A French team is developing an effective preclinical approach in CMT 1A by combining siRNA and squalene nanoparticles

Type 1A Charcot-Marie-Tooth disease is the most common form of CMT. It is due to a duplication of the PMP22 gene causing overexpression of the PMP22 protein which accumulates in Schwann cells, which disrupts the myelin sheath and slows the transmission of nerve impulses. 

French researchers have developed a new approach with a small interfering RNA (siRNA) targeting PMP22 associated with squalene nanoparticles, a natural lipid used in drugs and cosmetics. This combination helps reduce the degradation of interfering RNA and better target the peripheral nervous system. Injected in 5 intravenous doses distributed over a period of 20 days to two mouse models suffering from CMT 1A (moderate and severe form), the product allows for three weeks to: 

  • decrease the amount of PMP22, 
  • restore the myelin sheath,
  • restore electrophysiological parameters and motor skills to a normal level.


Squalenoyl siRNA PMP22 nanoparticles are effective in treating mouse models of Charcot-Marie-Tooth disease type 1 A. Suzan Boutary, Marie Caillaud, Mévidette El Madani, Jean-Michel Vallat, Julien Loisel-Duwattez, Alice Rouyer, Laurence Richard, Céline Gracia, Giorgia Urbinati, Didier Desmaële, Andoni Echaniz-Laguna, David Adams, Patrick Couvreur, Michael Schumacher, Charbel Massaad & Liliane Massaad-Massade. Commun Biol 4, 317 (mars 2021).