Therapeutic hormones - Pharmaceutical Biotechnology: Concepts and Aapplications - page 312

neurological disorder) was discovered. In this year, a young man, who had received hGH therapy
some 15 years previously, died from CJD, which, investigators concluded, he had contracted
from infected pituitary extract (CJD appears to be caused by a prion). At least an additional
12 CJD cases suspected of being caused in the same way have subsequently been documented.
Fortunately, several recombinant hGH (rhGH) preparations were coming on-stream at that time
(Table 11.7), and now all hGH preparations used clinically are derived from recombinant sources.
Currently, in excess of 20 000 people are in receipt of rhGH therapy.
rhGH was fi rst produced in E. coli in the early 1980s. The initial recombinant preparations dif-
fered from the native human hormone only in that they contained an extra methionine residue (due
to the AUG start codon inserted at the beginning of the gene). Subsequently, a different cloning
strategy allowed production in E. coli of products devoid of this terminal methionine.
In vitro analysis, including tryptic peptide mapping, amino acid analysis and comparative im-
munoassays, shows the native and recombinant forms of the molecule to be identical. Clinical
trials in humans have also confi rmed that the recombinant version promotes identical biological
responses to the native hormone. rhGH was fi rst purifi ed (on a laboratory scale) by Genentech
scientists using the strategy outlined in Figure 11.9. A somewhat similar strategy is likely used in
its process-scale purifi cation.

11.5 The gonadotrophins

The gonadotrophins are a family of hormones for which the gonads represent their primary tar-
get (Table 11.8). They directly and indirectly regulate reproductive function and, in some cases,
the development of secondary sexual characteristics. Insuffi cient endogenous production of any

Table 11.7 rhGH preparations approved for general medical use

Product (tradename) Company Indication

Humatrope Eli Lilly hGH defi ciency in children

Nutropin Genentech hGH defi ciency in children

Nutropin AQ Schwartz Pharma AG Growth failure, Turner's syndrome

BioTropin Biotechnology General hGH defi ciency in children

Genotropin Pharmacia & Upjohn hGH defi ciency in children

Saizen Serono Laboratories hGH defi ciency in children

Serostim Serono Laboratories Treatment of AIDS-associated

catabolism/wasting

Norditropin Novo Nordisk Treatment of growth failure in

children due to inadequate
growth hormone secretion

Omnitrop Sandoz Treatment of children and adults

with certain forms of growth
disturbance

Valtropin Biopartners Treatment of children and adults

with certain forms of growth
disturbance

Somavert (hGH analogue, i.e.
antagonist)

Pharmacia Treatment of selected patients

suffering from acromegaly