Family raises millions for treatment of sons’ rare and fatal neurological disorder
Canavan #Canavan
When Jennie and Gary Landsman learned that their sons, Benny and Josh, had Canavan disease, a rare genetic neurological disorder characterized by the degeneration of white matter in the brain, they were stunned to learn there was no treatment.
“When they told me that our kids had a fatal disease and there was nothing that could be done — that was even worse than the diagnosis,” Landsman told TODAY. “(The doctor said) ‘There’s nothing you can do. Just go home and make them comfortable,’ and that’s the most horrible thing that could happen as a parent.”
The Landsmans refused to accept this. They found a team that had been developing a potential gene therapy for Canavan. But the researchers admitted their project had stalled: They needed millions of dollars to test the treatment. Since 2017, the Landsmans and other families have contributed to raising $5 million to bring this gene therapy to patients.
Benny, 4, is the first child to receive it. While the family’s excited about what this means for their children, they hope this also allows other families to avoid the chilling prognosis they heard.
“To know that people won’t have that visit any more, there won’t be that conversation where doctors will say, ‘OK, your kid has this terrible, terrible disease, but there’s something you can do’ — that’s huge,” Landsman said.
Missing milestones showed something was wrong
At first Benny seemed like any other baby, but then Landsman noticed he wasn’t meeting milestones.
“I started to get a little bit concerned when Benny wasn’t sitting up on his own,” she told TODAY in 2017. “Up until then he had been developing normally.”
While her pediatrician and others told her that Benny was healthy and children develop at a different pace, tests showed that Benny had nystagmus, rapid eye movements. Still, the ophthalmologist thought he was fine.
But Landsman knew something was wrong. She took him to several neurologists and finally one ran blood and urine tests. Benny’s urine contained the telltale sign of Canavan disease, where a missing enzyme causes the brain’s white matter to degenerate until it becomes spongy, causing missed milestones, cognitive disabilities and death by age 10, in many cases. It’s genetic and occurs commonly in the Ashkenazi Jewish population (Landsman was tested and told she carried no genetic diseases, but this was likely a false negative). There is no cure.
“It’s subtle at first, so it doesn’t raise alarm bells right away and then it gradually becomes clear that something’s going wrong and eventually it progresses toward paralysis, problems like inability to swallow,” Dr. Robert Lober, a pediatric neurosurgeon at Dayton Children’s Hospital, who is involved in the gene therapy clinical trial, told TODAY. “It can be a terrible progression towards death.”
When Benny’s doctor explained that there was nothing that could be done for him — or his younger brother Josh, who was diagnosed at just one-month-old — the Landsmans started researching. That’s when they found the gene therapy developed by Dr. Christopher Janson, at the Clinical Neuroscience Institute in Dayton, and Paola Leone, the director of the Cell and Gene Therapy Center at the Rowan University School of Osteopathic Medicine in New Jersey. But the researchers needed $1.2 million for a clinical trial.
So, the Landsmans set up a GoFundMe and raised that money. But then more money was needed.
“The trial ended up costing over $5 million dollars. Other families joined forces with us to raise money in Europe as well as in the U.S. and we opened our charity,” Landsman said, adding that they started an organization, the Cure Canavan Fund, to raise funds and advocate for the disease.
When the trial finally was approved to start, Landsman felt relief.
“It feels very very surreal. I almost feel like I’ve been working for so many years and it feels almost like a dream,” she said. “I can’t believe we’re actually here.”
Gene therapy and hope
Benny, 4, and Josh, 3, are “beautiful, happy children.” Because Benny was diagnosed later, he lost more abilities. He uses a feeding tube but eats for pleasure by mouth. Josh can still eat without a G-tube. Josh can roll over while Benny can’t. Josh maintained more ability because the family focused on early intervention.
“Any kind of skills Benny learned was in the first five months of life and then just plateaued and never learned anything new,” she said. “With Josh we got specialists in from birth … and pushed him to learn things that were inappropriate for his age.”
They taught Josh to sit up or roll earlier in the hopes he would retain these skills.
“We hoped that he would be able to maintain them in some way and it was partially true,” she said. “He has a little bit more muscle control than Benny.”
But the Landsmans appreciate time with their children instead of focusing on what Canavan might do.
“The survival tactics of these past three years have been not to think of the big picture and live day-to-day with them and enjoy each day. So, on a day-to-day basis, they are wonderful, happy, sweet kids who need a lot of extra care,” Landsman said. “When you look at the big picture, it is scary, thinking of the degeneration of their condition and what that means.”
Benny became the first patient to receive the gene therapy on April 8 and if all goes well, Josh will be the second child in the trial. The researchers remain optimistic.
“This is a good candidate for a trial of gene therapy because there’s no cure for it, but we know exactly what the problem is,” Lober said. “Canavan is due to the genetic loss of a specific enzyme in the brain that processes a metabolite. This metabolite called NAA starts to build up and that’s actually what causes the degeneration of the white matter.”
The therapy is in a viral vector that delivers the enzyme to the brain. Lober inserts four holes into the skull to deliver the therapy directly into the cerebral fluid. The researchers hope that the study will show that gene therapy decreases the metabolite that turns the white matter spongy, leading to less degeneration. If it works, these children would be able to relearn some skills and learn new ones.
“We are incredibly hopeful,” Lober said. “We’re obviously going to learn a lot that we didn’t know.”
While it’s too soon to know if Benny’s therapy worked, Landsman was pleasantly surprised by how well he recovered.
“He’s having an MRI one month post-op and they expect to see full enzyme activity,” she said. “Since the surgery, we have had the best of Benny. He’s been in a great mood. He’s been so responsive. He’s been so playful and wanting to do things and wanting to eat … The quality of his life this month is really beautiful and very unexpected.”