WASHINGTON — The Food and Drug Administration has approved Zanvastro, the first therapy shown to alter the course of Alexander disease, an ultra-rare progressive disorder of the nervous system that until now had only symptomatic care.
The antisense oligonucleotide drug, developed by Ionis Pharmaceuticals, is injected into the spinal canal by a trained clinician every three months. Ionis said it will become available in the United States in the coming weeks; use abroad is expected through a licensing deal with Italy’s Recordati.
Alexander disease affects fewer than one in a million people worldwide. Mutations in the GFAP gene cause the protein to accumulate in astrocytes, forming Rosenthal fibers that damage myelin and disrupt motor, cognitive and autonomic functions. Symptoms can include seizures, loss of developmental skills, mobility problems and trouble eating or speaking. Onset can occur from infancy through adulthood.
Trial results
In a trial that began in 2021, Ionis evaluated Zanvastro in 54 patients at 13 sites worldwide. After a little more than a year of treatment, patients walked significantly faster than untreated peers, and motor function stabilized or improved in some cases, according to a University of Wisconsin–Madison summary of the approval. The FDA label covers patients from infancy through adulthood.
Zanvastro works by reducing production of GFAP before the protein can build up further. The approach grew out of more than 30 years of research led in part by Albee Messing at UW–Madison’s Waisman Center, who with collaborators created rodent models that unexpectedly reproduced hallmark Alexander disease lesions and later helped identify GFAP mutations as the cause.
“This is a wonderful and long-awaited day for the Alexander disease community,” Messing said in a university statement. He credited patient and family participation for making the research program possible.
From mouse models to medicine
Messing and Michael Brenner’s work in the 1990s linked GFAP overexpression to Rosenthal fibers and enabled blood-based genetic diagnosis instead of brain biopsy. Later collaboration with Ionis produced the ASO strategy that became Zanvastro after successful animal studies.
For families who previously faced only supportive therapies, the approval marks the first disease-modifying option for a condition that is often fatal. Clinicians and regulators are expected to continue monitoring long-term safety as the drug enters routine use. Because Alexander disease varies widely by age of onset, specialists say access to genetic testing and specialty neurology centers will remain important so eligible patients can be identified promptly for treatment.
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