GAN

J R Soc Interface  2017:20170123.

Giant axonal neuropathy-1 (GAN1) is an autosomal recessive neuromuscular disorder that affects both the central and peripheral nervous systems. There is no cure for GAN1 and only symptomatic treatments are available. The disorder leads to a progressive decline in mental function, loss of control of body movement, and seizures. It is caused by mutations in the GAN gene which encodes a protein called gigaxonin that plays an important role in the breakdown of neurofilaments. A phase I clinical trial using adeno-associated vectors (AAV) to rescue GAN gene expression was started in 2015 but its effects were unclear, as post-trial autopsies showed evidence of toxicity in the dorsal root ganglion (DRG) of patients who received intrathecally administered gene therapies. 

While a cure for GAN is currently unavailable, advances in molecular genetics have opened doors to gene and nucleic acid-based therapies. We explore the use of synthetic DNA-like molecules called antisense oligonucleotides (ASOs) for GAN treatment. We hypothesize that ASOs induce splice modulation, restore full-length GAN expression, and lead to morphological improvement in a patient-derived cell model of GAN. Our current project aims to evaluate the effects and safety of patient-customized n-of-1 ASOs.

Last updated: 1 October, 2023