What is Long QT Syndrome (LQTS)?
Long QT Syndrome is a heart signaling disorder that can cause fast, chaotic heartbeats (arrhythmias), affecting an estimated 1 in 7000 people in the United States. Often undiagnosed, it is believed to result in 3,000 to 4,000 sudden deaths in children and young adults each year in the United States and Canada.
Long QT Syndrome (LQTS) is a genetic disorder that causes an elongation between the Q and T waves during a heart beat. The lengthening of these waves can cause unexpected and life-threatening arrhythmias. These unexpected arrhythmias are generally in response to exercise and stress.
Heart muscle cells have tiny pores called ion channels that open and close to let a variety of electrically charged molecules, such as sodium, calcium and potassium, pass to and from the intracellular space. These molecules are what generate the electrical activity and contraction of the heart. There are many different subtypes of LQTS, the most common types are LQTS 1, 2, and 3.
Current treatments for LQTS include:
Avoiding stressors, such as strenuous physical exercise or startling noises
Increasing potassium intake at doctor's discretion
Taking beta-blockers
Inserting an Implantable Cardioverter-Defibrillator (ICD)
Side effects of beta-blockers include fatigue, impotence, reduced exercise tolerance, cold hands, dizziness and shortness of breath. If beta-blockers fail as treatment, the patient may undergo surgery to insert implantable cardioverter defibrillator (ICD). Side effects of ICD include inappropriate shocks, potentially life threatening infection, anxiety, depression and PTSD.
Our focus on future LQTS Treatments:
SGK1 (Serum/Glucocorticoid Regulated Kinase 1) is a serine/threonine protein kinase that plays an important role in cellular stress response. This kinase activates certain sodium, potassium and chloride channels, suggesting an involvement in the regulation of processes such as cell survival and neuronal excitability.
As SGK1 is involved in regulation of sodium channel in cardiac cells, any over-activity of this kinase function recapitulates Long QT Syndrome and is associated with heart arrhythmias. Data suggests SGK1 is a prime target for shortening action potential duration (APD) in LQTS Types 1, 2, and 3, which covers approximately 90 percent of all LQT Syndrome genotypes.
SGK1’s neuronal excitability and its effect in action potential morphology (APM) of cardiomyocytes has captured our attention.
At Thryv Therapeutics (previously LQT Therapeutics), our team is working hard to develop a potent SGK1 inhibitor.
About Thryv Therapeutics
Thryv Therapeutics Inc., previously called LQT Therapeutics Inc. is a privately owned company based in Montreal, Quebec, Canada. We have been pioneering a precision medicine approach to treat Long QT Syndrome via SGK1 inhibition since 2019 and have since evolved our portfolio to include the treatment of resistant and rare cancers. The development of SGK1 inhibitors represents a novel approach to target treatment-resistant cancers, and complement existing therapies. This strategic evolution has secured an additional US$15M financing fuelling Thryv to complete a proof-of-concept study for LQTS, and submit an IND for the treatment of resistant cancer.
