The U.S. Food and Drug Administration (FDA) has approved the first drug for the treatment of Alexander disease, a rare progressive neurological disorder that can cause severe impairments in motor and cognitive functions, as well as dysfunction of the autonomic nervous system, including control of heart rate and breathing, Medical Xpress reports.
The drug, Zanvastro, is the first and currently the only treatment capable of modifying the course of the disease, whereas previously treatment was limited to managing its symptoms.
Alexander disease is an ultra-rare disorder, affecting fewer than one person per million worldwide. Its first symptoms may appear in infancy, childhood, or adulthood. Possible symptoms include seizures, loss of previously acquired skills, impaired mobility, difficulties with eating and speech, and increased intracranial pressure.
Zanvastro directly targets GFAP, a protein that plays a key role in the development of the disease. The drug reduces production of this protein, preventing it from accumulating in brain cells and causing further damage. The medication is administered into the spinal canal once every three months by a healthcare professional.
The development of the drug was the result of more than 30 years of research that began at the University of Wisconsin–Madison. Professor of comparative biosciences Albee Messing, now an emeritus professor and former director of the Waisman Center, played a key role in the work. The research was conducted in collaboration with scientists from other institutions and with the participation of Ionis Pharmaceuticals.
In the late 1990s, Messing and his colleague Michael Brenner discovered the genetic cause of Alexander disease. The researchers created genetically modified mice that produced elevated levels of GFAP. Unexpectedly, the animals began developing characteristic accumulations of the protein in astrocytes, cells of the nervous system.
These accumulations, known as Rosenthal fibers, are one of the characteristic features of Alexander disease. Subsequent genetic analysis of patients confirmed that the disease is associated with mutations in the GFAP gene. This enabled scientists to identify the protein itself as a potential therapeutic target.
Using improved models of the disease, Messing and his colleagues began searching for a way to reduce GFAP levels. In collaboration with Ionis Pharmaceuticals, they developed antisense oligonucleotides—short strands of nucleic acids capable of suppressing the production of a specific protein. Positive results in animal experiments allowed the researchers to proceed to clinical trials, which began in the summer of 2021.
A study conducted by Ionis Pharmaceuticals involved 54 patients at 13 medical centers around the world. Patients who received Zanvastro for just over a year had significantly higher walking speeds than participants who did not receive the treatment. Overall, the drug helped stabilize motor function, and some patients even experienced improvements.
The FDA approved Zanvastro for patients of all ages, from infants to adults. The drug is expected to become available in the United States within the next few weeks. In other countries, its distribution will be carried out under a licensing agreement between Ionis Pharmaceuticals and the Italian pharmaceutical company Recordati.
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