One in three people will experience a seizure in their lifetime, and one in 26 will develop epilepsy. The cure can’t just be found in drugs, and Dr. Tara Klassen, an assistant professor in the UBC faculty of pharmaceutical science, is encouraging people to look deeper.
On October 27, the UFV biology department hosted a lecture on personalized medicine and molecular diagnostic risk prediction in epilepsy. Her research is primarily based on personalized medicine, since epilepsy is relatively common.
“[It’s about] the right drugs at the right time, in the right dose, for the right person,” she said.
Klassen defines epilepsy as “epilepsies” since it is not a single, unified disorder, but rather a phenotype. There are varying causes that contribute to this disorder, and the scope, range, and severity is different in everyone with epilepsy. That is why Klassen thinks researchers should be looking at individuals — right down to their genes — to help treat their particular condition.
“Treatment in epilepsy doesn’t prevent the development or prevention of the disease,” she said. “Currently, therapies are intervention-based.”
She said this is a major problem not only for doctors in providing the right type of personalized medicine for their patients, but also for families and patients who may be prescribed a one-size-fits-all diagnosis.
In her lecture, she touched on three distinct aspects of her research: the ion channel made up of protein molecules with disease genes, epilepsies that occur in pediatrics, and risk prediction. In the first half of her lecture, she introduced the structural functions of the ion channel. She states that it is the “single largest class of disease genes” that functions as both the primary cause for diseases and disease modifiers. A mutation in the voltage-gate of the calcium channel in particular can cause a range of disorders, such as neurological diseases, epilepsy, migraines, or development delays. This can vary depending on what part of the channels these mutations occur, and would be determined by the patient’s genes.
“There are 60 individual ion channel genes that are distinctly connected to 100 disease disorders,” Klassen said. “The problem is that they are both the cause of the disease, and yet the principal targets in drug therapies of diseases.”
For instance, the anti-epileptic drug (AED) acts like an ion channel that can either block or modify how the voltage-gate of the patient’s channel will act. The voltage-gate functions as a critical member of the molecule, as it opens and closes in response to the changes in the channel. However, this drug becomes problematic if the patient’s channel is already dysfunctional. Adding a drug like AED can backfire if the channel doesn’t accept it, as it creates a resistance to the drug itself.
Klassen said that in treatment there are many attempts to diminish the seizure frequencies, but they fail as they neglect to manage the other conditions that are caused by the same genes in the ion channels.
“The drugs are working only when the seizures are gone,” she said. “[However] we don’t try to actually stop any neurological delays.” For Klassen, this is where the role of genetic studies comes into play, as anticipating the cause of disease can be useful in preventative measures.
Predicting a patient’s risk for epilepsy is done through diagnostic testing where researchers can observe mutation patterns in an evolutionary context. Preventative risk assessments can also be done by creating an investigative data bank to catalogue all the diagnostic tests previously performed on patients. This includes literature about all documented gene mutations that can help determine the correlations between the mutations, the control population, or patients with extreme or rare conditions.
By using structural homology silicone models, Klassen’s team is able to run every mutation in the database and create genetic risk predictions for prospective parents. With these algorithm-based diagnostic tests, doctors can determine whether or not one or both of the parents have inherited a gene mutation. For example, if each of the parents is a “heterosite” — meaning that they individually have a single gene mutation copy — it may not be a major issue. However, the child may have a higher chance of inheriting both genes, potentially making them a “homosite,” and more susceptible to diseases such as epilepsy, diabetes, arrhythmia, cardiac diseases, and more.
Klassen strongly emphasized the critical need to continue observing gene mutations not only to reduce seizures and symptoms related to epilepsies, but also to personalize and predict specific gene mutations prior to birth.
Furthermore, she also explained that there is a need to understand epilepsies as being not only influenced by genetics, but also by environmental factors like other neurological and cardiac diseases. This is where the individual’s lifestyle plays a vital role in personalized medical treatments. With audio files from Kat Marusiak.