For the first time, the use of gene editing has allowed the life of a one-year-old girl affected by an aggressive form of leukaemia to be saved. And this seems to be just the beginning
Lyla was born healthy on 10 June 2014. But just after three months, she was diagnosed with Infant Acute Lymphoblastic Leukaemia (ALL); “one of the most aggressive forms of the disease we have ever seen” said one of the doctors at Great Ormond Street Hospital (GOSH) in London, where she was sent right after the diagnosis. The baby girl was treated with rounds of chemotherapy and a bone marrow transplant, but nothing seemed to work. In June 2015, instead of going through palliative care, Lyla’s parents together with doctors decided to try an experimental form of gene therapy that had only previously been tested on mice.
Waseem Qasim, professor of cell and gene therapy at University College London’s (UCL) Institute of Child Health and a consultant immunologist at GOSH, was developing a gene therapy treatment for cancer based on cells known as UCART19. Using a technique called TALENs that works as accurate molecular scissors (which I talked about here as well), Qasim engineered immune cells called T-cells from a healthy donor in order to reach two goals. Firstly, cells are reprogrammed to target leukaemia cells specifically and, secondly, another gene is disabled in order to make them invisible to a leukaemia drug that would rather kill them.
Lyla was treated with 1ml of UCART19 cells delivered via intravenous injection and, within a few weeks, the treatment gave better results than any possible prediction. Today, after five moths, Lyla is in remission, that means that there are no more cancer cells detectable in her blood and she’s alive and healthy. “The only way we will find out if this is a cure is by waiting that one or two years, but even having got this far from where we were is a major, major step” said Dr Paul Veys from GOSH.
This is the second time that gene-edited cells have been used for experimental treatments on people, but the first time on a patient in immediate life danger. In the other case, a company based in California, Sangamo BioSciences, treated 12 HIV patients using gene-edited T-cells and published the result last year. As explained on Nature, using a different DNA-cutting enzyme called a zinc-finger nuclease (ZFN), they inactivated the expression of a protein known for being an HIV preferential target and, afterwards, re-injected the cells into the patients. As a result, half of the patients managed to stop taking their drugs and other patients are currently under treatment.
The third major gene-editing enzyme class is perhaps the most famous one: CRISPR/Cas9. Doudna and Charpentier’s incredible technique already hit the news earlier this year when it was used to experimentally edit the DNA of an embryo for the first time in China.
These new techniques are allowing researchers to do things that were impossible only a few years ago. In my opinion, Lyla’s case is a great example of how powerful and game changing these new methods can be. I think that we have only just scratched the surface of their possibilities, and that further and wider studies must be conducted before these gene-editing approaches can be safely and regularly use for patients’ treatment.
As Qasim told the BBC: “The technology is moving very fast, the ability to target very specific regions of the genome has suddenly become much more efficient. The technology itself has got enormous potential to correct other conditions where cells are engineered and given back to patients or to provide new properties to cells that allow them to be used in a way we can only imagine at the moment.”
Header image: CRISPR-mediated gene editing. Stephen Dixon and Feng Zhang, McGovern Institute.