CJC-1295 DAC Peptide (5MG)

Growth hormone–releasing hormone (GHRH) deficiency causes proportionate dwarfism and pituitary hypoplasia due to reduced somatotroph proliferation. While recombinant GH therapy remains the primary treatment for GH deficiency, it does not replicate natural pulsatile GH secretion. Conventional GHRH animal research showed limitations by its short plasma half-life, requiring multiple daily injections or continuous infusion. Previous GHRH analogs failed to normalize growth even with twice-daily dosing. The present study addressed these challenges by testing a long-acting GHRH analog, CJC-1295, to evaluate whether it could normalize growth and body composition in GHRH knockout (GHRHKO) mice, and to determine the minimal effective dosing interval.

CJC-1295 is a synthetic GHRH analog designed for prolonged biological activity. Unlike traditional short-acting GHRH peptides, CJC-1295 covalently binds to endogenous albumin, forming a drug-affinity complex (DAC) that extends its half-life to match that of albumin. This albumin binding mechanism allows sustained GHRH receptor activation and prolonged GH release. As a long-acting GHRH analog, CJC-1295 represents a new generation of growth hormone–releasing hormone (GHRH) analogs designed to overcome rapid enzymatic degradation and short systemic residence time observed in earlier peptides. Previous CJC-1295 studies in animals showed prolonged elevations in serum GH and IGF-1 after administration, validating its pharmacological design.

Researchers used male GHRH knockout (GHRHKO) mice, which lack endogenous GHRH production, and heterozygous (HTZ) littermates as normal controls. Groups and dosing:

• CJC-1295 administered subcutaneously at 2 µg every 24 h, 48 h, or 72 h for 5 weeks.
• Placebo groups: GHRHKO + vehicle and HTZ + vehicle.

Measured outcomes:

• Body metrics: weight, naso-anal length, femur and tibia lengths.
• Body composition: lean mass, visceral fat, and subcutaneous fat percentages.
• Pituitary assessment: total RNA yield, GH and prolactin mRNA via Northern blot, GH protein via Western blot, and immunohistochemistry for somatotroph proliferation.
• Serum IGF-1: determined at study termination to evaluate systemic anabolic effects.

Growth normalization: Daily CJC-1295 (24 h dosing) fully normalized body weight, naso-anal length, and femur/tibia lengths—matching normal HTZ mice. Partial improvements with reduced frequency: 48 h dosing produced intermediate effects with normal bone length but submaximal total growth. 72 h dosing improved growth compared to placebo but did not achieve full normalization. Pituitary and RNA data: Total pituitary RNA increased 13-fold, 9-fold, and 7-fold in 24 h, 48 h, and 72 h groups, respectively. GH mRNA rose proportionally (11-, 8-, and 6-fold increases) and was supported by higher GH protein expression. Cellular effects: Immunohistochemistry confirmed significant somatotroph cell proliferation, while prolactin cell changes were minimal. Serum IGF-1: Only daily administration significantly elevated circulating IGF-1 levels. Less frequent dosing showed no statistical increase, correlating with diminished growth response.

This study provides pivotal evidence for optimizing CJC-1295 routes of administration in experimental models. It demonstrates that administration frequency strongly influences growth outcomes, confirming that daily dosing maintains physiological GH and IGF-1 signaling. The findings advance the understanding of CJC-1295 studies by establishing the relationship between injection interval, peptide bioavailability, and biological response. Moreover, the albumin-binding DAC design underscores how structural modifications can enhance peptide stability and extend systemic exposure—principles applicable to future GHRH analog development and dosing research.

Once-daily administration of CJC-1295 successfully normalized growth and body composition in GHRHKO mice by restoring pituitary GH production and elevating IGF-1 levels. Dosing every 48 h or 72 h yielded partial results, emphasizing that administration frequency determines therapeutic success. The study highlights the translational potential of long-acting GHRH analogs in peptide research and supports future investigations into dose optimization and pharmacokinetics across species. Proper dosing intervals are essential for maintaining consistent biological activity and mimicking physiological GH release patterns.