Tuesday , January 31 2023

Deciphering Candidates for treating irregular heartitis


In 2015, then President Barack Obama launched an initiative for precision medicine, saying his promise was "to provide the right treatment, at the right time, every time to the right person." Biomedical Engineer at Washington University in St. Louis responded by calling to make a significant step towards the precise treatment of patients with a dangerous form of irregular heartbeat by determining in which patients will most often use the treatment of drugs.

Jonathan Silva, associate professor of biomedical engineering at the School of Engineering and Applied Sciences, was part of an international team to determine which patients will most benefit from the most commonly used treatment.

The results of the research are published online Circulation research December 18th.

Silva has teamed up with leading authors Vandi Zhu, a doctoral candidate in his lab and associates from the University of Pavia in Italy. Together they examined the efficacy of medicinal mexiletin in patients with genetic mutation that causes Long KT type 3 syndrome, a disorder that results from heart failure to properly repolarize, leading to irregular heartbeat – or arrhythmia. Lek was given to patients with long KT syndrome in the decade, but was ineffective, sometimes even harmful, to the majority. Silva's team wanted to find out why.

Traditionally, researchers could only look at certain variables in the heart. Silva's approach was to create a statistical model that links the variables of a patient's phenotype or physical expressions of genetic traits. Using fluorometry, a technique that alters changes in the environment of a fluorescence molecule, understood the interaction of nanometric mexiletin in the sodium channel of the heart.

"What we were told was that there was a special role in the domain of the voltage sensor in the domain, which was essentially in correlation with the effect of the drug," Silva said. "While the theories we have linked to the regulation of drug blocks with a certain conductive channel status, we have linked it to a certain part of the channel. This improved understanding of how the channel operates and how this part affects the block of blocks has enabled us to determine this prognosis that will patients react? "

To test his theory, Silva and his team examined 15 different mutations from patients diagnosed with Long KT 3 syndrome and found a very strong correlation with one of the electrical gateways of the sodium channel known as Domain III sensing domains, but not from the traditional variables are used.

"It gave us a lot of confidence that the domain of the three sensor voltage sensors controls the patient's response to the drug," he said.

The team then applied their theory to blinded data from eight Priori patients in Italy. When Silva team members forwarded their prediction to the researchers, they found that they had correctly predicted for seven out of eight patients.

Then, the team plans to conduct a larger clinical trial of its method.

"Now that we have strong evidence that this part of the canal regulates a drug block, we want to use a similar approach to a much larger set of patients," he said. "We want to see if we can apply these methods that apply to the disease line and use a similar approach to understand how usually prescribed drugs affect the usual arrhythmias."

This article was published on the materials provided by the Washington University of St. Louis. Note: The material may have been edited for length and content. For further information, please contact the quoted source.


Zhu, V., Mazzanti, A., Voelker, T., Hou, P., Moreno, J. D., Angsutararuk, P.,. . . Silva, J. R. (2018). Prediction of the patient's response to anti-arrhythmic mexiletin based on genetic variation: personalized medicine for long KT syndrome. Circulation research. doi: 10.1161 / circresaha.118.314050

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