By studying the Opposite Phenotype “absence of pain” and the severe phenotype of spontaneous severe pain through rare disease genetics, we can apply this knowledge to the development of novel analgesics. Knowing what genes are critically involved in human pain perception provides key entry points into the development of novel analgesic drugs.
For the Opposite Phenotype we used our Extreme Genetics discovery platform to identify individuals with a human analgesia syndrome called Congenital Indifference to Pain (CIP). CIP is characterized by the total absence of pain perception, including pain-free broken bones, tooth abscesses and even child birth. We discovered CIP patients have genetic mutations, resulting in deficiency of the protein Nav1.7, a voltage gated sodium channel. Based on this severe phenotype of absence of pain in humans, we predicted that the single-gene defect causing CIP could define an important novel human drug target for treating pain. We have developed a small molecule inhibitor to Nav1.7 called XEN402 that we are developing with Teva for pain.
We have also discovered that not all patients with CIP have deficiency of Nav1.7 and these families represent additional opportunities to identify targets that are essential for human pain perception.