Ionis Pharmaceuticals has developed an antisense drug (IONIS-DMPKRx) for the potential treatment of DM1. DM1 is caused by an abnormal expansion of three nucleotide repeats within the DMPK gene. The severity and age of onset of DM1 correlates with the number of triplet repeats, which increases from one generation to the next.


The genetic defect in the DMPK gene creates a toxic RNA rather than a disease-causing protein. The toxic RNA accumulates within the nucleus of the cell and prevents the production of proteins essential for normal cellular function. IONIS-DMPKRx is designed to target the toxic RNA and reduce its accumulation, thereby restoring normal cellular function. In animal studies, Ionis Pharmaceuticals showed that an antisense compound targeting the DMPK RNA entered muscle cells and significantly reduced the toxic RNA.

Effective reductions of toxic RNA led to a reversal of the disease symptoms, mainly myotonia, that was sustained for up to one year after treatment in a mouse model of DM1. Hence by removing toxic RNA, IONIS-DMPKRx was studied as a potentially effective approach to treating patients with DM1. 

Phase I Trial Summary

Ionis Pharmaceuticals has completed a Phase I study evaluating the safety of IONIS-DMPKRx in healthy volunteers. In this study, IONIS-DMPKRx was well tolerated at all dose levels tested with no safety or tolerability concerns. The compound was delivered by a subcutaneous injection. All study participants completed the study.

A Phase I/IIa study to evaluate the safety and dose-range finding of IONIS-DMPKRx in patients with DM1 has completed. 

Phase I/II Trial Summary

Results from the Phase I/II Trial study were announced on January 5, 2017: Ionis Pharmaceuticals Reports DMPKRx Phase 1/2 Trial Results. Ionis Pharmaceuticals and Biogen also released a letter to the DM community in January 2017.

Click here to see the Ionis Pharmaceuticals drug development pipleline. 


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