Mary Saladino spends most of her days holding her son in her arms while he violently seizes, whispering to him as she frantically tries to save his life. Nearly every day she witnesses her baby waver on the brink of death, not breathing and often paralyzed.
Her 3-year-old son, Henry, suffers from alternating hemiplegia of childhood, or AHC, a rare neurological disorder whose patients are referred to as “human time bombs.” At any moment, Henry can stop breathing, have a life-threatening seizure or become paralyzed – and there’s no way to know when it will happen or if he will survive.
No treatment or cure exists for AHC, which affects one in a million people globally, according to AHC expert and neurologist Dr. Kathryn Swoboda, and families of patients with this unpredictable disease never stop watching for signs of an oncoming episode. As soon as it strikes, they must act quickly to administer lifesaving measures.
“When you’re feeling that fear you’re going to lose your child, you have to be thinking what would I want to give him as his mom if this is it? I want him to hear how much we love him, but also oh my God, I have to save him, what’s his oxygen level? Do I need to resuscitate him? Did I give the first dose of rescue medication?” Saladino told CNN. “It’s an unbelievable amount of trauma and it’s going to happen over and over again, no matter what we do, until we develop this treatment.”
Despite its name, AHC does not affect people only during childhood. It only worsens with age, according to Swoboda, with patients often losing most of what they learned as children, such as walking, talking and eating independently.
In 2022, Mary and her husband Anthony launched the nonprofit foundation For Henry to raise $3 million for a genetic treatment that, if successful, could be the first to treat AHC and pave the path for others living with the disorder to receive treatment.
Through their foundation and GoFundMe fundraiser, the Saladinos are raising the remaining $2.5 million needed to design from scratch an antisense oligonucleotide, or ASO treatment, which would knock down the toxic impact of a genetic mutation that is causing the dysfunction in Henry’s brain.
The family is racing to develop and administer the treatment before Henry’s brain is irreversibly damaged during one of his spells. This risk increases every time Henry survives another seizure in which he stops breathing on his own – sometimes for up to 15 minutes – or experiences paralysis that can last for days at a time, his neurologists say.
“We have reached a point where, as a clinician, I am unable to provide Henry with a better option to try and prevent him from having more seizures or episodes,” Dr. Christelle Achkar, Henry’s neurologist, told CNN. “Henry is one of those children who are at higher risk of premature death due to their condition, and if they survive, there is always a concern of potential for severe regression. This is his only chance.”
If it works, according to Swoboda, this would also establish proof of concept that this type of therapy might be developed to treat several other neurological syndromes caused by mutations in the same gene – including a rare type of Parkinson’s disease.
“While this is about Henry, it is also about many other patients whose lives can be impacted by this therapy,” Achkar said.
What AHC does and how an ASO treatment can help
In one instant, Henry is dancing and singing as his parents dress him in pajamas. Suddenly, he goes limp, half of his body paralyzed and the other half violently convulsing as his parents rush to administer drugs and oxygen.
Many things can trigger the episodes, such as a bath or sunlight, but especially moments of stress or excitement. Holidays, birthdays and even play dates can be too overwhelming, Henry’s parents say, and they have to watch him transition from delight to suffering at their happiest moments.
“AHC is the worst disease I have ever worked with in terms of the level of stress, for both parents and physicians. Episodes can strike at any time, and it is not readily clear when an episode is going to be catastrophic and require a hospital visit or urgent intervention,” Swoboda, Henry’s former neurologist, told CNN.
“They have to reconsider everything,” she added. “You can’t take them to a mall with bright lights and excitement. If you take them to a swimming pool and it has cold water, they might go down. If they get too excited before their therapist is going to come over, they get paralyzed and can’t do their therapy.”
AHC can be caused by 163 different mutations in the ATP1A3 gene, but three mutations, including the one that Henry has, account for 75% of cases, according to Swoboda. The ATP1A3 gene encodes a sodium potassium pump critical for maintaining a normal electrical gradient in all neurons in the brain. It is vitally important.
“It’s like your power goes off in your house and you have a backup generator, but your backup generator isn’t working so well,” Saladino said. “We see the disease manifest at moments when Henry’s tank is running low. It could be when he’s too hot, tired from climbing upstairs, or he’s hungry or his brain was working too hard during therapy.”
Because of the faulty pump, Swoboda says, having AHC is like having seven neurological conditions at once: paralysis similar to a stroke, seizures like epilepsy, low muscle tone like cerebral palsy, movement problems like Parkinson’s, neurodegeneration like Alzheimer’s, behavioral issues similar to attention-deficit/hyperactivity disorder and behavioral challenges like autism.
Henry, who suffers from the most severe mutation, has a significant speech delay. He is able to understand everything being said to him but struggles to produce words. He also has significant gross motor and fine motor delays, meaning he can’t walk on his own and struggles to perform tasks like using utensils.
While AHC foundations are currently pursuing other strategies including gene therapy and gene editing, nothing has been developed yet and an ASO treatment is still Henry’s quickest and best chance to slow the inexorable progression of this disease, his neurologists say.
ASO’s are short strings of nucleotides that can be imagined as small strings of DNA or RNA letters that can interfere with RNA processing. They work by either helping the body create missing good protein or by knocking down toxic protein, according to the Yu Lab, a research laboratory run by Boston Children Hospital neurologist Tim Yu.
“For his exact mutation, if you think about DNA, you have two copies of everything. He has one good copy and one abnormal copy. Not only is his bad copy improperly functioning, it’s also preventing the healthy copy from functioning properly,” said Achkar, a neurologist at Boston Children’s Hospital and an expert in designing and conducting clinical trials involving ASOs. “A knockdown ASO would target the abnormal copy of the gene, by preventing it from turning into the abnormal protein, without affecting the healthy copy.”
Henry’s current and former neurologists are optimistic that an ASO treatment could be successful in eliminating or dramatically minimizing Henry’s frequent episodes and allow him to resume a healthy and normal developmental trajectory.