A 13-year old girl in the U.K. saw her cancer go into remission after becoming the first person in the world to receive a treatment that relies on a newer type of Crispr gene editing called base editing.
It’s a wonderful first application of the technology, which allows scientists to make precise, single-letter changes to DNA. And while it’s still very early days for base editing — the first tool was discovered just six years ago — it’s stunning to watch how quickly new inventions are moving from the lab into potential cures.
Alyssa, the patient in the U.K., was diagnosed last year with a form of blood cancer called T-cell acute lymphoblastic leukemia, or T-ALL. Kids with T-ALL typically respond well to chemotherapy, and those who don’t go on to get bone marrow transplants. Unfortunately, Alyssa’s cancer stubbornly resisted both and she was out of options when her family was informed about an experimental therapy developed by Waseem Qasim, a professor of cell and gene therapy at University College London.
Qasim used base editing to make multiple modifications to a donor’s T-cells so that they would seek out and destroy cancer cells. In May, Alyssa became the first to receive the drug as part of a small trial that will eventually enroll 10 patients. Her cancer has been undetectable ever since, though doctors at Great Ormond Street Hospital for Children in London, where she was treated, are closely monitoring her for any changes. Researchers from the hospital say two more children are being considered for the T-ALL therapy, with the next patient potentially receiving the treatment in January.
It’s a wonderful first application
of the technology, which allows
scientists to make precise,
single-letter changes to DNA
“This is a very impressive technological feat, with the best possible clinical outcome so far in the one patient treated so far,” says Bruce Levine, a professor specializing in cancer gene therapy at the Perelman School of Medicine at the University of Pennsylvania. The thrill here is that base editing makes it easier for researchers to make a cluster of small changes, potentially widening the therapeutic possibilities for cell therapies. And while base editors could always make a mistake — changing the wrong letter of the genetic code — the newer technology does not, like the earliest Crispr tools, cause double-stranded breaks in DNA. (Those breaks have the potential to rejoin in the wrong way, creating a permanently problematic edit — and more edits mean more potential for incorrect pasting.)
Unfortunately, base editing still has a ways to go before it will be widely accessible. And the side effects immediately following infusion of the drug, while manageable, are no joke. Moreover, the body’s T-cell response is wiped out for a period of weeks while the therapy does its cancer-killing job. Because that made Alyssa vulnerable to new viruses or reactivation of ones she’s already been exposed to, doctors gave her a bone marrow transplant a month after her treatment in order to reconstitute those needed immune cells.
While Qasim’s study represented a first, several biotech firms using base editing have also made swift progress in getting drugs into humans. But that road hasn’t been without speed bumps. This summer, the Food and Drug Administration put on hold a base-edited cell therapy for T-ALL being developed by Beam Therapeutics. Like the treatment Alyssa received, Beam’s therapy requires multiple edits and the FDA wanted more data on the potential for errors. The agency lifted the hold earlier this month.
The FDA also put the brakes on the U.S. arm of a trial from Verve Therapeutics, which is using Beam’s technology for a therapy intended to permanently lower cholesterol — an approach already being put into action in patients in New Zealand. Verve revealed this month that it will need to provide the FDA with a long list of data, including answering questions about is potency and whether the edits could be passed on to a patient’s children.
Alyssa is only one patient and it’s too soon to say the word “cure.” But it’s also worth celebrating the success. The teenager told reporters about the joy of being at home with her family for Christmas and maybe being a bridesmaid in her aunt’s wedding. That’s a laudable first feat for any technology.
Lisa Jarvis is a Bloomberg Opinion columnist covering biotech, health care and the pharmaceutical industry. Source: Bloomberg
