Applications of Gene Therapy - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 273

132

140

112 117

116 116

120

108

101

96

95

100 89

85

82

80

68

67

51

60

40

37 38

40

14

20

8

2

1

0

Figure 6.2 Year-wise representation of the number of gene therapy clinical trials approved
worldwide.

of China approved the first ever adenoviral gene therapy treatment, Gendicine™,
infectious, replication-incompetent, engineered recombinant human adenoviral par-
ticles (rAd/ p53 ), composed of the adenoviral vector and the human wild-type p53
tumor suppressor gene, for the treatment of head and neck squamous cell carci-
noma (HNSCC), developed by Sio Biono Gene Tech [9] . Moreover, the State Food
and Drug Administration of China approved a second drug based on gene therapy,
Endostar, for treatment of cancerous tumors in the lungs and other organs [10] .
In 1999, gene therapy suffered from a major setback with the death of 18-year-old
Jesse Gelsinger, who was participating in a gene therapy trial for ornithine transcar-
boxylase deficiency (OTCD) [11] . Another major blow came in January 2000, when
the FDA placed a temporary halt on all gene therapy clinical trials using retrovi-
ral vectors because 2 out of 11 children treated in a French gene therapy trial had
developed a leukemia-like condition. These patients had been successfully treated
by gene therapy for X-linked severe combined immunodeficiency disease (X-SCID),
also known as “bubble baby syndrome” [12] . In April 2003, the FDA eased the ban
on gene therapy trials using retroviral vectors in blood stem cells. These incidents
placed a number of question marks on gene therapy using viral vectors and explored
the need of safe and effective vectors for gene therapy.
Since the first human gene therapy clinical trial in 1989, approximately 1579 clini-
cal trials have been completed, are ongoing, or have been approved, up to April 2010
( Fig. 6.2 ) in 28 countries. The vast majority of gene therapy clinical trials to date have
addressed cancer (64.5%), followed by CV disease (8.7%), and inherited monogenic
diseases (7.9%) ( Fig. 6.3 ). This may be because currently the first two are the leading
causes of mortality, and the last, involving the concept of replacing a well-defined defec-
tive gene with its correctly functioning counterpart, has an obvious appeal and rationale.