Investigational agents for the treatment of growth hormone-insensitivity syndrome.
Growth hormone-insensitivity syndrome (GHIS) is usually caused by mutations in the growth hormone receptor. Recombinant IGF-I has been used to treat GHIS either alone (mecasermin) or in combination with IGF-binding protein (IGFBP)-3 (mecasermin rinfabate). IGF-I increases the growth velocity of children with IGF deficiency, which is either as a result of GHIS or an IGF-I gene deletion. Hypoglycaemia has been reported with administration of unbound IGF-I and, in addition, the serum half-life of unbound IGF-I is shorter when administered to patients with GHIS (who have low serum concentrations of its binding protein IGFBP-3) than when administered to normal volunteers or to patients with an IGF-I gene deletion (but normal IGFBP-3 levels). The IGF-I-IGFBP-3 combination was developed to prolong the half-life and counteract the acute adverse events (particularly hypoglycaemia) that are associated with administration of IGF-I. It seems that the IGF-I-IGFBP-3 combination has a longer half-life in patients with GHIS than unbound IGF-I, with fewer reports of adverse events (including hypoglycaemia) when administered to patients with diabetes. There are no studies comparing the efficacy of mecasermin with mecasermin rinfabate; both drugs have been shown to be effective but cannot be differentiated in terms of efficacy.
Kemp
Stephen F
SF
University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR 72202-3591, USA. KempStephenF@uams.edu
Thrailkill
Kathryn M
KM
D002648:Child; D015507:Drugs, Investigational / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D046150:Laron Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
D015507:Drugs, Investigational