Audentes is exploring opportunities to outlicense the CPVT program to continue to advance this important gene therapy.
About CASQ2-related CPVT
CASQ2-related Catecholaminergic Polymorphic Ventricular Tachycardia is an inherited disease caused by mutations in the CASQ2 gene. CASQ2 encodes a protein called calsequestrin 2, which plays a key role in the physiology of calcium release in cardiac muscle cells, and which is required to maintain normal heart rhythm.
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is characterized by abnormal ventricular heartbeats (arrhythmias) that can cause dizziness and fainting and that can progress to cardiac arrest and sudden death. These arrhythmias are precipitated by exercise or stress, which place considerable limitations on activities of daily living, and introduce ongoing anxiety about the risk of arrhythmia into the lives of patients and their caregivers. If suspected by the treating physician, CPVT can be diagnosed by exercise electrocardiogram (ECG) testing, with confirmation of the specific gene defect through genetic testing. It is estimated that more than 6,000 people globally have CPVT caused by a mutation in CASQ2. There are additional types of CPVT caused by other gene mutations. Current treatments for ventricular tachycardia are considered inadequate for CASQ2-CPVT and there are no therapies currently approved specifically for the treatment of this disease.
For more information about CPVT, please visit the links below.
Community Support & Resources
Where can you find information and support for CPVT?
Below are some helpful organizations and resources. Each of them offers something unique to the CPVT communities around the world.
The United Kingdom
Learn about patients and families affected by CPVT.
Age 11* | California, USA
The Flores family prepares themselves for a competitive dance-off. First up is Isabella, or Bella, and her younger brother, Milan. They grip their Wii controllers and agree on a song. The music begins. In a flurry of energy, Milan and Bella imitate each movement on screen, following every nuance of the dancing figures as best they can. As arms begin to flail and legs extend, concentration thickens. Their parents cheer them on from the couch in their living room, taking much joy in watching their kids twist about amicably. Bella and Milan are both racking up points, seemingly more motivated to beat their own personal records than each other. The three-minute song feels remarkably long and they both breathe heavily, trying to keep up with the high-paced tempo. As the song finishes, Bella spins around with an incredibly wide smile on her face. She hands off the controller to her mother for the next round and plops down on the couch to catch her breath, pleased with her performance and her victory.
Bella’s dancing abilities are just the start of her creative passions. After several rounds of dancing, Bella grabs a notebook filled with colorful drawings, handwritten poetry, and songs that await new melodies. Much of her writing speaks to her ideals: expounding inclusivity in her world, that no matter how different, everyone deserves an equal chance. She writes about friendship, the power to be yourself, and the bonds that hold people together. At 11 years old, Bella is already an avid photographer. Her photo collection highlights her fascination with the natural world. She went to a photography summer camp and took dozens of shots around scenic Balboa Park, San Diego. Her perspective accentuates the minutiae, with ample attention paid to the shape of each leaf, the texture of each stick, in contrast to the idyllic backdrop of the park. In her approach, the attention to detail expresses a greater appreciation for all living things.
“Honestly—and this keeps me going throughout the day without falling apart—I feel that Isabella is meant to be here,” says her mother, Rachel. “She has a greater purpose that perhaps we don’t even know yet. She doesn’t probably know either.” The relative normalcy that has settled into the Flores’ household these days is remarkable in the context of Bella’s condition, a rare cardiac disorder called Catecholaminergic polymorphic ventricular tachycardia, or CPVT.
CPVT is extremely difficult to diagnose and is most often unknown until a life-threatening episode occurs. Such events are triggered when an increase in adrenaline, from either acute emotional or physical stress, causes a specific arrhythmia in the heart, leading to potential cardiac arrest. “It is an invisible disease,” says Rachel. “Everything looks absolutely perfect.” The heart appears to function perfectly when it’s not arrhythmic, which gives a very small window in which diagnosis can occur. “We were so lucky to find out. I mean, more than 90% percent of the people never know until it’s too late,” says her father, Rolando. Through a series of miraculous events Bella is here today and has transformed her family into more than just caretakers, but advocates, who are raising awareness in their community about the prevalence of this life-threatening condition.
Bella’s episodes began when she was seven years old, during a summer visit to SeaWorld. She and her mother decided to ride a roller-coaster together. “The only thing I remember is that it pulled us back, and then shot us forward,” says Bella. Within moments of the ride beginning, Bella passed out cold in the seat, next to her mother. Fearing a spinal cord injury, Rachel, who works as a nurse, stabilized Bella’s head as best she could for the remainder of the ride. After pulling her unconscious body from the roller-coaster seat, Bella would awake in her mother’s arms, apparently unscathed. “We took her home after the SeaWorld episode and we didn’t think anything more than being scared had caused her to faint,” says Rachel.
