- A cardiac arrhythmia occurs when the heart beats irregularly.
- The most common type of cardiac arrhythmia is atrial fibrillation, which can lead to stroke or heart failure.
- Researchers from the University of Chicago have found a drug used to treat certain cancers and skin conditions can be repurposed to help treat cardiac arrhythmias.
A person experiences a cardiac arrhythmia when their heart beats too quickly, too slowly, or irregularly.
The most common type of cardiac arrhythmia is called atrial fibrillation. This occurs when the upper and lower chambers of the heart become uncoordinated, affecting blood flow.
Sometimes atrial fibrillation can lead to severe complications, such as stroke and heart failure.
Previous research shows about one in five people with atrial fibrillation die during the first year after diagnosis.
Now, researchers from the University of Chicago have found a drug used to treat certain cancers and skin conditions called ruxolitinib can be repurposed to help treat cardiac arrhythmias.
This study was recently published in the journal Science Translational Medicine.
CaMKII inhibitors and cardiac arrhythmia
For this study, researchers began by looking for potential CaMKII inhibitors.
“CaMKII is abundant in heart muscle cells where under physiological circumstances it promotes performance,” Dr. Mark Anderson, Executive Vice President for Medical Affairs, Dean of the Division of the Biological Sciences (BSD) and Dean of the Pritzker School of Medicine at the University of Chicago, IL, and senior author of this study explained to Medical News Today.
“For example, CaMKII contributes to heart rate increases and improved muscle performance, as part of a ‘fight or flight’ stress response,” he said.
“However, excessive CaMKII activity causes electrical instability of the heart muscle cell membranes — mostly by activating electrical proteins called ion channels. Inhibiting CaMKII stabilizes the cell membrane currents, thereby preventing or stopping arrhythmias,” he explained.
What is ruxolitinib?
Ruxolitinib is in the class of medications known as Janus kinase inhibitors.
Janus Kinases are a family of non-receptor tyrosine kinases — an enzyme important in many cell functions, including cell growth and signaling.
In 2011, ruxolitinib received approval from the U.S. Food & Drug Administration (FDA) for treating myelofibrosis. Myelofibrosis is a rare blood cancer occurring in the bone marrow, making it hard for blood cells to be made.
And in 2015, the drug became the first U.S. FDA-approved medication for polycythemia vera — a blood disorder that is also considered a type of blood cancer.
In September 2021, the U.S. FDA approved ruxolitinib for topical cream treatment for the skin condition atopic dermatitis, also known as eczema.
And in September 2022, ruxolitinib was also approved for use in treating vitiligo — a skin condition where the cells that make melanin die off, causing patches of skin to lose their color.
A surprising discovery
During their research, Dr. Anderson and his team identified five previously unknown CaMKII inhibitors out of 4,475 potential medications.
Of those five, ruxolitinib was reportedly the most effective, which, Dr. Anderson said, was surprising to them.
“First, we did not have a clear expectation that any of the screened drugs would have potently inhibited CaMKII,” he said.
“That said, we were not surprised that a kinase inhibitor drug could ‘cross over’ to inhibit CaMKII. However, ruxolitinib is a JAK1/2 inhibitor and these kinases are not closely related to CaMKII. Thus, we would have anticipated that an inhibitor targeting a more closely related kinase would have been identified,” he continued.
Using both cell and mouse models, scientists found just a 10-minute application of ruxolitinib was enough to prevent catecholaminergic polymorphic ventricular tachycardia (CPVT) — a condition that causes cardiac arrhythmia in children — and rescue atrial fibrillation.
Researchers stated they believe new drugs based on their findings could be used in a variety of ways, including when atrial fibrillation symptoms first start to treating children with catecholaminergic polymorphic ventricular tachycardia, who are many times resistant to standard treatments.
No adverse cognitive effects
The researchers also mentioned there has been some apprehension in developing therapies targeting CaMKII inhibition as CaMKII plays a vital role in brain function, including learning and memory.
However, Dr. Anderson and his team reported the mice treated with ruxolitinib did not show any adverse cognitive effects when tested with memory and learning tasks.
“We think this finding may reduce concerns by drug developers in pharma and biotech that CaMKII is not a viable therapeutic target. Off-target actions of CaMKII inhibition on learning and memory have been a major concern,” Dr. Anderson said.
More research needed
After reviewing this study, Dr. Stephen Tang, a board certified cardiac electrophysiologist at Providence Saint John’s Health Center in Santa Monica, California, who was not involved with this research, told Medical News Today it was “very exciting” to hear about new potential targeted therapies for genetic arrhythmia syndromes, such as catecholaminergic polymorphic ventricular tachycardia.
“This is an inherited genetic condition that affects calcium release in the heart and often leads to dangerous ventricular arrhythmias. It usually manifests in adolescence and can lead (to) syncope and sudden death. Our current management is very limited and is intended to control the disease, not target the underlying cause,” he explained. “
Dr. Tang commented he always approaches these small animal studies with caution.
“It is a promising proof of concept but involves animals — in this case, mice — and not humans. It is done in a lab and does not always reflect real-life conditions. Certainly, while it shows promise, there needs to be much larger studies (that) will need to show efficacy and safety in both animals and humans to be considered for clinical use,” he said.
Medical News Today also spoke with Dr. Sameer Jamal, a clinical cardiac electrophysiologist and program director of the cardiovascular diseases fellowship at Hackensack University Medical Center, who was also not involved with this research. Dr. Jamal said he was excited and encouraged to hear about this study, as it implies a potential for innovative medicines that will help us better treat cardiac arrhythmias.
“Although this study shows promise, prior use of these agents suggests potential issues (in particular) with toxicities and cognition. Continued evaluation in more carefully conducted, patient-centered settings will hopefully corroborate positive results and mitigate concerns regarding side effects,” he added.
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