Several drug candidates for giant axon neuropathy

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An initial French study, supported by the AFM and using zebrafish models of giant axon neuropathy (GAN), has identified new drug candidates:

  • Using pharmacological screening to identify small molecules that can restore both physiological and cellular deficits in the animal model.
  • High-resolution behavioural, computational and imaging analyses enabled the researchers to select five drug candidates.
  • These molecules restore locomotion and axonal growth and stabilise neuromuscular junctions in the zebrafish model.
  • They could be integrated into a repositioning approach to accelerate the development of a treatment for this neuropathy.

A Canadian team has developed a new mouse model of NAG :

  • These mouse models were developed by inactivating gigaxonin and overexpressing peripherin, two cytoskeletal proteins.
  • At 12 months, they develop cognitive disorders as well as major sensory and motor deficits.
  • In vitro administration of Tubastatin A (an HDAC6 inhibitor) to the neurons of these mice restored the level of axonal transport of microtubules to its normal level.
  • Treatment of the mice with this molecule slightly improved motor function.

 

A multilevel screening pipeline in zebrafish identifies therapeutic drugs for GAN. L. Lescouzères, C. Hassen-Khodja, A. Baudot et al. EMBO Mol Med . 2023 May 5;e16267

 

A New Mouse Model of Giant Axonal Neuropathy with Overt Phenotypes and Neurodegeneration Driven by Neurofilament Disorganization. B. Nath et JP. Julien. J Neurosci. 2023 May 31;43(22):4174-4189.

 

Axonal Transport Defect in Gigaxonin Deficiency Rescued by Tubastatin A. B. Nath, D. Phaneuf et JP. Julien. Neurotherapeutics. 2023 Jun 2

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