Antisense Oligonucleotide Development for Treatment of Spinal Muscular Atrophy

The SMN2 gene contains sequences that regulate the level of inclusion of SMN exon7 in SMN mRNA, and some of these act in a negative manner. Antisense oligonucleotides to block the negative regulating protein binding to these sites can increase inclusion of SMN exon 7 and thus, the amount of SMN being produced.

The Need

Spinal muscular atrophy (SMA) is an inherited disease affecting the central nervous system, peripheral nervous system, and skeletal muscle. It is present primarily in infants and children but can also develop in adults. About 10,000 to 25,000 children and adults are living with the disease in the United States.

There is no cure for SMA, and treatment consists of managing the symptoms and preventing complications. Physical therapy, occupational therapy, and rehabilitation help to improve posture, prevent joint immobility, and slow muscle weakness and atrophy. Gene therapies have been FDA-approved, but they are costly and ineffective in many cases.

The Technology

T2012-011 and T2014-166 both treat SMA by targeting certain sites of the survival motor neuron 2 (SMN2) gene to increase full-length SMN protein levels (by disrupting the binding of proteins that inhibit the inclusion of SMN exon 7 into the mature mRNA). Both show promising preclinical in vivo efficacy in the delta7 SMA mouse model. T2012-011 is a composition comprising an ASO and a contrast agent (e.g. iohexol), enabling delivery to the entire nervous system, including both the CNS and PNS. T2014-166 is a morpholino based ASO treatment.

Commercial Applications

  • The inventions can be used for the treatment of SMA.


  • No marked toxicity in any dose given in animal trials
  • Compares well with other ASO treatments for SMA
  • Increased weight in animal trials
  • ASO can be administered both intracerebroventricularly and systemically, resulting in correction of SMN in tissues outside the nervous system


US Pat. No. 9,725,716; US Pat. No. 9,845,469

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