Isis Pharmaceuticals develops a spinal muscular atrophy drug

Isis Pharmaceuticals announced that it has added a new drug to its development pipeline, ISIS-SMNRx, specifically designed to treat spinal muscular atrophy (SMA). Isis is developing ISIS-SMNRx as part of its strategy to discover and develop antisense drugs against neurodegenerative diseases. ISIS' SMA program is part of its collaboration in neurodegenerative disease with Genzyme, pursuant to which Genzyme has an exclusive option to license ISIS-SMNRx from ISIS.

SMA is caused by a genetic deletion of the survival motor neuron 1 (SMN1) gene. ISIS-SMNRx is designed to treat SMA by modulating the splicing of a closely related pre-mRNA (SMN2), which leads to the production of the protein, survival motor neuron (SMN), which is associated with normal motor function. By altering splicing to produce SMN, ISIS-SMNRx may be able to compensate for the underlying genetic defect. ISIS-SMNRx is the first antisense drug to enter Isis' development pipeline that modulates splicing, a novel antisense mechanism.

"With ISIS-SMNRx we have broadened the application of our technology beyond an RNase H based mechanism that inhibits the production of a disease-causing protein to an RNA splicing based mechanism that increases the production of a protein important for normal function", said Stanley T. Crooke, M.D., Ph.D., Chairman and Chief Executive Officer of Isis. "There are a large number of serious diseases that are associated with splicing disorders. The ability of antisense drugs to specifically target the RNA that drives splicing makes our antisense splicing drugs uniquely suited to correct aberrant splicing caused by genetic disease and to provide a therapy for these previously untreatable diseases. This significant advance expands the application of our drug discovery technology to help patients with these severe splicing disorders".

Splicing is a normal mechanism that the cell uses in order to produce many different, but closely related proteins from a single gene by varying the processing of the RNA. It is estimated that of the approximately 25,000 genes in the human genome, 40% to 60% have alternative splice forms. In some cases, alternative splicing of proteins results in the production of proteins that are involved in disease. These diseases are referred to as splicing diseases and include SMA, cystic fibrosis and Duchenne's muscular dystrophy.

Isis is exploiting its expertise in RNA to discover and develop novel drugs for its product pipeline and for its partners. The Company has successfully commercialized the world's first antisense drug and has 21 drugs in development. Isis' drug development programs are focused on treating cardiovascular, metabolic and severe neurodegenerative diseases and cancer.

(source: ISIS website)