Gene Therapy Biotech AveXis Targets SOD1 ALS

A delivery for ALS? AveXis is currently using the gene therapy vector NAV AAV9, developed by REGENXBIO in Maryland, to deliver its experimental gene therapy for SMA into the spinal cord. The approach, which aims to increase levels of SMN, is beginning to show signs of benefit including motor function according to interim phase 1 results presented by Nationwide Children’s Hospital’s Jerry Mendell and colleagues at the 2017 meeting of the American Academy of Neurology in Boston. [Image: National Human Genome Research Institute.]

AveXis is one step closer to developing a potential gene therapy for SOD1 ALS. The gene therapy company, based in Cleveland, Ohio, announced this month it has obtained the rights to develop treatments for ALS using REGENXBIO’s gene therapy delivery vehicle. The emerging vector, derived from adeno-associated virus 9 (AAV9), is being increasingly utilized to deliver potential therapies into the CNS for neurological diseases.

The strategy is one of a growing number of potential gene therapies for SOD1 ALS that aims to reduce levels of misfolded SOD1 in the CNS and in the muscles by silencing the expression of the SOD1 gene (see May 2017 conference news). The approach is being developed by a research team led by Nationwide Children’s Hospital’s Brian Kaspar in Ohio, who is also AveXis’ chief scientific officer and scientific founder (see December 2015 conference news; Thomsen et al., 2014; Foust et al., 2013).

The delivery vehicle, known as NAV AAV9, forms the basis of AveXis’ experimental gene therapy for the motor neuron disease spinal muscular atrophy (SMA). The strategy, known as AVXS-101, is currently being evaluated at the phase 1 stage at Nationwide Children’s Hospital as a treatment for Type 1 SMA, the most severe form of the disease. The approach builds on previous studies in 2009 led by Institute of Myology’s Martine Barkats in France and Brian Kaspar in the United States, which found that AAV9 could cross the blood-brain barrier and therefore, could be used to potentially treat motor neuron diseases (see December 2008 news; Duque et al., 2009Foust et al., 2009).

Meanwhile, Martine Barkats, in collaboration with Maria Grazia Biferi, in France is using a different approach in hopes to treat SOD1 ALS (see May 2017 conference news). The strategy, which uses a related gene therapy delivery vehicle known as AAV10, also aims to reduce motor neuron toxicity by silencing the expression of the SOD1 gene. The strategy is currently being optimized and is at the preclinical stage. The researchers are now developing a similar strategy in hopes to treat C9orf72 ALS, the most common form of the disease.


To learn more about gene therapy and its potential for ALS, check out our recent news feature: A New Potential Gene Therapy Delivers A Key Milestone.


Thomsen GM, Gowing G, Latter J, Chen M, Vit JP, Staggenborg K, Avalos P, Alkaslasi M, Ferraiuolo L, Likhite S, Kaspar BK, Svendsen CN. Delayed disease onset and extended survival in the SOD1G93A rat model of amyotrophic lateral sclerosis after suppression of mutant SOD1 in the motor cortex. Neurosci. 2014 Nov 19;34(47):15587-600. [PubMed].

Foust KD, Salazar DL, Likhite S, Ferraiuolo L, Ditsworth D, Ilieva H, Meyer K, Schmelzer L, Braun L, Cleveland DW, Kaspar BK. Therapeutic AAV9-mediated suppression of mutant SOD1 slows disease progression and extends survival in models of inherited ALS. Mol Ther. 2013 Dec;21(12):2148-59. [PubMed].

Duque S, Joussemet B, Riviere C, Marais T, Dubreil L, Douar AM, Fyfe J, Moullier P, Colle MA, Barkats M. Intravenous administration of self-complementary AAV9 enables transgene delivery to adult motor neurons. Mol Ther. 2009 Jul;17(7):1187-96. [PubMed].

Foust KD, Nurre E, Montgomery CL, Hernandez A, Chan CM, Kaspar BK. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol. 2009 Jan;27(1):59-65 [PubMed].

Further Reading

van Zundert B, Brown RH Jr. Silencing strategies for therapy of SOD1-mediated ALS. Neurosci Lett. 2017 Jan 1;636:32-39. [PubMed].

Tora MS, Keifer OP Jr, Lamanna JJ, Boulis NM. The challenges of developing a gene therapy for amyotrophic lateral sclerosis. Expert Rev Neurother. 2017 Apr;17(4):323-325. [PubMed].

AAN2017 aav9 c9orf72 disease-als gene therapy SOD1 vector
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