First drug for a rare brain disease gets FDA approval
For people with Alexander disease, a rare and deadly neurological condition, a treatment now exists. The FDA approved Zanvastro after a trial in which treated patients maintained their walking ability while those in the control group declined significantly.
Alexander disease damages myelin, the protective sheath surrounding nerve fibres. Without this insulation, communication between neurons becomes increasingly impaired. The disease often begins in childhood and leads to progressive motor and cognitive deterioration. Until now, no disease-modifying therapy existed.
Zanvastro, developed by Ionis Pharmaceuticals, is an antisense oligonucleotide: a short strand of genetic material designed to block the production of a harmful protein in the brain. The researchers found in the pivotal trial that walking speed, a standard measure of motor function, remained stable in treated patients, while those in the control group saw a 33% decline. In young children, there were indications that the drug not only stabilised but may have improved motor function.
How antisense therapy works
Antisense oligonucleotides work by binding to specific RNA inside the cell, blocking the production of a target protein. In Alexander disease, mutations in the gene for the protein GFAP cause it to accumulate at toxic levels in astrocytes in the brain. By reducing GFAP production, the drug slows damage to brain tissue. Ionis has used this same platform for other neurological conditions.
For the longevity field, this approval is less directly relevant, but it demonstrates that targeted gene silencing in rare brain diseases can be both feasible and safe. These platforms may eventually be applied to more common neurodegenerative conditions.
Safety and limitations
Serious adverse events were more common in the control group than in treated patients, suggesting a favourable safety profile. The study was small in size, which is inevitable for a rare disease, and long-term effects have not yet been fully characterised.
Search terms to explore further: antisense oligonucleotide neurodegeneration, GFAP mutation myelin disease, RNA silencing brain disease therapy