After 30 years, scientists finally have a drug for a deadly brain disease
The FDA has approved the first drug that directly targets Alexander disease, a devastating neurological disorder affecting fewer than one in a million people. Developed through decades of research, Zanvastro showed promising results in clinical trials, stabilizing motor function and even improving movement in some patients.
Key points
- The FDA has approved Zanvastro, the first drug designed to directly treat Alexander disease.
- The treatment emerged from over 30 years of research at the University of Wisconsin-Madison and a collaboration with Ionis Pharmaceuticals.
- In a 54-patient international trial, treated patients showed significantly better walking speeds and stabilized motor function.
The FDA has approved Zanvastro, the first drug designed to directly treat Alexander disease, an extremely rare neurological disorder that progressively damages the nervous system and can be fatal. The treatment targets an underlying biological process rather than only relieving symptoms.
The drug resulted from more than three decades of research at the University of Wisconsin-Madison's School of Veterinary Medicine and Waisman Center, led in part by Albee Messing, professor emeritus of comparative biosciences and former director of the Waisman Center. Ionis Pharmaceuticals collaborated on development.
About Alexander disease
Alexander disease affects fewer than one in every million people worldwide. Symptoms can include seizures, loss of developmental abilities, difficulty walking or moving, and problems speaking or swallowing. Some patients develop dangerously high pressure inside the brain.
The disease does not follow a single predictable course. Symptoms may first appear during infancy, childhood, or adulthood, with severity and progression varying by age of onset. For decades, doctors could only offer supportive care and symptom relief.
This is a wonderful and long-awaited day for the Alexander disease community
— Albee Messing
Discovery and clinical results
In the late 1990s, Messing and Michael Brenner, professor emeritus of neurobiology at the University of Alabama at Birmingham, identified the genetic changes responsible for Alexander disease. Their work began with an unexpected finding in genetically engineered mice that developed abnormal protein deposits called Rosenthal fibers, a defining characteristic of the disorder. Further studies confirmed that mutations in the gene for glial fibrillary acidic protein (GFAP) were the cause.
Messing then worked with Tracy Hagemann, an associate research professor at the Waisman Center, to create improved rodent models. With Ionis Pharmaceuticals, they pursued antisense oligonucleotides (ASOs) to reduce GFAP production. Zanvastro uses this strategy and is given by injection into the spinal canal once every three months.
An international trial conducted by Ionis across 13 sites enrolled 54 patients. After receiving Zanvastro for a little more than a year, treated patients had significantly better walking speeds than untreated patients. Results also indicated stabilized motor function, and some participants improved. The FDA approval covers people from infancy through adulthood. Zanvastro is expected in the U.S. within weeks, and outside the U.S. access will be handled through a licensing agreement between Ionis and Recordati.
