Tom Cancelleri sat on his recliner for three days, unable to sleep. A laptop rested on his knees as he scrolled through everything he could find about Alexander disease.

Just days earlier, on September 13, 2021, Cancelleri and his wife had joined a Zoom call with a neurologist from Children’s National Hospital. Their son Levi, then 32 days old, had been having seizures.

“She said, ‘I have good news and bad news,’” Cancelleri recalls. “The good news is we know what the issue is with Levi and why he’s having seizures. The bad news is he has Alexander disease, and it is not treatable. Your son won’t live past two.”

Levi was their second child. They had brought him to the emergency room on August 27, 2021, when he was just over a month old. An ambulance transferred him to a pediatric ICU, where he spent six days undergoing EEGs, blood work and an MRI. No one knew what was wrong until the genetic test results came back.

“Hearing that as a parent is possibly one of the worst things that anybody can hear,” Cancelleri says. “We just kind of fell apart.”

For families facing an Alexander disease diagnosis, that moment has long been a doorway into a world of uncertainty. The disease is ultra-rare, affecting approximately one in one to three million people worldwide. There is no cure and there was no treatment that addressed the disease itself—only symptom management.

That changed on September 3, 2026.

What is Alexander Disease?

Alexander disease is a rare, progressive neurological disorder that affects the brain’s white matter. It is one of a group of conditions called leukodystrophies, which involve the destruction of myelin—the fatty covering that protects nerve fibers and helps transmit signals throughout the nervous system.

The disease is caused by mutations in the GFAP gene, which provides instructions for making glial fibrillary acidic protein. This protein is found primarily in astrocytes, specialized cells that support and nourish other cells in the brain and spinal cord.

When the GFAP gene is mutated, it leads to the overproduction and toxic accumulation of this protein. Over time, the protein clumps together into abnormal structures called Rosenthal fibers. Astrocyte function becomes impaired in multiple ways that contribute to the disease’s progression.

Symptoms of Alexander disease vary depending on age of onset. The most common form, infantile-onset, appears before age two and can include:

• Seizures
• Enlarged brain and head size (megalencephaly)
• Stiffness in the arms and legs (spasticity)
• Developmental delay
• Intellectual disability

Later onset forms of the disease may present with speech difficulties, swallowing problems, seizures, and poor coordination.

Alexander disease is inherited in an autosomal dominant pattern, meaning a mutation in just one copy of the GFAP gene is sufficient to cause the disorder. Most cases result from new mutations with no family history of the disease.

The disease is progressive and often fatal. Alexander disease often leads to death within 14 to 25 years after symptom onset.

A Discovery Decades in the Making

The road to a treatment began in a laboratory at the University of Wisconsin-Madison in the 1990s. Albee Messing, now an emeritus professor of neuropathology at the university, was studying GFAP.

When his lab, in collaboration with Michael Brenner (then at the National Institutes of Health), engineered mice that expressed too much GFAP, the animals got sick. Some died within weeks of birth. When Messing examined their brains, he found Rosenthal fibers—the same abnormal structures seen in patients with Alexander disease.

“All neuropathologists learn about Alexander disease during their training,” Messing says. “We realized that we might have stumbled on a genetic cause for at least the formation of Rosenthal fibers.”

Messing and Brenner then sequenced the GFAP gene in 13 patients with Alexander disease. They would have been happy to find abnormalities in one or two. It turned out that 12 out of the 13 patients had variants in the gene.

“It was so striking that as a genetic test it had actually moved into clinical practice before we even published our paper,” Messing says.

Before that breakthrough, the only way to confirm an Alexander disease diagnosis was to find Rosenthal fibers through a brain biopsy or autopsy. For a living patient, that meant brain surgery.

Once Messing’s team found that GFAP mutations caused the disease, a blood sample or cheek swab could be used as a source of DNA to test for the mutation.

He decided to devote the rest of his career to Alexander disease.

“It occurred to me early on that if we’re going to put that much effort into understanding it, maybe we should try to do something about it,” he says.

That meant finding a way to lower GFAP levels. Messing’s lab screened thousands of FDA-approved drugs. Nothing worked. Then, around 2013, he began collaborating with Ionis Pharmaceuticals, a company that specialized in a new kind of antisense drug. This meant that instead of fixing the protein after it was made, these drugs stopped the body from producing it in the first place.

The results in mice were dramatic. If treated early enough, the animals never developed disease.

Alexander mice, while useful for studying the disease at a cellular level, don’t get as sick as human patients. So, Messing’s lab made a rat model with the same mutation.

