Scientists have made a remarkable discovery about a woman who possesses unique qualities, including the inability to feel pain, accelerated healing, and reduced anxiety and fear. A team from the University College London has unraveled the distinctive molecular composition of this woman, named Jo Cameron, shedding light on a rare genetic mutation that accounts for her virtually pain-free existence.
The study, published in the journal Brain, builds upon the team’s previous identification of the ‘FAAH-OUT’ gene and the rare mutations responsible for Cameron’s lack of pain sensation and absence of anxiety and fear. The latest research outlines how the FAAH-OUT mutation suppresses the expression of the FAAH gene, subsequently affecting other molecular pathways associated with wound healing and mood. The findings hold promise for the development of new drug targets and the exploration of novel research avenues in these domains. Jo Cameron, residing in Scotland, was referred to pain geneticists at UCL in 2013 after displaying an absence of pain following major surgeries.
After an extensive six-year investigation, researchers identified a new gene, named ‘FAAH-OUT,’ harboring a rare genetic mutation. The combination of this mutation with another more common mutation in FAAH was determined to be the cause of Jo’s extraordinary characteristics. The study aimed to comprehend the molecular mechanisms underlying FAAH-OUT, representing the initial step towards leveraging this unique biology for applications such as drug discovery. This encompassed various approaches, including CRISPR-Cas9 experiments on cell lines to simulate the mutation’s impact on other genes, as well as gene expression analysis to identify active genes involved in pain, mood, and healing pathways.
The research team observed that FAAH-OUT regulates FAAH expression, and when the mutation carried by Cameron significantly reduces its activity, FAAH enzyme levels are correspondingly diminished. Additionally, two other crucial genes, BDNF (associated with mood regulation) and ACKR3 (involved in opioid regulation), exhibited alterations that may contribute to Jo Cameron’s reduced anxiety, fear, and pain. Professor James Cox from UCL Medicine emphasized that understanding the precise molecular mechanisms paves the way for insights into the underlying biology and the potential discovery of drugs that could greatly benefit patients.
