A recent study investigating a rare genetic mutation in a patient who “feels no pain” has suggested new routes to developing gene-therapy based analgesics for the treatment of chronic pain. Alongside the rise of neuromodulation techniques, new analgesics that target the genes responsible for the sensation of pain provide non-opioid pain relief, further assisting in the alleviation of the opioid crisis seen today.
When a 66-year old female patient requested no painkillers after undergoing surgery on her hand, her anaesthetist decided to look further into her medical history. Seeing that she had little need for pain relief, even after having suffered from broken limbs and childbirth, the patient was referred to geneticists at University College London (UCL) and Oxford University (both in the UK).
Now, speaking to NeuroNews, lead author of the study, James Cox (Wolfson Institute for Biomedical Research, UCL, London, UK) details exactly what the genetic mutation has revealed as well as how the findings of the study contribute to the treatment of chronic pain, and the next steps moving forward.
What exactly has this genetic mutation uncovered?
We have studied a female patient who carries both a change in the fatty-acid amide hydrolase (FAAH) gene that makes the enzyme less active and also a microdeletion downstream of FAAH, in a novel gene called FAAH-OUT. This patient, in addition to being pain insensitive, also presents with additional symptoms including a happy, non-anxious disposition, enhanced wound healing, reduced stress and fear symptoms and mild memory deficits. The genetic mutations highlight the importance of the endocannabinoid system to pain perception and in particular FAAH as an analgesic and anxiolytic drug target.
How may your findings contribute to the treatment of chronic pain?
Millions of people world-wide 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 painkilling and non-opioid based medications are urgently needed. We hope that these findings will lead to the development of new analgesics that target FAAH/FAAH-OUT and provide better non-opioid based pain relief for chronic pain patients.
Do the findings expand the opportunities for personalised therapy for chronic pain?
“Chronic pain” should be thought of as lots of different diseases—just like ‘cancer’ can be subdivided into, for example, bowel, liver, prostate, or pancreatic cancer. If we can stratify chronic pain patients correctly with in-depth phenotyping and molecular genetic analyses, we will be able to make headway in treating distinct patient populations with the most appropriate analgesic drugs.
If and when new FAAH-based analgesics come to the clinic, we can then determine which subgroups of chronic pain patients would benefit from those types of painkillers.
Since the story was broken, has anyone else who does not experience pain come forward?
Yes, we have been delighted with the response, with over 80 pain insensitive patients getting in contact.
What are the next steps in terms of research?
We are looking forward to working with the new patients and begin sequencing their DNA—some of these patients may have mutations in known pain genes whilst others may have mutations in completely new ones. We are also keen to understand how the FAAH-OUT gene functions and are currently carrying out gene editing experiments in human cells to learn more about how it regulates FAAH expression. We are also excited at the prospect of using gene therapy as an approach to treat chronic pain James Cox and have several ongoing studies in this area.
