According to a publication from Fierce Biotech, researchers from Boston Children’s Hospital have created a new gene therapy technique they believe could provide benefits to patients with inherited forms of arrhythmia or other irregular heartbeat conditions.
In particular, researchers focused on catecholaminergic polymorphic ventricular tachycardia (CPVT), a rare but potentially serious form of arrhythmia triggered by physical or emotional stress.
About Catecholaminergic Polymorphic Ventricular Tachycardia
CPVT is rare — thought to occur only about once in every 10,000 births. However, accurate rates of occurrence are difficult to determine due to varying degrees of medical care quality in many countries around the world.
Researchers have identified two genes as known to be associated with CPVT — RYR2 and CASQ2. In healthy individuals, these genes are responsible for coding the production of proteins that play an essential role in maintaining a stable heartbeat. Myocytes, muscle cells of the heart, contract and relax in a coordinated fashion to produce a heartbeat. This contraction process is largely controlled by the flow of calcium molecules into and out of the myocytes.
RYR2 and CASQ2 (the proteins associated with RYR2 and CASQ2, respectively) both regulate calcium activity within the myocytes. Mutations to RYR2 or CASQ2 can disrupt healthy myocyte activity, especially in high-stress situations. RYR2 mutations are responsible for about 50% of known cases, while CASQ2 mutations are only thought to be responsible in one or two per cent of cases.
If untreated, or worse yet, undiagnosed, CPVT can lead to potentially fatal cardiac arrest. Some suspect CPVT to be the cause of many otherwise unexplained sudden deaths in children and young adults.
Tissue and Animal Models Show Enzyme Inhibitor’s Promise
Researchers at Boston Children’s Hospital created a tissue model in a lab to simulate a CPVT-affected heart. During their research they found that an enzyme called CaM kinase (CaMKII) acts on RYR2 proteins to stimulate excessive calcium intake into the myocytes. The result is an overactive, irregular heartbeat. In non-human studies, the researchers found that CaMKII inhibitors could effectively reduce myocyte calcium intake.
Because CaMKII acts on a diverse collection of heart cells, researchers want to be cautious when proceeding to human testing. Researchers plan to refine and test the CaMKII inhibitor treatment in larger animal studies before testing in human CPVT patients — meaning it could be years before this highly experimental treatment is made available to them (if it ever is). Despite that, the research is welcome to a community whose treatment options are currently limited to only beta-blockers and surgery.
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