Neurological Sciences

, Volume 40, Issue 4, pp 661–669 | Cite as

Genetic neuromuscular disorders: living the era of a therapeutic revolution. Part 1: peripheral neuropathies

  • Giuseppe VitaEmail author
  • Gian Luca Vita
  • Claudia Stancanelli
  • Luca Gentile
  • Massimo Russo
  • Anna Mazzeo
Review Article


Recent advances in pathophysiological and genetic mechanisms of some neuromuscular diseases and a rapid progress in new pharmacological technologies led to an accelerated development of innovative treatments, generating an unexpected therapeutic revolution. In part 1, we report already commercially available drugs, just approved drugs and new therapeutic promises in the treatment of peripheral neuropathies. Hereditary transthyretin amyloidosis (hATTR) is a devastating disease due to amyloid accumulation in peripheral nerves, heart and autonomic system. The first specific drug approved for hATTR was tafamidis, a TTR tetramer stabilizer. In 2018, the positive results of two phase 3 trials have been reported leading to start of regulatory approval route for inotersen, an antisense oligonucleotide and patisiran, the first-ever RNA interference (RNAi) therapeutic. System biology targeting approach has indicated baclofen, naltrexone and sorbitol in combination (PXT3003) as candidate drugs for Charcot–Marie–Tooth disease type 1A. This hypothesis was confirmed in experimental models and in phase 2 and 3 clinical trials. Givosiran, another RNAi therapeutic, targeting 5-aminolevulinic acid synthase, has been positively tested in acute intermittent porphyria in phase 1/2 and ongoing phase 3 trials. Although allogenic hematopoietic stem cell transplantation resulted recently a long-term therapy in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a new strategy is liver transplantation which is able to revert the severe biochemical and clinical imbalance of the disease. Recently, a gene therapy has been tested in a MNGIE murine model, indicating that it may become a new therapeutic option.


Hereditary transthyretin amyloidosis Inotersen Patisiran Charcot–Marie–Tooth disease Acute intermittent porphyria Mitochondrial neurogastrointestinal encephalomyopathy 


Compliance with ethical standards

Conflict of interest

G.V. discloses having been on advisory board for Alnylam Therap., Akcea Therap, and Pfizer. He is also principal investigator in clinical trials sponsored by Alnylam Therap and Ionis Therap.


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Copyright information

© Fondazione Società Italiana di Neurologia 2019

Authors and Affiliations

  1. 1.Unit of Neurology and Neuromuscular Diseases, Department of Clinical and Experimental MedicineUniversity of MessinaMessinaItaly
  2. 2.Nemo Sud Clinical Centre for Neuromuscular DisordersMessinaItaly

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