The Transient Receptor Potential (TRP) calcium channels TRPC1 and TRPC3 could be novel therapeutic targets for Duchenne muscular dystrophy (DMD), according to a new study by researchers from France.
This idea is based on the fact that these 2 calcium channels seem to be involved in changes in sarcolemma permeability to calcium, which is an early and critical step in the pathogenesis of DMD.
In a series of experiments conducted in a rat model of DMD, the team of researchers led by Bodvaël Fraysse, PhD, showed that calcium homeostasis was altered in rats with DMD and that TRPC3 and TRPC1 protein levels were increased, as published in the Journal of Translational Medicine.
Moreover, the researchers showed that inhibiting TRPC3 eliminated the difference in sarcolemma permeability to calcium between wild-type and animals with DMD.
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Gene therapy with microdystrophin using a recombinant AAV vector (rAAV) led to the prevention of calcium homeostasis changes, skeletal muscle force, and TRPC3 increase, albeit partial.
“All together our results show that correcting TRPC3 channel expression and/or activity appears to be a promising approach as a single or as a rAAV-based complementary therapy to treat DMD,” the researchers concluded.
Now, more research is needed to further explore the effect of inhibiting TRPC3 channel expression and/or activity.
TRPC1 and TRPC3 are members of the mammalian TRP channel superfamily that encompasses 28 members. It is thought that they may be involved in the increase of the sarcolemma permeability to Ca2+ through the accumulation of Ca2+ permeable ion channels. An increase of the sarcolemma permeability to Ca2+ is known to lead to intracellular Ca2+ overload observed in DMD.
Creisméas A, Gazaille C, Bourdon A, et al. TRPC3, but not TRPC1, as a good therapeutic target for standalone or complementary treatment of DMD. J Transl Med. 2021;20;19(1):519. doi:10.1186/s12967-021-03191-9