A novel adeno-associated virus (AAV) vector-based gene therapy designed to specifically express SMN protein in neurons led to better extended survival in a mouse model of spinal muscular atrophy (SMA) compared to onasemnogene abeparvovec (Zolgensma®), according to a new study presented at the American Society of Gene & Cell Therapy (ASGCT) 25th Annual Meeting.

Onasemnogene abeparvovec is a gene therapy that inserts a fully functional copy of the human SMN gene inside cells. It is approved in many countries across the globe to treat patients up to 2 years of age with all types of SMA.

Even though onasemnogene abeparvovec has already been used to treat more than 1000 patients with SMA with significant clinical benefits like the achievement of motor milestones and prolonged event-free survival, the treatment is accompanied by several challenges including insufficient expression levels and off-target effects. 

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Read more about onasemnogene abeparvovec for the treatment of SMA

The novel gene therapy reported here by Zhenhua Wu, PhD, and colleagues, called EXG001-307, is being developed by Exegenesis Bio. It is designed to achieve tissue-specific SMN production and reduce off-target toxicity.

“EXG001-307…has demonstrated a better extended survival, greater motor improvement and significantly reduced toxicity in a mouse model of SMA,” the researchers wrote.

The meeting took place from May 16, 2022, to 19, 2022 in Washington DC. The meeting abstracts were published in Molecular Therapy.

SMA is caused by biallelic mutations in the SMN1 gene, which normally encodes for most of the functional SMN protein in the body. In humans, there is a second gene encoding SMN protein called SMN2, but due to an alternative splicing event, most of the protein made from this gene is nonfunctional. SMN is essential for the survival of motor neurons. Thus, its deficiency leads to neurodegeneration, progressive muscle wasting, and loss of movement.


Wu Z, Zhu P, Wang Q, et al. A novel AAV-based gene therapy for spinal muscular atrophy. Poster presented at: American Society of Gene & Cell Therapy (ASGCT) 25th Annual Meeting; May 16-19, 2022; Washington DC.