Yokota T, Takeda S, Lu QL, Partridge TA, Nakamura A, Hoffman EP. A renaissance for antisense oligonucleotide drugs in neurology: exon skipping breaks new ground. Arch Neurol. 2009 Jan;66(1):32-8.
http://www.ncbi.nlm.nih.gov/pubmed/19139297

Yokota et al. argue for a reassessment of pharmaceutical regulations in light of exon-skipping oligomers, especially for Duchenne muscular dystrophy (DMD). The current regulations require testing in animals that is inappropriate for human-targeted oligos. Testing exon-skipping oligos in healthy volunteers will produce DMD RNA in the volunteer’s cells. Costs of approval for individual sequences are very high, but multiple exon-skipping oligos may be needed in a cocktail to address a single patient’s mutation. Current regulations require that each sequence go through independent clinical trials. This crushing cost burden ensures that many patients for whom supplying a lifesaving drug is technically feasible will never be able to receive that treatment in countries where pharmaceuticals are strictly regulated; only oligo sequences that can treat larger patient populations will go through the expensive approval process.

Exon-skipping drugs for DMD are desperately needed. Regulatory decisions regarding exon-skipping oligos are life-or-death decisions. I hope that this new paper by Yokota et al. is carefully considered by pharmaceutical regulators worldwide. Here are the key questions; the answers embedded in the decisions of regulators will determine the lifespans of thousands, yearly (DMD affects about 1 in 3000 live male births), and the life quality of many more, both those living with DMD and their families.