SMA

JCI Insight 2023; 8(5):e160516.

Spinal muscular atrophy (SMA) is a genetic disorder that is the leading cause of infant mortality, affecting 1 in 6,000 live births. It causes progressive muscle weakness and loss of motor neuron function, leading to loss of voluntary movement and death in early childhood. It is a multi-organ disorder affecting the heart, liver, thymus, muscles, and spleen.

Currently, there are three FDA-approved drugs for SMA: an antisense oligonucleotide nusinersen (brand name Spinraza), gene therapy Onasemnogene abeparvovec (brand name Zolgensma), and a small molecule Risdiplam (brand name Evrysdi). However, these treatments have drawbacks such as repeated intrathecal injections, off-target effects, toxicity, and limitations in age range. Our current study is examining the in vivo efficacy of an artificial DNA-like molecule called antisense oligonucleotide (AON) with delivery tools in a severe SMA mouse model. Our results show that systemic delivery of an AON with a delivery tool significantly improves the efficacy in reducing neuromuscular pathology, overall survival, and functioning.

Last updated: 7 June, 2023