Novel peripherally‐restricted cannabinoids to treat impaired neuromuscular synaptic transmission in myasthenia gravis and other neurological disorders

  • Phillips, William D. (Chief Investigator)
  • McGregor, Iain S. (Chief Investigator)
  • Arnold, Jonathan (Chief Investigator)
  • Bowen, Michael T. (Chief Investigator)
  • Banister, Samuel (Chief Investigator)
  • Reddel, Stephen W. (Chief Investigator)
  • Odierna, Lorenzo (Chief Investigator)
  • Morsch, Marco (Chief Investigator)

Project: Research

Description

The goal of this proposal is to develop a peripherally restricted cannabinoid drug that can enhance neuromuscular transmission and restore muscle strength in myasthenia gravis and related disorders. The scientific rationale for this is based upon our recent finding that synthetic and endogenous cannabinoids (WIN 55,212 and anandamide) enhanced neuromuscular synaptic transmission in mice. A suitable peripherally restricted cannabinoid might then offer a new
therapeutic option for treating defects of NMJ signalling in neuromuscular diseases without unwanted psychoactive effects. Our data so far indicate that cannabinoids enhance transmission via a novel mechanism: by increasing the amount of neurotransmitter packed into each synaptic‐ vesicle; by altering the quantum. This new way to pharmacologically modulate synaptic transmission may have important implications for diseases where neuromuscular transmission is impaired (see below). Our work also suggests that cannabinoid(s) are produced endogenously by the muscle during exercise to mediate a, hitherto undiscovered, positive feedback mechanism that can increase synaptic efficacy at the NMJ during sustained muscle use.
Short titleCannabinoids
StatusActive
Effective start/end date20/11/1831/12/22