Genetic diseases such as Sickle Cell Anemia and others have posed
a serious and seemingly intractable problem for the science of medicine since
any cure would require the repair of the damaged gene(s) involved. However a number of significant technological
breakthroughs in recent years have begun to change that bleak impasse. In 2003, the complete mapping of the human
genome was accomplished. This technology
and the information provided with its use have led to discoveries that have
pinpointed the genetic origin of many diseases and continues to do so. In 2012 a new tool was fashioned – the genomic
editor referred to as CRISPR. This
remarkable tool can precisely edit particular sequences within the introns of
targeted genes. The designers of this
capability, Jennifer Doudna and Emmanuelle Charpentier were awarded the Nobel
Prize in Chemistry in 2020. These two
advances are changing the prospects for the treatment of genetic diseases. CRISPR and an additional methodology
(described below) have demonstrated great promise.
It has recently been reported in the prestigious scientific
journal Science that, “Two strategies for directly fixing malfunctioning
blood cells have dramatically improved the health of a handful of people with
these genetic diseases. One relies on
CRISPR, marking the first inherited disease clearly helped by the powerful tool
created just 8 years ago. And both treatments are among a wave of genetic
strategies poised to expand who can get durable relief from the blood
disorders. The only current cure, a bone marrow transplant, is risky, and
matched donors are often scarce.”
The two genetic diseases referred to are so-called, “blood
disorders.” One is Sickle Cell Anemia,
and the other is Beta Thalassemia. Sickle
Cell Anemia is a disease in which the red blood cells are mishappen and their ability
to carry oxygen to the tissues is seriously compromised. The origin of this disease is genetic -the
alteration of both alleles that carry the blueprint for hemoglobin protein, the
protein responsible for binding oxygen.
This disease particularly impacts the African-American population. In Beta Thalassemia, the patient makes little
or no functional hemoglobin. The result,
for the patient, is a dangerous and debilitating anemia since the body’s tissue
cannot receive enough oxygen to effectively function.
The treatment devised that has been applied to both Sickle
Cell Anemia and Beta Thalassemia involve modifying the genes that carry the information
for the structure of hemoglobin in the following way. The stem cells responsible for producing red
blood cells resident in the bone marrow are harvested from the patient, and the
BCL11A gene responsible for shutting off the fetal form of hemoglobin is
disabled thereby allowing it to be produced.
The research tool utilized for this kind of genetic modification is
CRISPR. The patient then receives
chemotherapy to destroy any resident diseased cells and the modified stem cells
are then reintroduced into the patient.
If successful, the patient will then produce red blood cells with the completely
functional fetal hemoglobin.
In addition, Dr. David Williams from Boston Children’s
Hospital has achieved the same result using a novel technique - a specially genetically
engineered virus is utilized to introduce a fragment of DNA encoded RNA into
the harvested stem cells that effectively silences the BCL11A gene (referred to
It has been reported that, “Patients treated in both trials
have begun to make sufficiently high levels of fetal hemoglobin and no longer
have sickle cell crises or, except in one case, a need for transfusions.” The Boston team described a particular case in
of a teenager, “who can now swim without pain, and a young man who once needed
transfusions but has gone without them for nearly 2.5 years.”
These are, indeed, exciting developments, but represent only the beginnings of what could be an amazing era in the approach to many other diseases of this kind.