The idea is that CRISPR could correct the genetic mutation responsible for sickle-cell so that patients’ bodies could make normal red blood cells, alleviating the pain and other severe symptoms associated with the disease.
Sickle-cell disease, which afflicts approximately 100,000 Americans with immense pain and shortened life-span, is caused by a single mutated nucleotide within the gene that codes for haemoglobin. Although its cause has been understood for more than a century, patients with sickle-cell have historically been underserved by both the pharmaceutical industry and the medical establishment.
However, as CRISPR is changing the face of medicine, it may also be changing this lived reality for people with sickle-cell disease, which is caused by a single mutation that is well-studied, making it an appealing candidate for correction with the gene-editing tool. Despite the lingering safety concerns about using CRISPR in people, some sickle-cell patients and their doctors are already embracing it.
Researchers have already tested the gene-editing tool on human sickle cells in the lab and are now working on getting the technique to clinical trials. Early results hint that sickle-cell could be among the first diseases that CRISPR essentially cures.
CRISPR works by cutting into a DNA sequence in a specific place and either deleting
a sequence or editing it. In the case of sickle-cell disease, the mutation that causes the illness is a single nucleotide: a T where an A should be within the HBB gene, which codes for hemoglobin. Red blood cells with healthy hemoglobin are the typical disc-shaped red cells seen microscopically, but the mutation causes unhealthy sickle-shaped cells that stick together. Eventually this causes a buildup of cells, blocked blood vessels, and lack of oxygen to different regions in the body along with pain, organ damage, and eventually premature death. This one mutated nucleotide is an easy fix for CRISPR, which can simply cut and edit that nucleotide.Although CRISPR clinical trials have yet to begin in the US, the National Institutes of Health (NIH) is launching a study at the end of August 2017 to explore the opinions people with sickle-cell have about CRISPR technology.
Scientists and others from all over the world have been meeting and talking about ensuring that people have equal access to CRISPR, although thus far the issue has not passed the discussion stage. CRISPR Therapeutics is one of a handful of gene-editing startups pursuing new treatments for sickle-cell. The company’s approach involves isolating stem cells from samples of patients’ blood.
Scientists intend to use CRISPR to activate a genetic switch that would raise the levels of a fetal form of hemoglobin in red blood cells, turning them healthy. This fetal hemoglobin effectively counteracts the effects of the sickle mutation. The modified cells would then be infused back into the patients.
They believe this is the safest approach as opposed to the one employing the injection of the gene-editing mechanism directly into the patient. “Our hope is that it’s one-time and curative for life,” says Samarth Kulkarni, president of CRISPR Therapeutics.
If a CRISPR cure for sickle-cell eventually reaches the market, one major question is who will have access to it. The drug costs one to two dollars per day, but even that is too expensive for many. The cost of CRISPR might put a cure out of reach for most of the world’s patients.
However, until CRISPR is available, sickle-cell patients will have to cope with other treatments. CRISPR represents the promise for a better, longer life. And that hope might not be far off, with both academic and commercial labs racing to develop CRISPR-based therapies.
