FDA Approves Zanvastro, the First Treatment for Rare Alexander Disease

In the late 1990s, scientists at the University of Wisconsin-Madison bred mice that made too much of a brain protein called GFAP. The mice then did something nobody had planned. They developed the same telltale clumps found in the brains of people with Alexander disease, a rare and often fatal neurological disorder.³

“We had, really without intending to, created a mouse that produced these classic lesions of Alexander disease,” Albee Messing, a professor emeritus at UW-Madison, said in a university release.³

Science runs on careful planning and, every so often, on mice that go off script. This detour set off decades of work. On Sept. 3, 2026, the U.S. Food and Drug Administration approved Zanvastro (zilganersen), made by Ionis Pharmaceuticals, as the first treatment for Alexander disease. It is approved for both children and adults.¹

Alexander disease is estimated to affect roughly one in every 1 million to 3 million people worldwide.⁵ Until now, doctors could offer only supportive care and help with symptoms.⁴

Those mice led Messing and Michael Brenner of the University of Alabama at Birmingham to the cause: mutations in the GFAP gene. That discovery meant families could get a genetic blood test for diagnosis instead of a brain biopsy, which requires taking a tissue sample from the brain. A blood draw is a much easier ask.³

How the drug works (the name is the hard part)

In Alexander disease, the GFAP protein builds up in brain cells and causes damage. Zanvastro is an antisense oligonucleotide, a phrase that sounds like the final round of a spelling bee. In plain words, it is a short, lab-made strand of genetic material designed to cut down how much of the faulty protein cells produce before it can pile up.¹

The FDA says it is the first therapy to go straight after that protein buildup.¹ It is not a cure. The goal is to slow or steady the disease. Patients get a 50 mg dose injected into the spinal canal once every three months.⁸

The drug came out of Messing’s lab at UW-Madison’s School of Veterinary Medicine and Waisman Center, in partnership with Ionis.³

What the trial showed

The main study began in summer 2021. It enrolled 54 people, ages 1.5 to 53, at 13 sites in eight countries.³⁵ Most were children.

Two out of every three received Zanvastro, and the rest were in a comparison group. Neither patients nor doctors knew who got what during the 60-week treatment period. That secrecy is the point, since it keeps everyone’s hopes from nudging the results.⁷

In patients 5 and older, the drug met the study’s main goal. Their walking speed on a 10-meter walk test held steady at Week 61 compared with the comparison group, a result unlikely to be due to chance, though the margin was modest.²

Children ages 2 to 4 improved on a scale that measures big-muscle skills like sitting, crawling and walking. Side effects were mostly mild to moderate, and there were fewer serious problems than in the comparison group.⁶

The trial included very few infants. Even so, the FDA judged the evidence strong enough to cover patients from infancy through adulthood.⁴

“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.” (Emily Freilich, MD, FDA Division of Neurology I)⁴

A federal agency, ahead of schedule

The FDA moved quickly, which is not a sentence that gets typed every day. Zanvastro had Orphan Drug, Fast Track and Breakthrough Therapy status, and the approval came 19 days before the agency’s Sept. 22 deadline. By federal paperwork standards, that is a sprint.²

“Today’s approval represents a fundamental shift, changing the conversation from ‘How do we manage this disease’ to ‘How can we treat it,’” said Emily Petty, president of the patient group End Alexander Disease.²

“This is a wonderful and long-awaited day for the Alexander disease community,” Messing said.³

Ionis said the drug would reach U.S. patients in the weeks after approval. Outside the United States, access will come through a licensing deal between Ionis and the drug company Recordati.³ Not bad for a project that started with some mice going off script.