The rats were much sicker. They stopped growing around weaning age. By eight weeks, they were 25 to 30 percent the size of normal rats. They had problems with myelin, which the mouse model never quite captured.

Then, they tried the antisense treatment on the rats.

“I took a video of three rats,” Messing says. “One of them was a normal rat, one of them was an Alexander rat that had been treated with saline as a control, and one was an Alexander rat that had been treated with antisense.”

He sent the video to his collaborators at Ionis and asked them to identify which rat was which.

“The mutant rat looked really tiny and was staggering around the cage,” Messing says. “The other two rats looked indistinguishable.”

The mouse and rat studies together, Messing says, catalyzed the movement to shift the treatment into a clinical trial.

The Path to Zanvastro

After engineering a compound that appeared to work in both human and rodent models, the clinical trial launched in 2021 with 49 participants aged 2 and older, plus four children younger than 2 in a separate substudy.

Researchers used a 10-meter walk test as the main measure. Walking speed slows as the disease progresses, so stabilizing it would show the drug was working. In participants aged 5 and older, those who received Zanvastro maintained their walking speed over 61 weeks. Those who received the placebo declined.

In children aged 2 to 4, treated participants improved on a broader motor assessment while those in the control group declined.

On September 3, 2026, the FDA approved Zanvastro (zilganersen) for the treatment of Alexander disease in pediatric and adult patients. Zanvastro is an antisense oligonucleotide administered as an injection into the spinal canal every three months by a trained healthcare professional. It works by reducing production of the abnormal GFAP protein before it can accumulate and cause further damage.

“For patients with Alexander disease and their families, there have been no approved treatment options—only supportive care while the disease progresses,” Emily Freilich, director of the FDA’s Division of Neurology, announced in a press release. “Today’s approval is a landmark moment for this community, offering the first therapy that addresses the underlying cause of this rare and serious disease.”

The approval does not resolve every challenge. Ionis has priced Zanvastro at approximately $285,000 per dose, administered four times per year—putting the annual cost at over $1 million per patient. Access outside the United States also remains unclear, prompting End AxD and other advocacy organizations to urge Ionis to accelerate international access.

A Shift in Possibility

Families living with Alexander disease have long been told that no treatment was possible. The approval changes that—even as questions about cost and access remain unresolved.

Cancelleri’s son Levi was not eligible for the clinical trial. He had aged out of the under-two substudy before it finished enrolling. But when the Expanded Access Program opened, Cancelleri and his wife decided to try the treatment.

“It’s probably the best choice we’ve ever made,” Cancelleri says.

Levi received his first dose earlier this year and according to Cancelleri, the changes have been profound. Levi has taken his first steps. He is speaking more and his words are becoming clearer. He turned five in July.

For years, Cancelleri and his family have lived with the daily realities of Alexander disease. Levi has had between 50 and 60 seizures in his five years. Some months pass without any. Other times, he has four or five in two weeks. Illness and lack of sleep lower his seizure threshold, so Cancelleri and his wife keep constant watch.

“There’s never 10 seconds where you’re not on guard,” he says.

But Cancelleri hasn’t faced this alone. End AxD, the primary patient advocacy organization for Alexander disease, has been a lifeline for families like his. The organization is a community-led nonprofit where every board member has a personal family connection to Alexander disease. It funds research, supports families, and advocates for better treatments. In 2025, End AxD launched a grant program to provide seed funding to scientists studying the disease, overseen by a scientific advisory committee chaired by Messing himself.

Cancelleri now serves as the awareness pillar lead for End AxD, a role he took on earlier this year. His job is to raise awareness in any way he can—through poster campaigns, community videos, and media outreach. He built a tool that lets families create their own awareness posters for Leukodystrophy Awareness Month-drawing on 25 years of IT experience-and he’s working on a video project to showcase the people affected by Alexander disease.

“Awareness means making Alexander disease visible and making information easier to find, understand, and use,” he says. “Technology can help a newly diagnosed family find answers faster and help a disease that affects so few families reach people around the world. It’s not just asking people to pay attention—it’s creating the tools that make it easier to understand, participate, and help.”

For End Alexander Disease day on April 7, Cancelleri and his wife made custom T-shirts for the entire staff at Levi’s school. Everyone wore them. During the morning announcements, the school did a segment on Alexander disease and fifth graders spread the word for students to give Levi a high-five when they saw him in the hallway.

“My purpose is to help raise awareness in any way that I can,” Cancelleri says. “If even five people learn about it, it’s five more people that didn’t know.”

If you want to learn more about Alexander disease, EndAXD provides information and resources for people and families affected by the condition, including updates on research and clinical trials. Visit endaxd.org to learn more.