Things returned to normal that summer, and Bella went back to being her exuberant self. “I would’ve never imagined in a million years there was anything going on,” remembers Rachel. Except two weeks later, Bella had a similar episode at summer camp. Again, she passed out, this time in the presence of her brother and friends, with no apparent cause. Rachel listened to her instincts and made the call to bring Bella to the hospital for observation. “Her EKG was normal. All her labs were normal,” recalls Rachel. The doctors postulated that Bella was probably just dehydrated, but Rachel and Rolando refused to go home without more conclusive information. “I said no. This happened twice now. Something is going on.” The hospital ran even more tests: EEG, electrocardiogram, an MRI, and more blood work. Still, the couple was not satisfied. “We insisted on having an event monitor,” says Rachel. “We wanted it for an entire month, because she had been symptomatic two weeks apart.”
That month with the monitor had nearly passed when Bella found herself in the school nurse’s office crying. She felt like there were “pins and needles” throughout her body. Rachel arrived and took Bella to the hospital for a third time. Yet again, under observation, the doctors could find nothing wrong. They suggested that Bella was having panic attacks, and perhaps had an anxiety disorder. However, as the family was getting ready to leave the hospital, the heart monitor company called them. “We were being discharged,” recalls Rachel. “And they called and were like, ‘you’re not going anywhere.’” An arrhythmia was detected in Bella’s heart from afar. Her EKG was sent to a doctor who was filling in for the regular pediatric cardiologist. As luck would have it, a week prior, he attended a seminar that specifically talked about CPVT. He immediately recognized the rhythm. The cause of Bella’s fainting episodes was no longer a mystery.
“The diagnosis was absolutely devastating and breathtaking,” declares Rachel. “It was the most painful thing I have ever experienced.” Despite the severity of diagnosis, Rolando and Rachel realized how fortunate their situation was. “It was scarier not to know, then to know,” says Rolando. To this day, they remain in awe of the number of events that occurred in total synchronicity in order to save their daughter’s life. “I hold onto that thread of optimism [knowing] that we could’ve lost her so many times,” says Rachel. “If we didn’t lose her then, then we’re certainly not going to lose her now.”
“I take beta-blockers now,” explains Bella. “They are pills that help my heart stay relaxed.” Since diagnosis, Bella started taking beta-blockers and antiarrhythmics to avoid future cardiac events, as well as monthly trips to the hospital for cardiac tests, but these do not entirely void the risks. In the past four years, she’s had to develop a sense of what amount of physical exertion is safe. “I take a lot of breaks in PE class,” says Bella. “I stop when I feel like I’m tired, or when my heart is beating too fast.”
At this point, her parents still make the bulk of the decisions about which activities are safe and which are not. “It’s such a finesse of a dance,” says Rachel. “We don’t want to leave her out of things, because that causes emotional stress.” Rolando and Rachel support Bella in what she wants to do—challenging herself and growing as a young woman—while creating an environment that is safer for her, if an episode were to occur. Still, they operate with a certain base-level of cautious optimism. “You never know whether the decision you make is the right one or not,” explains Rolando. “Our goal is just to make sure that she is happy.”
One tract they are all sure about is advocacy. Bella and her entire family are fighting to raise awareness, not only about CPVT, but of the need for more education around life-saving skills. Rachel helped facilitate CPR and AED trainings at Bella’s school for the past three years. “Rachel has worked tremendously with the school,” says Rolando. “It is the only school in California that is heart-safe certified.” Bella is exuberant about sharing this knowledge too. “We trained over 300 people last year. It was very cool,” says Bella. These are crucial skills, not just for Bella’s sake, but for the community at large. “Imagine the kids who’ve been doing this since kindergarten,” says Rolando. “Years later, they’re not going to be afraid. They will save lives.”
“All of my friends know that I have a heart condition,” says Bella. “Some of my friends know my specific condition, but they don’t treat me different.” Bella’s amicable glow seems to naturally attract friends, while her life experiences make her an intrinsic caregiver. She recently attended her first school dance—a hallmark of approaching adolescence—and one of her friends was feeling sick. “I spent most of the dance with her,” she says. “I didn’t want her to feel alone.” Her ability to nurture others is instantly apparent and is sure to serve her and her friends well in the coming years.
Soon Bella will be making more of her own choices, and her parents are setting the stage for that transition. “We’ve been trying to explain to her what gene therapy is, and what is potentially coming,” says Rolando. “We try to explain to her how the heart works, but so far, we still make all the decisions.” He imagines in a few years, Bella might be eligible for a clinical trial, a decision she will ultimately have to make.
With love and precautions Bella and her family hope to continue the fight to raise awareness about CPVT in their community, and to retain the balance in their lives that every family needs. “I feel that I can do whatever I want, as long as I know when to stop,” says Bella. Her astounding calmness in the midst of such high stakes speaks volumes to what she will accomplish in the future. “She’s here for a higher purpose,” states Rachel. “She’s gonna do something.”
For now, Bella is mastering the art of making fish and chips, as she helps cook dinner for her family. “I try hard to get each piece totally covered,” she says, as she skillfully rolls the fish through the bread crumbs. Rolando cracks open a jar of homemade salsa and mouths begin to water. The family sits down around the table together and shares their meal. Bella inspects her handiwork, meticulously searching for the right piece of fish, the most golden, flaky, and perfectly cooked. She’s found it, and she’s ready to eat—self-satisfaction beaming from her widening grin.
*Isabella was 11 years old when these photos were taken in 2017.