Growth hormone (GH) exercises its growth effects by stimulating
insulin-like growth factor I (
IGF-I) synthesis in the liver (endocrine
IGF-I) and by inducing chondrocyte differentiation/replication and local production of
IGF-I (paracrine/autocrine
IGF-I).
Injectable recombinant human (rh)
IGF-I (
mecasermin) has been available for nearly 20 years for treatment of the rare instances of GH insensitivity caused by GH receptor defects or GH-inhibiting
antibodies. Full restoration of normal growth, as occurs with rhGH replacement of GH deficiency, is not seen, presumably because only the endocrine deficiency is addressed. RhIGF-I has also been effective as an
insulin-sensitizing agent in severe
insulin-resistant conditions. Although the
insulin-sensitizing effect may benefit both type 1 and
type 2 diabetes, there are no ongoing clinical trials because of concern about risk of retinopathy and other complications. Promotion of rhIGF-I for treatment of idiopathic short stature has been intensive, with neither data nor rationale suggesting that there might be a better response than has been documented with rhGH. Other applications that have either been considered or are undergoing clinical trial are based on the ubiquitous tissue-building properties of
IGF-I and include chronic
liver disease,
cystic fibrosis, wound healing,
AIDS muscle wasting,
burns,
osteoporosis,
Crohn's disease,
anorexia nervosa,
Werner syndrome,
X-linked severe combined immunodeficiency,
Alzheimer's disease,
muscular dystrophy,
amyotrophic lateral sclerosis,
hearing loss prevention,
spinal cord injury, cardiovascular protection, and prevention of
retinopathy of prematurity. The most frequent side effect is
hypoglycemia, which is readily controlled by administration with meals. Other common adverse effects involve
hyperplasia of lymphoid tissue, which may require
tonsillectomy/
adenoidectomy, accumulation of body fat, and coarsening of
facies. The anti-apoptotic properties of
IGF-I are implicated in
cancer pathogenesis-a concern for long-term
therapy. It is unlikely that
mecasermin will be useful beyond the orphan indications of severe
insulin resistance and GH insensitivity.