Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse

Summary

Animal study in mice lacking the GHRH gene (GHRH knockout), testing whether CJC-1295 can restore normal growth. CJC-1295 is a synthetic GHRH analog that selectively and covalently binds to albumin after injection, extending its half-life and duration of action. The authors note that GHRH’s very short half-life limits its use as a therapy. In their earlier work, even twice-daily injections of a GHRH analog did not normalize growth in these mice. Here, once-daily CJC-1295 did normalize growth and body composition, while dosing every 48 or 72 hours was less effective.

Key Findings

• Knockout mice given CJC-1295 daily had normal body weight and length
• Mice dosed every 48 or 72 hours grew more than placebo-treated mice but did not reach full growth normalization
• Femur and tibia length stayed normal with dosing every 24 or 48 hours
• Relative lean mass and subcutaneous fat mass were normal in all treated groups
• CJC-1295 increased total pituitary RNA and GH mRNA, suggesting proliferation of GH-producing (somatotroph) cells, which immunohistochemistry confirmed

Methodology

Three groups of 1-week-old GHRH knockout mice were treated for 5 weeks with 2 µg of CJC-1295 given every 24, 48 or 72 hours. Placebo-treated knockout mice and mice heterozygous for the knockout allele served as controls. Outcomes were body weight and length, femur and tibia length, lean and fat mass, pituitary RNA and GH mRNA, and pituitary immunohistochemistry.

Limitations

• Mouse study in a genetic model of GH deficiency; it does not show effects in healthy adult humans
• Group sizes are not reported in the abstract
• The abstract does not report circulating GH or IGF-I levels
• Treatment covered 5 weeks of early growth; no long-term safety data
• Only the long-acting, albumin-binding CJC-1295 was tested; results should not be assumed to carry over to short-acting “no-DAC” products

Relevance to Content

Preclinical evidence that CJC-1295 works through the pituitary, stimulating GH-producing cells. In this model dosing frequency mattered: once daily normalized growth, every 2-3 days did not fully. Useful background on how a long-acting GHRH analog acts, but it is animal data and not evidence of effects in adults.

See Also

• Parent compound: CJC-1295
• Sermorelin
• Tesamorelin