Genetic Blood Disease Nearly 100% Cured With New Therapy
Gene therapies herald the future of
medicine, as they promise to do the impossible - cure hereditary
diseases that were either completely or mostly out of reach for previous
medical therapies. And now, for the first time, we have proof that gene
therapies, namely CRISPR, can permanently cure two hereditary blood
disorders - sickle cell anemia and beta-thalassemia.
CRISPR is a highly promising gene therapy that has the potential to be
used for a variety of hereditary health conditions. The cutting-edge
technology is capable of fixing genetic mutations by replacing them with
healthy bits of DNA. A blood condition named sickle cell anemia and
another related disorder called beta-thalassemia were among the first to
be successfully treated with CRISPR.
What are sickle cell anemia (SCA) and beta-thalassemia (TDT)?
Sickle cell anemia is a dreadful blood disorder that affects millions
worldwide and is considered one of the most common blood diseases in the
United States. SCA is a hereditary condition that disproportionately
impacts people of African-American heritage.
Sickle cell anemia is widely researched, which makes it a great
candidate for CRISPR. Scientists have isolated a single genetic mutation
that causes this condition. This mutation affects hemoglobin - a
compound in the red blood cell responsible for carrying oxygen to the
cells in the body. Beta-thalassemia is also caused by a few different
genetic mutations that alter hemoglobin.
The structure of hemoglobin in SCA patients
is atypical, which contorts the red blood cells out of their usual flat
and round shape into a sickle shape, so they’re more likely to stick
together and block blood vessels. For this reason, SCA patients have a
higher risk of stroke, and the deformed red blood cells can also clog
the liver, heart, spleen, lungs, or eyes.
As a result of both conditions, the altered hemoglobin isn’t able to
provide the body with enough oxygen, and patients suffer from chronic
fatigue, shortness of breath, and in the case of SCA, extremely painful
attacks called sickle cell crises.
Until recently, the only known cure for both of these conditions was a
bone marrow transplant - a risky and difficult procedure that isn’t
available for all patients. Patients also need frequent blood
transfusions, antibiotics, and pain relief medications to manage the
condition on a day-to-day basis.
CRISPR Gene Therapy
The treatment for these two blood disorders
was developed by CRISPR Therapeutics and Vertex. The first trials for
sickle cell disease and beta-thalassemia began in 2020, with a promising
outcome. But now, 3 years following the beginning of the trial, the
initial positive results still last for the majority of participants.
The therapy is called CTX001, or simply exa-cel, and it’s a single-dose
treatment that alters the patients’ cells to start making the kind of
hemoglobin they did at birth, which isn’t warped. The results of the
trial were presented at the European Hematology Association Congress,
and they reported the results of 75 participants. The gene therapy
trials were collected from the blood stem cells of participants.
Of these participants, 44 were TDT patients, and 42 were
transfusion-free following the treatment. The other two patients
required fewer transfusions. Of the SCD patients, all of them were free
of sickle cell attacks. Although two patients experienced initial
adverse effects, they resolved on their own over time. Moreover, the
effectiveness of exa-cel did not diminish even three years following the
treatment. So currently, the majority of participants are essentially
cured of the disease.
To sum up, a single-dose CRISPR treatment administered to patients with
sickle cell anemia and beta-thalassemia is showing a consistent and
lasting improvement in the patients’ well-being even 3 years following
the therapy. The researchers will continue monitoring the patients to
see whether or not these results are permanent. “Although we must
continue to investigate the durability of these results, I am excited
about the current data,” said the author of the trial abstract Stephan
A. Grupp of the Children’s Hospital of Philadelphia.