Sickle cell disease/anemia treatment

Favorable results of exchange transfusion in a variety of diseases in adults, for example sickle cell disease, severe clotting disorders, hepatic failure, and acute hemolytic transfusion reactions, have been published (1). Today, however, machine apheresis procedures are more effective and safer for patients requiring exchange of cellular elements or plasma. Exchange transfusion is the most effective therapeutic procedure in the treatment of hemolytic disease of the newborn. Bilirubin removal prevents damage to the central nervous system caused by hyperbilirubinemia. In addition, sensitized erythrocytes are replaced by normally surviving cells and anemia is corrected. 

Treatment of patients with sickle cell anemia has led to disastrous sickling crises (99), and there are at present no clinical data to support the use of erythropoietin in sickle cell disease (100). 

The cost to society of sickle cell disease is high in terms of human suffering and in the financial burden of providing treatment to alleviate the pain and symptoms of the afflicted individnals and the loss of income to the individnals and their families and communities. Health problems due to sickle cell disease include chronic anemia, vaso-occlnsive crises, splenic sequestration, acute chest syndrome, stroke, splenic and renal dysfunction, and snsceptibility to bacterial infections (2,5,12). In Africa, treatments for sickle cell disease are limited... 

Congress thus may constitutionally fund sickle-cell anemia treatment centers across the country, even though 97% of persons with the disease are African American (Lee, 2001). Because this is a disease-, not race-, specific... 

Desferrioxamine (DFO-B), the natural siderophore initially isolated from Streptomyces pilosus, is the only iron chelator currently used for clinical treatment of iron-overload disease such as thalassemia, sickle cell anemia and hemochromatosis ° . ... 

As discussed above, in the case of phenylketonuria, early intervention can make the difference between mental retardation and a near normal life course for a newborn. Congenital adrenal hyperplasia and maple syrup urine disease are two examples of neonatal hereditary disorders where early diagnosis and medical intervention can make the difference between life and death for the newborn. In addition, in a number of genetic diseases, early diagnosis and treatment can help ameliorate symptoms these include fragile X syndrome, homocystinuria, sickle cell anemia, cystic fibrosis, and many /1-thalassemias. 

Among its many other applications, DNA fingerprinting is widely used for the diagnosis of genetic disorders. Cystic fibrosis, hemophilia, Huntington s disease, Tay-Sachs disease, and sickle-cell anemia are among the many diseases that can be detected, enabling early treatment of an affected child. In addition, the U.S. Department of Defense now requires blood and saliva samples from all military personnel. The samples are stored, and DNA is extracted should the need for identification of a casualty arise. 

The major problem with designing a small molecule to treat sickle cell anemia is not so much an issue of specificity, but arises from the treatment of a chronic disease. The potential cumulative toxicity from the amount of drug needed to interact with approximately two pounds of hemoglobin S over a homozygous patient s lifetime is the major concern (22) (for a review, see Vol. 3, Chapter 10. Sickle Cell Anemia, by Alan Schecter et al). 

In another letter to the editor (12) it was mentioned that the suspicion of partiality about the Committee on Toxicity becomes more plausible when one considers the issue of homocysteine. This intermediate metabolite may well turn out to be of greater importance as a risk factor for cardiovascular disease than cholesterol and blood pressure. Raised homocysteine concentrations appear to be accessible to treatment with pyridoxine (100 mg/day) together with vitamin B12 and foUc acid (13). Furthermore, the statement that there is no good evidence for the efficacy of pyridoxine in any disease, apart from depression, was criticized, because this ignores important studies in autism, pregnancy outcome, asthma, and sickle-cell anemia (12). 

A pharmacological role for vitamin E may exist in claudication arising from peripheral vascular disease. Studies with small numbers of patients having cystic fibrosis, glucose-6-phosphate dehydrogenase deficiency, and sickle cell anemia conditions associated with decreased erythrocyte half-lives showed that many had chemical evidence of vitamin E deficiency. Administration of vitamin E supplements (400-800 lU/d) significantly increased red cell survival time. Claims that doses of vitamin E 10-20 times the RDA are beneficial for treatment of skin disorders, fibrocystic breast disease, sexual dysfunction, cancer, baldness, and other disorders have not been substantiated. 

Initially, the focus of gene therapy was for the treatment of inherited disorders such as cystic fibrosis, sickle cell anemia, hemophilia, and adenosine deaminase deficiency. Gene therapy trials were later expanded to include patients with acquired diseases such as cancer and heart disease. 

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