FDA approves first drug to target Alexander disease directly
US regulators have cleared zilganersen, the first treatment aimed at the root cause of a rare and often fatal brain disorder, after more than 30 years of research.
America’s Food and Drug Administration has approved the first medicine that tackles the underlying cause of Alexander disease, a rare genetic disorder of the brain. The drug is called zilganersen and will be sold under the name Zanvastro.
Alexander disease affects fewer than one person in a million around the world. It can bring seizures, trouble with speech and a loss of mobility, and it is often fatal. Until now, doctors could only manage the symptoms.
The condition begins with a fault in the gene responsible for a protein called GFAP. The faulty protein clumps into tangles known as Rosenthal fibres, which put strain on astrocytes, the brain’s helper cells. Those cells and the brain’s myelin are then damaged.
Zilganersen turns down the body’s output of GFAP. It does so using antisense oligonucleotides, short strands of DNA that suppress production of the protein. Treatment means a spinal injection from a healthcare professional every three months, and the approval applies to patients of any age.
Part of the evidence came from a trial of 54 children and adults, the oldest aged 53, at 13 sites in eight countries. Younger participants held steady or improved in their motor skills. Among older ones, walking speed stayed level, whereas it fell in people who went without the drug.
Safety checks over treatment lasting more than a year satisfied the regulator. Side effects were mostly mild or moderate, and serious ones turned up less often in the treated group than in the comparison group. Reported problems included sickness, a cough, aches in the back and head, and soreness after the injection. The FDA also flags a risk of aseptic meningitis, which is swelling of the membranes around the brain and spinal cord.
It has been a long road. Neuropathologist Albee Messing, of the University of Wisconsin-Madison, has studied the disease for over three decades. With colleagues including Michael Brenner of the University of Alabama at Birmingham, he began with mice bred to produce too much GFAP, and the animals unexpectedly developed the classic signs of the disease. That pointed to the protein as the obvious target.
After first checking whether existing approved drugs might help, the team designed its own. It was tested in animals before human trials began in 2021. One mother says her daughter’s personality is coming through more and more since starting treatment, and Messing credits the patient and family community for making the research possible.
Why it matters
Zanvastro is not a cure and does not reverse the disease. Even so, it can slow progression and ease symptoms by going after the cause rather than the consequences, which is rather good news for families who until now have had no treatment to turn to. It also stands as a reminder of how patient research carried out over decades can eventually pay off.
