunately, stem cell technology is providing options for researchers to create novel models of cellular behavior that can quickly predict risks of a medication for a particular patient.
Irregular heartbeat, or heart arrhythmia, is a potentially dangerous side effect of many medications and is a key metric when testing the safety of a new drug. Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) are heart muscle cells that have been taken from the hearts of healthy volunteers and grown in the lab. Their unique stem cell properties allow them to be influenced to mature into different types of cardiac cells. hiPSC-CM can be used to demonstrate how different conditions, like sodium levels or the presence of a drug compound, impact the heartbeat. They allow researchers to predict what would happen if a person’s heart was exposed to the same conditions and can help rule out potentially dangerous drugs well before animal trials and human clinical studies.
The use of hiPSC-CM is not limited to modeling healthy cardiac cells. Thanks to their powerful stem cell properties, hiPSC-CM can be manipulated to replicate common heart conditions or genetic disorders. This makes them a potentially powerful tool in developing personalized medicine. While traditional drug assessment requires extensive animal studies and human trials to figure out the potential impact of a new compound, multiple hiPSC-CM cultures can easily be generated in the lab and subjected to a wide range of tests. While they cannot fully replace animal and clinical trials for evaluating medications, they provide researchers with the ability to understand the mechanics of how a drug interacts with cells and rule out compounds that are dangerous early on.
The ability of hiPSC-CM to replicate a wide range of health conditions offers a potential solution for developing complex personalized medicine interventions. These cells allow researchers to quickly assess numerous factors, such as how a new drug might interact with a patient’s current medications or their unique genetic profile to cause arrhythmia. For example, some people carry a rare mutation of a gene that impacts how long cardiac cells need to rest between contractions – i.e. how fast they are capable of beating. A person carrying this mutation would be at higher risk for developing an arrhythmia using medications that would be safe for most other people. hiPSC-CM can be easily manipulated to express the mutation of concern and evaluate if a drug is likely to cause problems for a patient with that genetic profile. Further, work in cellular models allows researchers to observe and understand how drug compounds interact with cells at the molecular level, increasing their ability to predict how drugs with similar mechanisms with impact different demographics of patients.
As doctors are increasingly seeking ways to tailor medical interventions to the specific needs of an individual patient, tools for assessing personalized medicine strategies are critical. hiPSC-CM cell lines allow researchers to replicate the behavior a patient’s cardiac cells quickly and effectively, without additional stress or risk to the patient. hiPSC-CM can help prevent drug-induced arrhythmia in patients with high-risk complications, decreasing drug liability and increasing successful clinical outcomes.