C-Type Natriuretic Peptide Analogs: Current and Future Therapeutic Applications.

BACKGROUND

Short stature is one of the most common reasons for referral to a pediatric endocrinologist that can be due to multitude of conditions, including an ever-growing list of genetic etiologies. Despite the numerous different causes, options for medical therapy remain quite limited, with the primary medication available being recombinant human growth hormone. A second option is recombinant insulin-like growth factor 1 (rIGF-1) in select patients with severe primary IGF-1 deficiency. Alternative strategies to increase height have been attempted such as delaying the onset of puberty with a gonadotropin-releasing hormone agonist or delaying epiphyseal fusion with an aromatase inhibitor. However, these options focus on increasing the duration of growth as opposed to directly stimulating growth at the growth plate.

SUMMARY: Novel approaches to growth promotion have recently been developed, including analogs of C-type natriuretic peptide (CNP). The purpose of this study is to review the function of CNP and its potential use in different conditions.

KEY MESSAGES: Alterations in the CNP/FGFR3 pathway can lead to multiple defined genetic causes of short stature. The CNP pathway has become the focus for treatment of children with short stature that suffer from such genetic conditions, with promising outcomes.