The patients will be infused with their own modified HSCs, with the goal of producing increased amounts of fetal hemoglobin to compensate for the decrease in functional
adult hemoglobin levels.
Mutations affecting
adult hemoglobin production are among the most common of all genetic variations, with about five percent of the world's population carrying a defective gene.
Understanding the fetal-to-adult hemoglobin switching is believed to have a clinical relevance of developing novel approaches of reversal of fetal hemoglobin production from
adult hemoglobin in patients [87].
Normal
adult hemoglobin is Hemoglobin A, consisting of two alpha chains and two beta chains.
Since fetal hemoglobin is more apt to ferric state compared to
adult hemoglobin (Hb A2), newborn infants have a greater tendency to methemoglobinemia.
In the article the researchers said they are one step closer to developing a feasible cure or long-term treatment options for patients with SCD, which is caused by a single DNA letter change in the gene for
adult hemoglobin, the principle protein in red blood cells needed to carry oxygen.
Example 2: Fetal hemoglobin is replaced by
adult hemoglobin (1) during the first 6 months of life.
In the fetus and newborn, however, fetal hemoglobin permits greater delivery of oxygen to tissues than
adult hemoglobin does.
There are approximately 300 hemoglobin molecules in each red blood cell, and each hemoglobin can carry four oxygens--one oxygen attached to each of two alpha chains, and two beta chains in the
adult hemoglobin. Therefore, each red blood cell can carry approximately 1,200 oxygen molecules, and each red blood cell must also have 1,200 iron molecules for oxygen attachment.
HbA makes up approximately 97% of normal
adult hemoglobin. For this reason, any mutation that affects the [alpha] or [beta]-chains, resulting in either a functional (qualitative/hemoglobin variant) or concentration (quantitative/thalassemia) change in HbA, has a dramatic affect on hemoglobin function in the adult.
Two of the four peptides of the fetal and
adult hemoglobin chains are identical, that is, the alpha ([alpha]) chains.
Fetal hemoglobin changes to
adult hemoglobin later in childhood.
The hemoglobin of juveniles (disc diameter 0.48 to 0.8 ram) has a higher affinity ([P.sub.50] = 2.3 mmHg in cellulo and 4.0 mmHg in tube feet of intact animals, pH 8.0 at 20[degrees]C) for oxygen than the
adult hemoglobin ([P.sub.50] = 11.4 mmHg, disc diameter 5 to 12 ram) (see Table 1).
There are two types of normal hemoglobin: fetal hemoglobin (HbF) and
adult hemoglobin (HbA).
However, people with sickle cell anemia and beta-thalassemia have genetic defects in their
adult hemoglobin gene.
