Applications of Gene Therapy - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 272

Table 6.1 Genetic and Acquired Diseases for Gene Therapy

Disease Defect

Severe combined immunodeficiency (SCID) Adenosine deaminase (ADA) deficiency

Cystic fibrosis Loss of cystic fibrosis transmembrane

conductance regulator ( CFTR )

Familial hypercholesterolemia Deficiency of low-density lipoproteins

(LDL) receptors

Hemophilia A and B Factors VIII and IX deficiency

Gaucher disease Glucocerebrosidase

Acquired immunodeficiency syndrome (AIDS) Suppressed immune system

Hemoglobinopathies thalassemias Structural defects in  and  globin gene

Hepatitis B Liver destruction

Inherited emphysema Lack of -1 antitrypsin

Muscular dystrophy Lack of dystrophin

Cancer Oncogenic factors and defects in tumor

suppression

Rheumatoid arthritis Autoimmune inflammation of joints

Neurological disorders (Parkinson's and
Alzheimer's)

Neurotransmitter release

Cardiovascular (restenosis, arteriosclerosis) Defects in blood vessels

However, the in vivo protocols are utilized when the target site and site of adminis-
trations is different, that is, a remote target site in the body. In this approach, the tis-
sue or cells require specific carriers (using targeting ligands or antibodies) to deliver
the genes [5,6] . There are numbers of human diseases, both genetic and acquired, for
which gene-based therapeutic approaches are gaining appraisals. Initially, gene ther-
apy arose with the aim of treating genetic diseases like CF, hemophilia, and hyper-
cholesterolemia. But as the base of gene therapy broadened, other human disorders
with genetic alternations have also been tried for treatment like rheumatoid arthritis,
various types of cancer, cardiovascular (CV) diseases, renal disorders, hepatic disor-
ders, acquired immunodeficiency syndrome (AIDS), severe combined immunodefi-
ciency (SCID) diseases, peripheral vascular diseases, some neurological conditions,
and so forth. However, the majority of human clinical trials conducted to date are
aimed at treating cancer. The various genetic and acquired disease targets for gene
therapy are summarized in Table 6.1 [7] .

6.1.2 Gene Therapy Clinical Trials—Current Status
Current gene therapy is experimental and has not proven to be very successful in
clinical trials. The United States Food and Drug Administration (USFDA) has
not yet approved any human gene therapy product for the market. In the first suc-
cessful human gene therapy clinical trial (1990 at the National Institute of Health,
USA), a 4-year-old girl was treated for SCID, paving the pathway for other poten-
tial genetic-level treatments [8] . In 2003, the State Food and Drug Administration