The woman cured with gene editing: ‘My supercells have changed my life’

More than four years ago, American Victoria Gray received a life-changing phone call. It was her hematologist, offering her entry into a clinical trial with an experimental drug. Gray, 37, has sickle cell anemia, the most common genetic disease in the world. About 300,000 babies are born each year with the condition, which is caused by a mutation that causes red blood cells to be crescent-shaped instead of round. These sharp blood cells get stuck in the vessels and cause crippling pain throughout the body, chronic damage to many organs and a high risk of dying from a stroke. Gray was given seven years to live at birth.

During gestation, the gene that dominates the production of hemoglobin, the protein that carries oxygen through the blood, works perfectly. But after birth, that gene shuts down and another one that will produce hemoglobin for the rest of life begins to function; and it is that one which has the mutation that causes the disease.

In July 2019, Gray became the first patient to receive a new therapy for her disease based on gene editing with CRISPR. This revolutionary technology invented in 2012 makes it possible to correct errors in the instruction book of 3 billion letters of DNA that make up the genome of a human being.

The new treatment involved extracting blood stem cells from Gray’s bone marrow, isolating them in the lab and using CRISPR’s molecular scissors to cut her genome right at the position of the BCL11A gene. This is the switch that turns off fetal hemoglobin production after birth. Automatically, the cells repaired the cut in the genome by rejoining their ends, but the gene had been disabled.

At this point came the hardest part: killing all the diseased blood cells in the patient’s bone marrow with chemotherapy. The doctors then transfused the woman with her own edited cells. Within weeks, a new generation of red blood cells loaded with healthy fetal hemoglobin nested and multiplied throughout her body.

Nearly four years later, Gray feels like she has a new life ahead of her. “I’m no longer in pain and haven’t had to be admitted to the hospital, when I used to have to go every few months.” For the first time she sees herself able to care for her four children without help and look for a full-time job.

This week Gray came to explain her case at the 3rd International Human Genome Editing Congress in London. Hundreds of experts in the field rose from their seats and gave her a standing ovation after her moving speech. “Thanks to my supercells,” she explained, her voice almost breaking, “my life has changed completely. It is the closest thing to a cure that has been seen since the disease was discovered 113 years ago.

Dozens of people in several countries have participated in clinical trials with this therapy, developed by Vertex Pharmaceuticals and CRISPR Therapeutics. And several similar ones are on the way against sickle cell anemia and beta-thalassemia, another genetically-based blood disorder that condemns people to life-long transfusions. These drugs are expected to be approved in the United States later this year and to reach Europe some time later.

Very expensive medications

These treatments will be among the most expensive in the world. They will cost around three million dollars (about 2.8 million euros), to which one must add the cost of several months of hospitalization, transfusions and chemotherapy. It is highly doubtful that such a product will reach the areas where more than 90% of sickle-cell anemia cases occur: Africa and India, with at least six million sickle-cell patients in total - although other estimates put the number at more than 20 million.

For many generations, penution has favored these to be the most affected areas because the anemia mutation has an advantage: it reduces the risk of malaria. Up to 80% of children with sickle cell anemia in sub-Saharan Africa die within a few years of life. And on the entire African continent, only three countries have the infrastructure to implement these new therapies: Nigeria, Tanzania and South Africa.

It is also difficult to see how these treatments will reach many patients in developed countries, especially those where there is no universal healthcare. Gray, for example, fears for her future grandchildren, who could inherit the disease. “I would hope that these expensive therapies can be made more affordable to help people like me. Otherwise, what’s the point of having developed them?” he explains.

The black population in the United States, descendants of African slaves, is the one that suffers the most from this anemia, with some 100,000 affected. In Latin America, there are 85,000, and in Europe, some 40,000.

Stanford University physician and researcher Mathew Porteus was one of the first to demonstrate that gene editing corrects enough blood cells to cure sickle cell patients. “This product has been tested in the United States and has worked there, but it will probably have to be simplified, industrialized and the form of administration changed if we want to bring it to other parts of the world,” he acknowledges. His great hope is India, a country where the cost of other therapies that are very expensive in developed countries has been drastically reduced. “India has all the technology to bring the price down,” he explains.

But Gautam Gondre, president of the sickle cell patient associations in India, is highly skeptical. Over the past 40 years, hydroxyurea has been shown to be the most effective treatment for relieving the symptoms of sickle cell disease. The monthly cost of this medicine is about 30 euros. “If in my country my two children cannot have access to this drug, how will they have access to CRISPR therapy?” cried Gondre during his speech.

Alexis Thompson of the Children’s Hospital of Philadelphia explained that gene-editing therapies for hematological ailments are not without risk and have a serious side effect: infertility. Data show that the younger patients are, the better they seem to respond to treatment. But chemotherapy often leaves them infertile.

Dan Bauer of Boston Children’s Hospital, another pioneer of these therapies, believes that more follow-up is needed before claiming to have cured the disease. The researcher explained that the available data show that there is a 45% correction of the blood cells and that this is enough for the crises and pain characteristic of the disease to subside. But until when? No one knows.

The future of gene editing

At the moment, these therapies work well with genetic blood diseases, which allow stem cells to be extracted, edited in the laboratory and checked to see if the defect has been corrected before injecting them into the patient. This is not possible when the disease affects a solid organ. This is one of the big goals for gene editing in the future because it would make it much cheaper. Attempts to cure a genetic liver disease with a direct injection of CRISPR have shown promising results against a rare disease of genetic origin. The goal for the next few years is to treat organs such as the heart and brain or to reduce bad cholesterol levels.

In addition, there are at least two new, much more versatile and precise gene-editing technologies that go beyond simple DNA cutting with CRISPR. Both have been developed by the laboratory of David Liu of Harvard University, who also participated in the conference. Base editing, which is already being tested in patients, makes it possible to replace one letter of DNA in the genome with another, correcting mutations. Prime editing, which is being tested in animals, makes it possible to correct longer sequences without introducing additional errors.

During his speech, Liu was optimistic about these new technologies. “After more than 70 years of scientific work, editing our genome is one of the most important capabilities that our species has achieved and can allow us to stop being condemned by the errors in our genome”.

Sign up for our weekly newsletter to get more English-language news coverage from EL PAÍS USA Edition