A baby in the US has made history as the first recipient of a personalised gene-editing treatment, a breakthrough made possible by US taxpayer-funded research, underscoring what could be lost with the recent gutting of federal research funding, reports the New York Times.
Diagnosed with CPS1 deficiency, a rare genetic disorder affecting one in 1.3 million babies, at just a week old, the prognosis did not look good for baby KJ. Around half of all babies with the disorder die in the first week of life and those that survive experience severe mental and developmental delays and would eventually require a liver transplant.
When his parents opted to try to keep him alive despite the overwhelming odds, one of his doctors at Children’s Hospital of Philadelphia reached out to Dr Kiran Musunuru, a gene-editing researcher at the University of Pennsylvania. Over the next six months, dozens of researchers worked around the clock to develop a gene therapy for KJ, knowing that he was at growing risk of severe brain damage or death.
Dr Fyodor Urnov at the University of Berkley, who verified there were no unexpected or deleterious gene edits elsewhere in the DNA, told the Times that “such speed to producing a clinic-grade CRISPR for a genetic disease has no precedent in our field. Not even close.”
Their work seems to have saved KJ. After three doses, he is showing significant improvement in health markers and meeting developmental milestones, although the disease is still present in a lessened form. This breakthrough will likely save and improve a great many more lives in the future, both those with extremely rare conditions like KJ and with more common genetic disorders, like sickle cell disease, cystic fibrosis, Huntington’s disease and muscular dystrophy.
CPS1 deficiency is the result of a single mutation, an error in the genome that makes the body unable to rid itself of ammonia, a byproduct of protein metabolism. When ammonia builds up in the blood, it can cross into the brain and any spikes in ammonia levels, common with illness and infections, can cause severe brain injury or death.
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To help KJ, researchers targeted the single mutated gene using base editing, which carries instructions commanding the cells to produce an enzyme that edits the gene as well as what the Times terms “a molecular GPS” (CRISPR) programmed to crawl along the DNA strand until it finds the exact DNA letter that needs to be changed. While tailored to KJ, it could be adapted to fix mutations in other places by simply reprogramming the CRISPR instructions, dramatically cutting the cost of treatment.
KJ received the first infusion in February this year, at six months old, sleeping through the entire two-hour process. Within two weeks, KJ was able to eat as much protein as a healthy baby but still needed his medication, indicating that the gene editor had corrected the problem in only a portion of the affected cells. He received a second dose 22 days later, just half the original dosage, and a third earlier this month.
While it’s still too soon to know if he can come off the medication completely, he needs much less and has “sailed through” a few viral illnesses that could have killed him before, Dr Rebecca Ahrens-Nicklas, the Children’s Hospital of Philadelphia doctor who first reached out about gene editing, told the Times.
Some might call KJ’s case a miracle, but for Urnov it’s really “a triumph for the American peoples’ investment in biomedical research.” Federal funds supported the basic research on bacterial immune systems and the discovery it led to, CRISPR. Federal investment in genome sequencing made it possible to identify KJ’s mutation and other investments led to an understanding of KJ’s disease, knowledge that kept him alive long enough to develop the gene editing breakthrough. Such funds supported the lab that invented the gene-editing method used to fix his mutation, as well as the researcher first contacted on the case, Musumuru.
As President Donald Trump pushes to cut billions from science funding, including medical research, KJ’s case serves as an important reminder of why investment in science is critical. For the more than 30 million Americans living with one of over 7,000 rare genetic diseases, government investment is a lifeline.
Most conditions are so rare that no company would be willing to spend the time or money developing a treatment. Yet by investing in each stage of the scientific process, the federal government is able to support medical advances that help millions of Americans like KJ and people around the world.
