by The genetic secret of a 75-year-old woman who lives without ever feeling pain despite the words anxiety and fear being almost unknown to her has been revealed by researchers from University College London (UCL).
The new study published in the journal “Brain” is a continuation of a previous discovery by the same group made in 2019 and linked to the gene FAAH-OUT and some rare mutations of it. Mutations in this gene cause it Joe Cameron from Scotland, a retired teacher, never to feel pain, stress and fear. New findings from UCL researchers shed light on how its mutations FAAH-OUT they ‘turn off’ gene expression and simultaneously, in a ‘domino’ effect, affect other molecular pathways associated with wound healing and mood. It is hoped that the results will lead to new therapeutic targets and open new avenues of research in all of these areas.
The… Tired Jo Cameron
Ms Cameron was first referred to geneticists at UCL in 2013, aged 65, by her GP who noticed she had not felt a single pain following operations major problems in her hip and arm – the doctors wanted to give her painkillers but she insisted she didn’t need them. Until then, her difference had its advantages – for example, she gave birth twice without feeling any pain and emerged unscathed from a car accident – but also significant disadvantages: she suffered from osteoarthritis and did not didn’t realize, she had burned herself while cooking. without knowing.
The genetic cause
After six years of study and follow-up of the patient, the researchers identified a new gene which they named FAAH-OUT, carrier of a rare genetic mutation. This mutation combined with another more common mutation of the gene FAAH found to be the cause behind the unique characteristics of women.
The precious DNA – “garbage”
The region of the genome that contains the gene FAAH-OUT it was thought to belong to so-called junk DNA, which has long been thought to be non-functional because it does not contain genes coding for protein production. However, it turned out that this region regulates the expression of the gene FAAH which is part of the human body’s endocannabinoid system and is known to be involved in pain, mood and memory.
As part of the new study, researchers tried to understand how it works FAAH-OUT at the molecular level – a first step towards understanding Jo Cameron’s unique biology so that its ‘secrets’ can then be used in applications such as drug development.
Different experimental approaches
To achieve this, the scientists used many different approaches, such as experimenting with CRISPR-Cas9 “molecular scissors” in cell lines to mimic the effect of the mutation on other genes. They also analyzed gene expression to see which were active in molecular pathways involved in pain, mood and wound healing.
The research team discovered that the gene FAAH-OUT regulates gene expression FAH. When gene activity is severely reduced as a result of the mutation carried by Jo Cameron, activity levels of the FAAH enzyme are also greatly reduced.
The Molecular Basis of Nociception
As mentioned by Dr. Andrei Okorokov from UCL Medicine, lead author of the study “The FAAH-OUT gene is just a small ‘dot’ on a vast continent, which this study has only just begun to map. Our explorations have shown the molecular basis of the absence of pain sensation as well as the pathways molecules that affect wound healing and mood – all of which are affected by the FAAH-OUT mutation.I believe these findings will have a significant impact on areas of research such as depression, recovery from injury, and more Again.”
And other “key” genes
The researchers also examined fibroblasts taken from the patient to study the effect of the axon FAAH-OUT-FAAH in other molecular pathways. As they saw as the mutations Cameron carries silence the gene FAAH, there were still 797 genes that are activated and 348 that are silenced. These genes are in the WNT pathway, which is linked to wound healing – in fact, the increased activity of a gene in this pathway, the WNT16, has already been linked to bone regeneration.
Two other “key” genes that showed mutation were the BDNF which has been linked to mood regulation and ACKR3 which helps regulate opioid levels. These mutations likely contribute to Cameron showing minimal anxiety, fear and pain, the researchers noted.
Towards the development of drugs for many patients
According to the teacher James Cox from UCL Medicine, also lead author of the new study “The initial discovery of the genetic root of Jo Cameron’s unique phenotype was a moment of wonder, but it’s the new discoveries that make things so much more interesting. By understanding exactly what is happening at the molecular level, we can begin to learn the biology behind this woman’s phenotype, paving the way for the development of drugs that could one day have a major impact on the lives of many patients.”
