Sunday , November 29 2020

Decryption of irregular heartbeat candidates

By 2015, President Barack Obama launched a Precision Medicine Initiative, saying that its promise was to "deliver the right treatments at the right time every time to the right person." A biomedical engineer at Washington University in St. Petersburg. Louis has responded to the call by making an important step towards precision medicine for patients with a life-threatening form of irregular heartbeat by determining which patients would be most beneficial in the treatment of drug treatment.

Jonathan Silva, associate professor of biomedical engineering at the School of Engineering & Applied Science, was part of an international team who identified which patients benefited most from a commonly used treatment.

The results of the research are published online in circulation Research December 18th.

Silva was with Wandi Zhu, a PhD student in her laboratory and collaborators from Pavia University in Italy. Together, they investigated the effect of the drug mexiletin on patients with a genetic mutation that causes Long QT Syndrome Type 3, a disorder caused by the inability of the heart to correct repolarization, leading to irregular heartbeat or arrhythmias. The drug has been given to Long QT Syndrome patients for ten years, but was ineffective, sometimes even harmful to a majority. Silva's team wanted to learn why.

Traditionally, researchers have only been able to look at certain variables in the heart. Silva's laboratory approach was to create a statistical model that connects the variable characteristics of a patient's phenotype or the physical expressions of a genetic trait. Using fluorometry, a technique that measures changes in the environment of a fluorescent molecule, they understood the nanoskaline reaction of mexiletin in the heart's sodium channel.

"What told us was that there was a lot, especially in Domain III-sensitive domain that was really correlated with the drug effect," Silva said. "While theories before us had linked the regulation of the drug block to a particular conductive state of the channel, we bound it to a particular part of the channel. This improved understanding of how the channel works and how this part affects the drug block allowed us to do This prediction as to whether the patients will respond or not. "

To test their theory, Silva and his team found 15 different mutations from patients diagnosed with Long QT 3 syndrome and found a very strong association with one of the sodium channel's electrical ports called Domain III Sensitivity, but not with The traditional variables used.

"It gave us great confidence that the domain's three sensitive domains control the patient's response to the drug," he said.

The team then used its theory of blind data from eight patients from the Priori group in Italy. When Silva team members returned their predictions to the researchers, they discovered that they had predicted correctly for seven of the eight patients.

Next, the team plans to conduct a major clinical trial with its method.

"Now that we have strong evidence that this part of the channel regulates the drug block, we will use a similar approach to a much larger number of patients," he said. "We want to see if we can take these methods that apply to a rare disease and use a similar approach to understanding how commonly prescribed drugs affect more common arrhythmias."

This article has been reissued from materials provided by Washington University in St. Petersburg. Louis. Note: The material may have been edited for length and content. For more information, please contact the specified source.


Zhu, W., Mazzanti, A., Voelker, T., Hou, P., Moreno, J. D., Angsutararux, P.,. . . Silva, J.R. (2018). Predicting Patient Response to Antiarrhythmic Mexiletin Based on Genetic Variation: Personal Medicine for Long QT Syndrome. circulation Research. doi: 10,1161 / circresaha.118.314050

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