Clinical Studies With Recombinant-Dna-Derived Methionyl Human Growth Hormone in Growth Hormone Deficient Children

Abstract

Thirty-six children with growth hormone deficiency were treated for up to 48 months with methionyl human growth hormone (hGH) synthesised by DNA recombinant methods. The growth rate for these children increased from 3.2 +/- 1.1 cm/yr to 10.5 +/- 2.2 cm/yr (mean +/- SD). This was similar to the effect of pituitary hGH in ten GH deficient children, 3.8 +/- 1.0 to 10.1 +/- 1.1 cm/yr. Serum somatomedin C rose from 0.26 +/- 0.23 U/ml to 0.79 +/- 0.53 U/ml after 6 months of methionyl-hGH therapy, similar to the effect of pituitary hGH. The incidence of antibody formation to methionyl-hGH was higher than that observed with pituitary hGH (Kabi) but poor growth was observed only in the one patient on methionyl-hGH who acquired high-titre high-binding-capacity antibodies to hGH. No consistent changes in levels of antibodies to Escherichia coli proteins were detected. No other allergic manifestations or systemic side-effects were demonstrable.

Treatment of Pituitary Dwarfism with Authentic Recombinant Human Growth Hormone (SM-9500)

“…Therefore, the possibility that methionine residue itself is responsible for the production of antibodies cannot be completely denied. Until now there were three patients who showed growth attenuation probably due to hGH antibody obtained during mhGH treatment , Kaplan et al, 1986, Takano et al, 1986. Otherwise there were observed no side effects of mhGH treatment.…”

“…Since the success of methionyl-hGH (mhGH) synthesis by recombinant DNA technology (Goeddel et al, 1979), clinical trials for treating pituitary dwarfism have been performed (Takano et al, 1983, Kaplan et al, 1986, Bierich1986, Milner 1986, Girard and Gourmelen1986, Vicens-Calvet et al, 1986, Westphal1986, Takano et al, 1986. They reported the effectiveness of m-hGH similar to those of pituitaryderived human growth hormone (p-hGH).…”

Growth promoters in humans

“…It is an effective growth promoter in children and the only question over its use so far appears to be the fact that about 30% of children develop antibodies to G H and a smaller proportion develop antibodies to the organism uscd in its production, E. cofi. These antibodies do not appear to cause problems and do not affect growth rates in treated children (Kaplan et al 1986).…”

Considerations Related to the Use of Recombinant Human Growth Hormone in Children

“…The antibodies formed seem to have no clinical effects and do not form immune complexes. 43 Risks that have been attributed to human GH therapy include those associated with the physiological and psychological trauma related to years of regular injections. Certainly, this is one of the major stressors reported by diabetic patients related to their medical treatment.…”