FAAH-OUT! A new pain insensitivity gene

FAAH-OUT! A new pain insensitivity gene (Dr. James Cox, Nociception Lab, WIBR, UCL)

Millions of people worldwide are living in chronic pain. This pain is often poorly treated and the over-prescription of opioid-based drugs has contributed to an opioid epidemic that is causing significant morbidity and mortality. New pain-killing and non-opioid based medications are hence urgently needed. A powerful way to identify novel human-validated analgesic drug targets is to study rare individuals with intact damage-sensing neurons that present with a congenital pain insensitive phenotype. Here I will describe a new pain insensitivity disorder in which a female patient carries both a hypomorphic SNP in the fatty-acid amide hydrolase (FAAH) gene and a microdeletion downstream of FAAH in a novel gene called FAAH-OUT. This patient, in addition to being pain insensitive, also presents with additional clinical symptoms including a happy, non-anxious disposition, enhanced wound healing, reduced stress and fear symptoms and mild memory deficits. I will describe recent gene editing and CRISPR interference experiments that reveal the importance of the FAAH-OUT genomic region to normal FAAH expression. Our results highlight the potential of gene therapy targeting FAAH/FAAH-OUT for the development of novel non-opioid based analgesics.