A few years ago, Scottish woman Jo Cameron was found to be a medical marvel who felt next to no pain, fear or anxiety, and had faster wound healing, thanks to a specific gene mutation. Now, scientists have studied in more detail to figure out how this works, in the hopes of unlocking future drug targets.
Cameron’s borderline superpower was only discovered in her mid-60s, after she underwent two major surgical procedures and reported little to no pain afterwards. When doctors followed up with her personal history with pain, she reported never really feeling minor cuts and scrapes, and some burns she didn’t even notice until she smelled burning flesh. She hadn’t needed painkillers after previous surgeries either.
Cameron was referred to pain geneticists at Oxford and University College London, who identified two gene mutations as the root of her condition. One was in a gene called FAAH, which was previously known to control pain, mood and memory. The other was previously thought to be a non-functioning “junk” gene, but from this case was found to mediate the expression of FAAH. So they named it FAAH-OUT.
In the new study, the team investigated how FAAH-OUT works biologically. Among their methods they used CRISPR gene editing on cells to check how the mutation affected other genes, and examined fibroblasts taken from other patients to study how FAAH and FAAH-OUT affect other molecular pathways.
It turns out that FAAH isn’t the only gene being turned down with these mutations – 348 others were also being suppressed, while an astonishing 797 genes were being turned up. Among them were the WNT pathway, which is linked to wound healing; BDNF, which is associated with mood regulation; and ACKR3, which regulates opioid levels. Altogether, these may help explain Cameron’s insensitivity to pain, her apparent wound healing speed boost, and her generally lower levels of anxiety and fear.
It’s an intriguing case study, and along with others like the Marsili family, could help scientists identify new targets for medication to dampen pain or improve mental health symptoms.
“The FAAH-OUT gene is just one small corner of a vast continent, which this study has begun to map,” said Dr. Andrei Okorokov, senior author of the study. “As well as the molecular basis for painlessness, these explorations have identified molecular pathways affecting wound healing and mood, all influenced by the FAAH-OUT mutation. As scientists it is our duty to explore and I think these findings will have important implications for areas of research such as wound healing, depression and more.”
The research was published in the journal Brain.
Source: UCL
