Q & A by Dr. Waxman
TEA Member: Why should I donate to TEA’s Research Fund if I do not have inherited EM? How will research into inherited EM lead to drugs that relieve my pain?
Dr. Waxman: We are learning, from the mutations in people with inherited erythromelalgia (IEM), about the role of Nav1.7 in pain, and about how various parts of the Nav1.7 channel produce pain. These lessons are VERY valuable since they teach us the critical players in producing pain. In the aggregate, they have provided a basis for pharmaceutical companies to develop drugs that block Nav1.7.
BUT… Nav1.7 does not just produce pain in people with IEM who have mutations. There is good evidence that Nav1.7 is a key player in pain sensation in EVERYBODY, including people with non-inherited erythromelalgia (NIEM) who have normal Nav1.7 (no mutation). In this regard, I have enclosed three papers:
We have shown, and others have confirmed, that after nerve injury, the injured nerves produce too much Nav1.7. This is a major contributor to pain after nerve injury. This occurs in everybody, and does not require a mutation. See Black et al, 2008 in which we studied normal people (no mutation) who developed severe pain after nerve injury. We expect that, when Nav1.7 blockers are available, they will be helpful for these patients.
We also now understand that, even with no mutation, Nav1.7 is responsible for burning-type pain after burn injury, and for burning pain in response to inflammation (e.g. a bee sting). See Shields et al, 2012. Again, we expect Nav1.7 blockers, when available, to be helpful for all people with burning pain.
About 30% of normal people (no mutation) carry a variant of Nav1.7 that makes them more sensitive to pain. See Estacion et al, 2009.
More from Dr. Waxman: Much of this work is scientifically propelled by what we learn in people with EM due to mutations of Nav1.7. When the first clinical trials of Nav1.7 blockers take place, the pharmaceutical companies will probably want to focus on people with mutations in Nav1.7. But we believe that these Nav1.7 blockers should alleviate burning pain in general. Thus, I would predict that these drugs, when available, should help all people with EM, with and without Nav1.7 mutations, primary and secondary EM.
There is an analogy from lipid-lowering drugs (statin drugs, like Lipitor). These help everybody with high lipids. But their discovery was propelled by rare families in which mutations caused lipids to be unusually high. The situation is similar in EM. The mutations are pointing the way, but ultimately, the lessons that we learn will help ALL people with burning pain.
Finally, let me assure TEA and its members, that Dr. Joost Drenth and I are both interested in developing new treatments for EM. The fact that, 8 years after discovery of the first Nav1.7 mutations, pharmaceutical companies are moving closer to new drugs, is remarkable. The gene for Huntington’s disease was discovered in 1985, and still no good candidate drugs. In contrast, my hope is that, in the not too distant future, we will be moving into humans for clinical trials.