In 2016, when Susannah Rosen was two and a half years old, her parents, Luke Rosen and Sally Jackson, noticed during bath time that something wasn't right. When Sally asked Susannah to playfully kick her legs in the water, she couldn't do it.
“For our first child, if it was a bee sting, we'd run to the emergency room, right? But we thought, she's our second child, you know? She'll catch up on her own… but she didn't,” Luke said. “When we found out he couldn't kick, we went to the hospital.”
Luke and Sally lived with their two children in New York City. Luke had a thriving career as an actor and writer, and Sally worked as a chef's assistant.
Luke said Susannah didn't have great balance when she was little and needed help walking, common characteristics of a child learning a new milestone. But as time passed, the gap between Susannah's development and that of her peers began to widen.
Sally Jackson, Luke Rosen and their daughter, Susannah Rosen
“He was couch surfing and crawling around the apartment at an age when little kids usually go running,” Luke recalled. When she attempted to walk, Susannah walked with a wide stride and appeared unsteady and uncoordinated, which was often a symptom of an underlying problem.
Susannah was diagnosed with a mutation in her KIF1A gene. The KIF1A gene is named after an important molecular motor protein it creates that is vital for brain function. Mutations in this gene cause the KIF1A-associated neurological disorder or KAND. When Susannah was diagnosed, Luke and Sally were told that 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!” Lucas said. “[But] It's not good. “The function that that gene takes on emits this really toxic protein element that slowly kills the nerves in your brain and kills the nerves throughout your 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. Additionally, many experience other symptoms, ranging from diarrhea and constipation to kidney problems. Experts say no two patients are affected in the same way, making the disorder very difficult to properly diagnose. According to KIF1A.org, approximately 1 in 4 of people diagnosed with KIF1A mutations were originally misdiagnosed with cerebral palsy.
Sally, Luke and Susannah out for a walk.
Courtesy: The Rosen Family
At the time of Susannah's diagnosis in 2016, there were no treatments for KIF1A, no clinical trials underway, and no literature to rely on for answers. The Rosens were told that Susannah probably wouldn't be able to walk and would probably suffer seizures.
“So there were a lot of tears in that room,” Luke said. “That was the beginning of our incredibly scary new normal.”
Susannah's doctor, Dr. Wendy Chung, a member of the CNBC Advisory Board, told the Rosens they had five years to find a treatment for Susannah before it was likely too late. He recommended Luke and Sally try to find 100 patients with the same diagnosis as Susannah so they could begin to better understand the disease and how it progresses.
CNBC heals Susannah Rosen and Dr. Wendy Chung
Courtesy: The Rosen Family
Luke and Sally founded the KIF1A.org Foundation shortly after Susannah's diagnosis. They hoped that by connecting with other families living with KAND, they could create a large enough patient population to start research that could eventually lead to the discovery of a treatment. Today, the foundation has been able to connect 700 families in hopes of racing together against the clock.
“One of the things we realized about KIF1A is that it's not as rare as we might think,” Chung said in a recorded interview with KIF1A.org. “We can see over the last three years that we have seen 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 nanorare diseases and provides treatments to patients free of charge 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 in hospital for ASO treatment.
Courtesy: The Rosen Family
“The FDA defines rare diseases as a patient population of 200,000,” Crooke said in an interview with CNBC. “But now we know that there are many, many pathogenic mutations that cause disease in many fewer patients… And our focus is on these patients, because they have no hope. You can imagine the isolation, the despair and the lack of information available when you are one of the 30.”
Crooke estimates he has personally spent $10 million since 2020 on developing new drugs and treating patients, a fraction of the amount the foundation has spent, he said. Patients with the same mutation can be treated with the same drug, 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 has 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 waiting list and n-Lorem will soon begin treating the organization's 40th patient, he said.
But when the Rosens heard about the work 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 the first n-Lorem patient to be treated with an ASO therapy developed by the foundation.
ASO therapy is a spinal procedure that removes fluid and replaces it with medication that attacks the genetic mutation. In Susannah's case, 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 several things: prevent the production of a disease-causing protein, make a better protein, or make a protein that isn't made in enough quantity.”
After Susannah's second dose, Luke began to notice a difference in Susannah's behavior, he said.
“One morning after getting treatment, we were sitting eating breakfast and I thought, 'Something's wrong,'” Luke recalled. “But it wasn't. It was the fact that everything 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's something that means a lot to us. She still has her challenges and problems, but that tremor goes away, where we can have breakfast together… that's when I knew the medication was working.”
The Rosen family enjoys a meal together.
Courtesy: The Rosen Family
Susannah has been receiving ASO treatments for three years and the Rosens said they are grateful for the time she has given them. But they know the road ahead for Susannah will likely continue to be difficult.
“We fear the disease is catching up to the treatment. She is regressing in some ways, and we just wish we had received this treatment five years ago,” Luke said. “The next child [to receive the same treatment] I will be younger and the treatment will reach every cell in the brain… I know. Our girl is a pioneer. It is both heartbreaking and partly heartwarming. “She's amazing and tough as nails.”
For more information on KIF1A-associated neurological disorders, see the Luke and Sally Foundation, KIF1A.org.
