This might come as good news for many sufferers of Sickle Cell Anemia as
researchers have made what could be a stunning breakthrough to finding a
cure.
Scientists at the haematology division at The Children’s Hospital
of Philadelphia may have discovered a breakthrough in treating sickle
cell anaemia. Speaking at the American Society of Haematology’s (ASH)
annual meeting, the researchers put forward a new technique that hopes
to reverse the effects of the condition.
Sickle cell anaemia is a genetically inherited blood condition
where the recessive gene, typically hidden by its dominant equivalent in
the parents, reappears in their offspring, in what is known as an
autosomal recessive pattern of inheritance. Should a parent have the
condition, the likeliness of their child developing it is 50%. Should
both parents only have the recessive gene, the likelihood decreases to
one in four. The mutation responsible occurs on the gene responsible for
coding the beta-globin chain in haemoglobin, the compound that makes
blood cells red and carries oxygen to respiring tissue, replacing one
protein by another.
This seemingly innocuous swap means that the normally round and
flexible red blood cell becomes rigid and sickle shaped. As a result
they can become obstructed in the tiny capillaries within tissue, and
carry less oxygen around the body. However, scientists have found a way
of restoring fully functional red blood cells that could be used to
treat the condition if they are able to transfer their laboratory cell
culture findings to actual human tissue.
The technique is called “forced chromatin looping”
according Dr. Jeremy Rupon, haematologist at the Children’s Hospital of
Philadelphia, during a press conference on their novel findings.
This procedure causes the production of foetal haemoglobin, a type
of haemoglobin that is usually silenced soon after birth in preference
of adult haemoglobin production. As foetal haemoglobin is unaffected by
sickle cell anaemia, the researchers hope to use this reversal of a
biological switch to restart foetal haemoglobin production, with the
hope of treating the condition in patients. These findings are based on
previous work by Dr. Gerd Blobel, who also worked on the current
project, published back in the June 2012 edition of the journal Cell.
They discovered that the creation of a chromatin loop between the
separated enhancer and promoter regions of the beta-globin gene leads to
gene transcription, the process where DNA code is “read” and a copy is created to be sent to specialized areas in the cell to be produced and hence expressed.
And, thanks to Dr. Blobel and his team’s previous work, they knew
how to cause the looping thanks to the molecule known as looping factor
Ldb1 attached to a zinc finger protein, the latter allowing attachment
at a specific site on the DNA strand.
Dr. Rupon and his team designed and genetically engineered a zinc
finger protein to attach and force a loop at the site in the DNA strand
responsible for producing foetal haemoglobin. The loop allows the
reactivation of the gene, causing expression of the genetic code.
The cell cultures showed that this technique was effective in “reversing”,
so to speak, the biological switch responsible for silencing foetal
haemoglobin production. In the mice model, the researchers found that
this zinc finger/Lbd1 compound was extremely effective in promoting
embryonic beta-globin production, with the forced looping resulting in
an 800-fold increase in transcription.
A similar result was found when they tested human adult red blood
cells. These results are highly promising, and Dr. Rupon hopes to
advance this research to clinical trials, with the hope of curing sickle
cell anaemia.
In addition, this may be the first of many conditions to be treated
in this manner, said Dr. Rupon, with a variety of haemoglobin
conditions that could be solved by reverting to foetal red blood cells.
