Nucleic-acid- and cell-based therapeutics - Pharmaceutical Biotechnology: Concepts and Aapplications - page 441

• Some genetic diseases are quite complex, with several organs/cell types being affected. In most

instances, it has proven diffi cult in practice to introduce the required gene into all the affected
cell types.

• Regulation of expression levels of the genes transferred has proven problematic.

• Drug companies often display greater interest in applying gene therapy to more prevalent dis-

eases, such as cancer. The patient population suffering from many genetic diseases is relatively
modest. In some instances, a limited patient population may not be suffi cient to allow the devel-
oping company to recoup the cost of drug development.

Some of the genetic conditions for which the defective gene has been pinpointed are summa-
rized in Table 14.4. Many of the initial attempts to utilize gene therapy in practice focused upon
haemoglobinopathies (e.g. sickle cell anaemia and thalassaemias). These conditions were amongst
the fi rst genetic disorders to be characterized at a molecular level, with the defect centring around
the haemoglobin α- or β-chain genes. Furthermore, the target cells in the bone marrow could be
removed and subsequently replaced with relative ease. However, these conditions proved to be a
diffi cult initial choice for the gene therapist. The production of the appropriate quantities of func-
tional haemoglobin is dependent not only upon the presence of

α - and β -globin genes of the correct

Table 14.4 Some examples of genetic diseases for which the defective gene
responsible has been identifi ed

Disease Defective genes protein product

Haemophilia A Factor VIII

Haemophilia B Factor IX

Thalassemia β-globin

Sickle cell anaemia β-globin

Familial hypercholesterolaemia Low-density protein receptor

Severe combined immunodefi ciency Adenosine deaminase

Severe combined immunodefi ciency Purine nucleoside phosphorylase

Niemann-Pick disease Sphingomylinase

Gaucher's disease Glucocerebrosidase

Cystic fi brosis Cystic fi brosis transmembrane regulator

Emphysema α 1 -Antitrypsin

Leukocyte adhesion defi ciency CD18

Hyperammonaemia Ornithine transcarbamylase

Citrullinaemia Arginosuccinate synthetase

Phenylketonuria Phenylalanine hydroxylase

Maple syrup disease Branched chain α-ketoacid dehydrogenase

Tyrosinaemia type 1 Fumarylacetoacetate hydrolase

Glycogen storage defi ciency type 1A Glucose-6-phosphatase

Fucosidosis α-L-Fucosidase

Mucopolysaccharidosis type VII β-Glucuronidase

Mucopolysaccharidosis type I α-L-Iduronidase

Galactosaemia Galactose-1-phosphate uridyl transferase