In 2016, when Susannah Rosen was 2½ years old, her parents, Luke Rosen and Sally Jackson, noticed during bath time that something wasn’t right. When Sally prompted Susannah to playfully kick her legs in the water, she wasn’t able to.
“For our first kid, if it was a bee sting, we would run into the emergency room, right? But we were like, she’s our second kid, you know? She’s gonna catch up on her own … but she didn’t catch up,” Luke said. “After we found out she couldn’t kick, we went to the hospital.”
Luke and Sally were living with their two kids in New York City. Luke had a thriving career as an actor and writer, and Sally was working as a chef’s assistant.
Luke said Susannah didn’t have great balance as a toddler and needed assistance walking, common characteristics of a child learning a new milestone. But as time went on, the gap between Susannah’s development and that of her peers started to widen.
Sally Jackson, Luke Rosen and their daughter, Susannah Rosen
“She was couch surfing and army crawling around the apartment at an age when toddlers typically take off running,” Luke recalled. When she tried to walk, Susannah had a wide gait and appeared unsteady and uncoordinated, often a symptom of an underlying problem.
Susannah was diagnosed with a mutation in her KIF1A gene. The KIF1A gene gets its name from an important molecular motor protein that it creates that is vital to brain function. Mutations in this gene cause KIF1A-Associated Neurological Disorder, or KAND. When Susannah was diagnosed, Luke and Sally were told the mutation in her KIF1A gene was causing a “toxic gain of function.”
“When I heard that, I thought, oh, ‘gain of function.’ That’s good!” Luke said. “[But] it’s not good. The function that that gene gains gives off this really toxic element of protein that slowly kills the nerves in her brain and kills the nerves in her whole body.”
More than 90% of patients diagnosed with KAND have developmental delays and intellectual disabilities, more than 80% have vision loss or impairment, and more than 40% have seizures. In addition, many experience other symptoms, ranging from diarrhea and constipation to kidney problems. Experts say no two patients are affected in the same way, which makes the disorder very difficult to properly diagnose. According to KIF1A.org, approximately 1 in 4 of those diagnosed with KIF1A mutations were originally misdiagnosed with cerebral palsy.
Sally, Luke and Susannah on a stroll.
Courtesy: The Rosen Family
At the time of Susannah’s diagnosis, in 2016, there were no treatments for KIF1A, and no clinical trials underway or literature to lean on for answers. The Rosens were told that Susannah probably would not be able to walk and would likely suffer from seizures.
“So there were a lot of tears in that room,” said Luke. “That was the beginning of our incredibly new and terrifying normal.”
Susannah’s physician, Dr. Wendy Chung, who is a CNBC Advisory Board member, told the Rosens that they had five years to find a treatment for Susannah before it would likely be too late. She recommended Luke and Sally try to find 100 patients with the same diagnosis as Susannah so that they could begin to better understand the disease and how it progresses.
CNBC Cures Susannah Rosen and Dr. Wendy Chung
Courtesy: The Rosen Family
Luke and Sally started the KIF1A.org Foundation shortly after Susannah’s diagnosis. They hoped that by connecting with other families living with KAND, they could build a patient population large enough to start research that could eventually lead to a treatment discovery. Today, the foundation has been able to connect 700 families hoping to race against the clock together.
“One of the things we realized about KIF1A is that it’s not nearly as rare as we might think it is,” Chung said in a taped interview with KIF1A.org. “We can see just over the past three years that we’ve been watching the numbers grow.”
Those efforts eventually led them to the n-Lorem Foundation. Launched in 2020 by Ionis Pharmaceuticals founder and CNBC Advisory Board member Dr. Stanley Crooke, n-Lorem is a nonprofit organization that develops antisense oligonucleotide, or ASO, therapies for patients with nano-rare diseases and provides the treatments to the patients for free for life. Nano-rare is a term coined by Crooke to describe diseases that are extremely rare — affecting between one and 30 people worldwide.
Susannah Rosen at the hospital for her ASO treatment.
Courtesy: The Rosen Family
“The FDA defines rare disease as a patient population of 200,000,” Crooke said in an interview with CNBC. “But we now know that there are many, many pathogenic mutations that produce disease in far fewer patients … And our focus is on these patients, because they have no hope. You can imagine the isolation and the desperation and the lack of information that’s available when you’re one of 30.”
Crooke estimates he has personally spent $10 million since 2020 on developing new drugs and treating the patients, a fraction of the amount the foundation has spent, he said. Patients with the same mutation can be treated with the same medicine, but if n-Lorem needs to develop a new treatment, the average cost is $1.2 million, he said.
Since the foundation’s launch, it’s had more than 400 rare disease patient applicants, of which it has been able to accept about 200, Crooke said. Once accepted, the patient is added to a waitlist, and n-Lorem will soon begin treatment on the organization’s 40th patient, he said.
But at the time the Rosens learned about the work that Crooke was doing, n-Lorem was just getting started. Chung submitted an application for n-Lorem to develop a treatment for Susannah, and Susannah became n-Lorem’s first patient to be treated with an ASO therapy developed by the foundation.
ASO therapy is a spinal procedure that pulls out fluid and replaces it with the drug that targets the gene mutation. In Susannah’s case, the ASO therapy allows for normal protein production.
Sally Jackson and her daughter, Susannah Rosen, in a hospital bed
Courtesy: The Rosen Family
“It’s genetic medicine,” Crooke said. “So we take the genetic code directly and design a relatively small molecule, 18 to 20 genetic letters with that genetic ‘ZIP code’ that will direct it to the RNA in the cell that we want it to bind to. And then we can design the ASO to do various things: to prevent the production of a disease-causing protein, produce a better protein, or produce a protein that’s not being produced in enough quantity.”
After Susannah’s second dose, Luke started noticing a difference in Susannah’s behavior, he said.
“One morning after she had received treatment, we were sitting at breakfast, and I was like, ‘Something is wrong,'” Luke recalled. “But it wasn’t. It was the fact that it was quiet and we were able to look at each other. Her tremor was gone. That’s not an FDA-approved outcome measure or an end point, but it is something that just means the world to us. She still has her challenges and problems, but just that tremor going away, where we can have breakfast together … that’s when I knew that the drug was working.”
The Rosen family enjoy a meal together.
Courtesy: The Rosen Family
Susannah’s been receiving the ASO treatments for three years, and the Rosens said they’re thankful for the time it’s given them. But they know the road ahead for Susannah will likely remain a difficult one.
“We’re afraid the disease is catching up to the treatment. She’s regressing in ways — and we just wish we had gotten this treatment for her five years ago,” Luke said. “The next kiddo [to receive the same treatment] will be younger, and the treatment will get into every brain cell … I know it. Our gal is a pioneer. It’s both heartbreaking and in part heartwarming. She’s amazing and tough as nails.”
To learn more about KIF1A-associated neurological disorders, see Luke and Sally’s foundation, KIF1A.org.
