Mecasermin (recombinant human insulin-like growth factor I).
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Rosenbloom AL
Mecasermin (recombinant human insulin-like growth factor I).
Adv Ther. 2009 Jan;26(1):40-54. doi: 10.1007/s12325-008-0136-5. Epub 2009 Jan 28.
- PubMed ID
- 19198769 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Mecasermin Cation-independent mannose-6-phosphate receptor Protein Humans UnknownNot Available Details Mecasermin Insulin receptor Protein Humans UnknownNot Available Details Mecasermin Insulin-like growth factor 1 receptor Protein Humans YesAgonistDetails Mecasermin rinfabate Cation-independent mannose-6-phosphate receptor Protein Humans UnknownNot Available Details Mecasermin rinfabate Insulin receptor Protein Humans UnknownNot Available Details Mecasermin rinfabate Insulin-like growth factor 1 receptor Protein Humans YesAgonistDetails