Glorioso expects it will be 18 to 24 months before an experimental therapy is ready to test in humans. When a patient feels pain they take the drug, which cuts the the power to the neurons’ electrical activity and shuts down the perception of pain, with minimal body-wide side effects and risks of addiction. A one-time injection into the skin sends the virus into the nerve cells, delivering the instructions for making this tunable on/off switch. The idea is to use a virus that evolved in nature to infiltrate the hyperexcitable nerves responsible for many kinds of neuropathic pain-from arthritic joints to thrown-out backs and nerve damage caused by many cancer treatments. Based in South San Francisco, Coda has so far raised $19 million to engineer receptors in people’s sensory neurons that can be controlled by a small molecule drug. In 2014, Glorioso cofounded Coda Biotherapeutics, to develop a gene therapy approach for treating chronic pain. “But we envisage a wide group of patients could potentially be helped.” “It’s early days so there’s lots to consider,” says Cox. So they’re also looking at a more permanent solution: editing DNA in cells directly to replicate Cameron’s pain-blocking microdeletion. But managing chronic pain would require frequent shots or infusions. That could potentially provide temporary, local relief. Some of them include designing and injecting a complementary RNA sequence that represses FAAH-OUT’s production. Because the mutation occurs in a pseudogene called FAAH-OUT-meaning a gene that makes a long string of RNA that doesn’t code for a protein but acts as a regulator elsewhere in the genome-they’ll have multiple options. That will help them figure out the best strategy for potential therapeutics. James Cox, a molecular geneticist at University College London who identified Cameron’s genetic anomaly says his group is now using Crispr in human cell lines to try to mimic her microdeletion and better understand its effects. She also doesn’t have an internal alarm system to alert her to broken bones, degenerated joints, and wounds.) (For Cameron, the Scottish patient, the downsides of her unique DNA so far only seem to include forgetfulness and never feeling this “adrenaline rush” she’s heard so much about. Trade-offs for other, less-well-studied genes, might be even more unpredictable. Great, right? But it also increases the likelihood of diabetes. Removing a gene called PCSK9, for example, significantly reduces one’s risk of a heart attack. Knock out a gene here or add code there and you might create other problems. “We don’t really understand how complicated biology is,” Crispr co-inventor Feng Zhang told 60 Minutes in a segment last spring. Namely, that DNA rarely acts in a straightforward fashion. What if you could genetically edit out not just pain, but existential dread and angst from the human condition altogether?Ī push toward permanently altering the genes of the next generation has so far been limited both by an intense ethical debate over whether humans have enough knowledge to direct the species’ own evolution and by practical challenges. And the advent of Crispr offers an even more tantalizing possibility. Pharmaceutical firms are currently deep into clinical trials on a drug that is able to mimic these effects. For decades, scientists have sought out rare families whose members exhibit similar pain insensitivity, and they have found in their DNA at least one other string of genetic code that functions as volume knob for human suffering. It is uncommon, but not unheard of, in human biology for a sensation as complex as pain to be controlled by a single gene. They published their findings Tuesday in the British Journal of Anaesthesia. Weirdly, any wounds she gets also heal faster than other people, and she cannot recall ever having felt anxious, depressed, or scared. After years of investigating, they identified the never-before-seen mutation believed to be responsible for her almost supernatural pain tolerance. Doctors discovered there was something different about Cameron when she came in for surgery and turned down painkillers after the nerve blocker from her operation wore off. As the 71-year-old Scottish woman recounted to The New York Times earlier this week, she has lived a life virtually free of pain, fear, and anxiety, thanks to a missing stretch of DNA. For Jo Cameron, it takes the sight of blood or the smell of her own flesh burning for her to know that something is very wrong.
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