Rendered Cas9
Results from clinical trials released Tuesday indicate that two patients, one with beta thalassemia and one with sickle cell disease, have potentially been cured of their diseases. The two trials, which involved using Crispr to edit the genes of the patients in question, were jointly conducted by Vertex Pharmaceuticals and CRISPR Therapeutics.
“This is the first clinical evidence to demonstrate that Crispr/Cas9 can be used to cure or potentially cure serious genetic illnesses,” Jeffery Leiden, CEO of Vertex, told Forbes. “It's a remarkable scientific and medical milestone.”
Vertex Pharmaceuticals CEO Jeffery Leiden
Crispr/Cas9 is a gene-editing system popular for its ability to snip, repair or insert genes into DNA. The therapies tested in the clinical trials work by extracting bone marrow stem cells from the patients, editing these stem cells to fix the genetic mutations that cause the diseases, and then infusing the cells back into the patients. The patient’s body then takes over and is able to produce new, healthy cells. Engineering of the cells is done ex vivo (outside of the patient’s body). This allows the researchers to make sure the correct changes are made and there are no improper edits to the genome.
CTX001, the gene-editing therapy used in these trials, is “very surgical in how it makes the change,” says David Altshuler, Vertex’s chief scientific officer.
It has been nine months since the patient with beta thalassemia received the one-time-only treatment and over four months for the patient with sickle cell disease. In that time, both of their conditions have improved tremendously, Leiden says. The patient with beta thalassemia, who used to undergo more than 16 blood transfusions each year, hasn’t needed an infusion since the treatment. The patient with sickle cell disease experienced an average of seven excruciating health crises per year before the treatment, and since the treatment hasn’t experienced any.
Despite the fact that these results have only been seen in two patients, says Samarth Kulkarni, CEO of CRISPR Therapeutics, “the effect is so dramatic in these patients that we can’t help but think this brings a lot of promise.”
CRISPR Therapeutics CEO Sam Kulkarni
Both patients suffered side effects during the treatment, but doctors concluded they were caused by the bone marrow preparation, not the Crispr treatment itself. In order to infuse healthy stem cells, both patients had to undergo intensive chemotherapy to destroy their old bone marrow cells. This treatment, also common for bone cancer patients, can cause nausea, hair loss and organ damage.
Precision medicine is known for its hefty price tag, and this treatment is “the zenith of precision medicine,” Kulkarni says. Yet when asked about potential cost of the treatment, Kulkarni says that they are still focusing on clinical development and it is “too early to contemplate any sort of pricing discussions." Zolgensma, the first FDA approved gene-therapy medication, was priced at $2.1 million last May.
The applications of Crispr seem limitless, but the field has encountered several ethical controversies. Last year, Chinese scientist He Jiankui shocked the medical community by announcing that he had altered the genes of two human children. One of the main worries that researchers have about Crispr is that scientists might alter genes to be inherited, a practice called germline engineering. In a recent article on the anniversary of He’s revelation, Crispr pioneer Jennifer Doudna called for stricter regulations for using Crispr in heritable human genome editing.
But germline editing isn’t a concern in these trials, where only somatic, or non-reproductive cells, were altered. People are “much more concerned about intentional changes to a person’s DNA that could be passed down to their descendants,” says Henry Greely, a Stanford law professor and chairman of the California Advisory Committee on Human Stem Cell Research. When it comes to somatic cells, “they die with the person," he says.
In addition to following these initial patients for the next two years to see if their diseases reoccur, Leiden says they’re enrolling multiple patients with both diseases for the next phase of the clinical trial and will be starting treatments for those patients in the near future. While they don’t yet have a timeline on when the treatment will be commercially available, “we want to get this to patients as soon as possible,” he says.
