The patient, Victoria Gray, age 41, from Mississippi, had the painfully debilitating disease since birth. Although Victoria was the first U.S. patient to have her cells altered, the first global patient received CRISPR treatment several months ago in Germany for a similar disease called beta thalassemia. One of the two biotech companies leading the study, CRISPR Therapeutics, reported that this patient has shown improvement and has not required blood transfusions for four months.
The sickle cell disease is caused by hemoglobin S, a faulty protein that alters the chemistry of red blood cells. The cells cave in and form a shape similar to a sickle. The deformed red blood cells are unable to transport the normal supply of oxygen usually provided by healthy cells.
Pain and fatigue will usually result when tissues and organs are deprived of oxygen.
Currently, the only treatment for the disease is a bone marrow transplant. The transplant, however, has only been successful in ten percent of patients.
CRISPR is an acronym for clustered, regularly interspaced, short palindromic repeats.
In sickle cell disease, the repeats refer to DNA sequences. When they are matched with the Cas9 enzyme these DNA-cutting scissors remove, replace and chop various DNA segments.
For Victoria’s CRISPR procedure, stem cells were extracted from her bone marrow.
CRISPR targeted BCL11A which represses a protein called fetal hemoglobin. Cells are normally protected by fetal hemoglobin and kept from being “sickled”. In effect CRISPR “tweaked “ the DNA causing it to activate fetal hemoglobin.
The edited cells were returned to Victoria’s bone marrow and should be at work returning her red blood cells back to normal. From this point on, Victoria and her doctors wait for an increase in the fetal hemoglobin and a corresponding decrease in the sickled cells.
Prior to returning the edited cells back into the bone marrow, doctors must first treat the unedited (original) stem cells with chemotherapy and radiation, thereby “damaging” the cells. These procedures prevent sickle cells from overtaking the healthy cells.
CRISPR is capable of cutting any type of DNA segment and for that reason, scientists must proceed with caution. There is the ever-present possibility of off-target cuts.
There are other types of risks such as the recent controversial case in China of the CRISPR editing of two human embryos. The woman who was the recipient of the embryos gave birth to twins in November 2018.
When CRISPR is used to edit an embryo, every cell in that “eventual” human body is altered. At this juncture, scientists do not know what adverse events may occur. Many scientists have called the editing of human embryos an ethical misstep and the procedure is illegal in certain countries.
Conversely, with regard to the treatments for sickle cell, only one type of stem cell is edited. It is limited to red blood cells and will not be passed along to future generations.
The Next Phase
Vertex Pharmaceuticals of Boston, Massachusetts in partnership with CRISPR Therapeutics, intends to enroll about 45 people 18 to 35 years of age in a joint study to determine CRISPR’s ability to genetically modify deformed sickle cells permanently.
Scientists agree that Victoria and the first global recipient (who thus far chooses to remain anonymous) must be observed for up to fifteen years before they can fully understand whether the fetal hemoglobin solution will be long-term and what, if any, unintentional effects occur as a result of CRISPR.
Although you may not be familiar with CRISPR, have you or anyone you know received a stem cell treatment or a transplant for any common disease or condition?