Blocking A Channel to Drug Overdoses?
It was reported just last week that the number of deaths from opioid overdoses has set a new record. The CDC reported Thursday that drug overdoses killed more than 70,000 Americans in 2017.1,2 Significantly, the sharp increase in these types of deaths, combined with a fifty year increase in suicides3, contributed to the third straight year that life expectancy in the United States has decreased. This has not happened since World War II. Since 1990, deaths from drug overdoses have increased by more than 650 percent, driven by opioids.4
These bleak statistics, along with the devastating damage opioids have inflicted even beyond the deceased, have spurred research into new pain management solutions that this class of drugs was originally meant to address.
As alternatives to opioids, ion-channel blocking peptides are a possible candidate for pain management. The natural world is full of venomous creatures with potential drug candidates, for treating conditions such as diabetes, pain, and cancer. Ziconotide, for instance, or ω-conotoxin MVIIA, was first isolated from the cone snail and can be used to treat chronic pain. Recently, a group, led by Bin Wu of Amgen, looked at channel blocking peptides derived from tarantula venom as a possible treatment for pain. The peptides ProTx-I, ProTx-II, HwTx-IV, Pn3a, GpTx-1, and JzTx-V are all derived from tarantula venom. Their work led them to a JzTx-V analog, with 80% homology to the native sequence, that “robustly” inhibited the Nav1.7 voltage-gated sodium channel. The Nav1.7 ion channel holds a critical role in pain signaling and is a good target for inhibition. Unfortunately, it was discovered that it requires high concentrations of the peptide analog to impact the Nav1.7 ion channel.5 Regardless, further research on modified peptide toxins targeting the Nav1.7 and other ion channels still holds promise for potential pain treatments.
5. B. Wu et al., J. Med. Chem., 61, 9500 (2018).