In a groundbreaking revelation, a group of scientists has made a remarkable discovery about an extraordinary woman who possesses an array of exceptional attributes. This woman, named Jo Cameron, exhibits an astonishing molecular composition that renders her incapable of experiencing pain, grants her accelerated healing abilities, and imbues her with reduced anxiety and fear.
The esteemed team from University College London embarked on a quest to unravel the biological mechanisms underlying Jo Cameron's extraordinary condition, which stems from a rare genetic mutation.
Building upon their previous breakthrough in 2019 regarding the 'FAAH-OUT' gene and its association with Cameron's virtually painless existence and absence of anxiety and fear, the researchers published a compelling study in the esteemed journal Brain.
The latest research sheds light on how the FAAH-OUT mutation orchestrates a downregulation of FAAH gene expression, consequently influencing various interconnected molecular pathways associated with wound healing and mood regulation.
These remarkable findings hold immense promise, as they could potentially pave the way for novel drug targets and spark new avenues of investigation in these intriguing domains.
Jo Cameron, a resident of Scotland, first came under the scrutiny of pain geneticists at UCL in 2013, after her physician astutely noted her complete absence of pain following major surgical procedures on her hip and hand. After six years of tireless exploration, the researchers successfully identified a previously unknown gene, which they aptly named 'FAAH-OUT,' harboring a rare genetic mutation.
Dr. Andrei Okorokov, a senior author of the study from UCL Medicine, elucidated, "The 'FAAH-OUT' gene represents merely a minute fragment of an expansive continent, which this study has begun to map. In addition to unraveling the molecular basis of her pain insensitivity, these investigations have revealed molecular pathways implicated in wound healing and mood regulation, all influenced by the 'FAAH-OUT' mutation."
When combined with another more commonplace mutation in FAAH, this newfound genetic variant was found to underpin Jo's extraordinary attributes.
The UCL team embarked on an endeavor to comprehensively comprehend the workings of 'FAAH-OUT' at a molecular level, constituting the crucial first step toward harnessing this unique biology for potential applications in drug discovery. Their multifaceted approach encompassed diverse methodologies, including CRISPR-Cas9 experiments on cell lines to simulate the mutation's impact on other genes, as well as gene expression analyses to ascertain the activation of specific genes implicated in pain, mood, and healing.
Significant downregulation of FAAH enzyme activity
The team observed that FAAH-OUT modulates the expression of FAAH, whereby a significant downregulation of FAAH enzyme activity occurs due to the mutation carried by Jo Cameron.
"By gaining a precise understanding of the underlying molecular processes, we can delve into the intricate biology at play, opening up possibilities for drug discovery that could ultimately yield far-reaching benefits for patients," expressed Professor James Cox from UCL Medicine, underscoring the significance of these findings.
Two pivotal genes, BDNF, previously associated with mood regulation, and ACKR3, involved in opioid level regulation, exhibited alterations that might contribute to Jo Cameron's remarkable lack of anxiety, fear, and pain.