Diagnosis of sicklecell anemia

 Diagnosis of sicklecell anemia:-

1. Sickling test : This is a simple microscopic examination of blood smear

prepared by adding reducing agents such as sodium dithionite. Sickled

erythrocytes can be detected under the microscope.

2. Electrophoresis : When subjected to electrophoresis in alkaline medium (pH

8.6), sicklecell hemoglobin (HbS) moves slowly towards anode (positive

electrode) than does adult hemoglobin (HbA). The slow mobility of HbS is

due to less negative charge, caused by the absence of glutamate residues that

carry negative charge. In case of sicklecell trait, the fast moving HbA and

slow moving HbS are observed. The electrophoresis of hemoglobin obtained

from lysed erythrocytes can be routinely used for the diagnosis of sicklecell

anemia and sicklecell trait.

FIG. - Electrophoresis of hemoglobins at pH 8.6 (HbA–Normal adult

hemoglobin; HbS–Sickle cell hemoglobin). 

Sicklecell trait provides resistance to malaria

Sicklecell trait provides resistance to malaria:-

The incidence of sicklecell disease coincides with the high incidence of malaria

in tropical areas of the world (particularly among the black Africans).

Sicklecell trait (heterozygous state with about 40% HbS) provides resistance

to malaria which is a major cause of death in tropical areas. This is explained as

follows

1. Malaria is a parasitic disease caused by Plasmodium falciparum in Africa. The

malarial parasite spends a part of its life cycle in erythrocytes. Increased lysis

of sickled cells (shorter life span of erythrocytes) interrupts the parasite cycle.

2. More recent studies indicate that malarial parasite increases the acidity of

erythrocytes (pH down by 0.4). The lowered pH increases the sickling of

erythrocytes to about 40% from the normally occurring 2%. Therefore, the

entry of malarial parasite promotes sickling leading to lysis of erythrocytes.

Furthermore, the concentration of K+ is low in sickled cells which is

unfavourable for the parasite to survive.

Sicklecell trait appears to be an adaptation for the survival of the individuals

in malaria-infested regions. Unfortunately, homozygous individuals, the

patients of sicklecell anemia (much less frequent than the trait), cannot live

beyond 20 years.

The future of gene therapy

 The future of gene therapy:-

Theoretically, gene therapy is the permanent solution for genetic diseases. But

it is not as simple as it appears since gene therapy has several inbuilt

complexicities. Gene therapy broadly involves isolation of a specific gene,

making its copies, inserting them into target tissue cells to make the desired

protein. The story does not end here. It is absolutely essential to ensure that the

gene is harmless to the patient and it is appropriately expressed (too much or too

little will be no good). Another concern in gene therapy is the body's immune

system which reacts to the foreign proteins produced by the new genes.

The public, in general, have exaggerated expectations on gene therapy. The

researchers, at least for the present, are unable to satisfy them. As per the

records, by 1999 about 1000 Americans had undergone clinical trails involving

various gene therapies. Unfortunately, the gene therapists are unable to

categorically claim that gene therapy has permanently cured any one of these

patients! Some people in the media (leading news papers and magazines) have

openly questioned whether it is worth to continue research on gene therapy!!

It may be true that as of now, gene therapy due to several limitations, has notprogressed the way it should, despite intensive research. But a breakthrough

may come anytime, and of course, this is only possible with persistent research.

And a day may come (it might take some years) when almost every disease will

have a gene therapy, as one of the treatment modalities. And gene therapy will

revolutionize the practice of medicine!

Gene replacement therapy

Gene replacement therapy:-

A gene named p53 codes for a protein with a molecular weight of 53 kilodaltons

(hence p53). p53 is considered to be a tumor-suppressor gene, since the protein it

encodes binds with DNA and inhibits replication. The tumor cells of several

tissues (breast, brain, lung, skin, bladder, colon, bone) were found to have

altered genes of p53 (mutated p53), synthesizing different proteins from the

original. These altered proteins cannot inhibit DNA replication. It is believed

that the damaged p53 gene may be a causative factor in tumor development.

Some workers have tried to replace the damaged p53 gene by a normal gene by

employing adenovirus vector systems. There are some encouraging results in the

patients with liver cancer.

The antisense therapy for cancer is discussed as a part of antigene and

antisense therapy