FDA approves first drug for Alexander disease

Alexander disease is a rare genetic disorder that affects fewer than one in a million people. It can cause loss of movement, seizures and speech problems, and it is often fatal. The disease is caused by a fault in the gene that makes glial fibrillary acidic protein, or GFAP. Abnormal forms of that protein clump into tangles called Rosenthal fibers, which damage brain support cells called astrocytes, along with the brain's myelin.

The newly approved drug, zilganersen, is given by injection into the spinal canal. It works through small pieces of DNA called antisense oligonucleotides, which block production of the faulty GFAP protein. In a trial of 54 patients at 13 sites in eight countries, younger patients kept or improved their motor skills. Older patients held their walking speed steady, unlike those who received no treatment. Over more than a year, the drug also met all required safety standards.

Most side effects were mild or moderate. The most common were vomiting, back pain, cough, headache and pain after the spinal injection. Some patients developed aseptic meningitis, an inflammation of the lining around the brain and spinal cord. Serious side effects were less common in treated patients than in the control group.

Research leading to the drug began with mice bred to overproduce GFAP. The animals developed Rosenthal fibers, the classic lesions of Alexander disease, which pointed to GFAP as a target for therapy. The team later designed zilganersen to suppress GFAP production and tested it in animals before a human trial began in 2021.

The approval does not cure the disease, but it can slow its progression and improve symptoms by targeting the underlying cause. Albee Messing, a neuropathologist at the University of Wisconsin-Madison who has studied the condition for more than 30 years, called it "a wonderful and long-awaited day" for the Alexander disease community. The research team thanked patients and families for their support and participation.