After more than thirty years of academic research in the United States, a first basic treatment has just been approved for a pathology that most doctors will never hear about during their careers. This is the Alexander’s diseasean ultra-rare, progressive and often fatal neurological condition that affects fewer than 1 in 1 to 3 million people worldwide according to the Food and Drug Administration (FDA) and Ionis Pharmaceuticals.
The new drug, Zanvastro (zilganersen), was authorized on September 3, 2026 by the FDA for all ages, from infants to adults. According to Emily Freilich, head of neurology at the FDA, “For patients with Alexander disease and their families, there were no approved treatment options, only supportive care while the disease progressed. Today’s approval is a pivotal moment for this community as it provides the first therapy that addresses the underlying cause of this rare and serious disease“.
How Zanvastro works on Alexander’s illness
Zanvastro is an antisense oligonucleotide, a small DNA sequence that blocks the production of a specific protein. In Alexander disease, gene mutations
GFAP lead to an overproduction of this protein in the brain’s supporting cells,
astrocytes. The resulting toxic clumps ultimately damage the nervous system. Zanvastro reduces the production of GFAP before it accumulates, by directly targeting the messenger RNA that encodes it.
Concretely, the treatment is given by intrathecal injection, that is to say in the spinal canal, every three months at a dose of 50 mg, carried out in the hospital by a trained professional. The pivotal trial NCT04849741, conducted on 49 patients aged 2 and over in the FDA analysis and 54 participants in total according to Ionis, shows at 61 weeks significantly better walking speed in patients aged 5 and over treated with Zanvastro, with an average difference of 33.3% compared to the control group.
Thirty years of research at the University of Wisconsin–Madison
This green light from the FDA crowns the work begun in the early 1990s by veterinarian and neurobiologist Albee Messing at the Waisman Center at the University of Wisconsin–Madison. With Michael Brenner, in the late 1990s he identified GFAP mutations as the genetic cause of the disease. By creating mice that overproduced GFAP, his team saw characteristic clumps called Rosenthal fibers appear. “This offered an obvious and precise treatment strategy: the GFAP protein.“, explains Albee Messing.
Using these animal models, Messing and his colleague Tracy Hagemann collaborated with Ionis Pharmaceuticals to develop the antisense that became Zanvastro. The human clinical trial began in summer 2021 in 13 centers across 8 countries. For Messing, who speaks of a true translational research journey, “This is a wonderful and long-awaited day for the community affected by Alexander’s disease“.
What Zanvastro’s approval changes for families
Until now, treatment was limited to treating epileptic seizures, swallowing disorders or breathing difficulties, without influencing the overall outcome. With Zanvastro, data shows a stabilization of walking in those over 5 years old, and an improvement in gross motor skills in children aged 2 to 4 years old. In infants under 2 years of age, the FDA relied on pharmacokinetic data and the tolerance observed in four babies to extend the indication, while recalling the scarcity of direct data.
The most common adverse effects remain fatigue linked to lumbar puncture (post-puncture syndrome), vomiting, headache or back pain, and a risk of aseptic meningitis monitored by clinicians. Ionis announces availability in the United States in the coming weeks, accompanied by an “Ionis Every Step” support program to help families navigate between education, insurance and follow-up. Outside the United States, marketing will take place through a licensing agreement with the Italian laboratory Recordati, with regulatory files planned in Europe and Japan from 2027.