Preclinical toxicity studies with two thymopoietin-like peptides

Area of Science:

• Immunology
• Peptide Chemistry
• Toxicology

Background:

• T-lymphocyte differentiation is regulated by thymopoietin, a polypeptide.
• Immunological activity resides in the Arg-Lys-Asp-Val-Tyr (32-36) fragment.
• This active fragment can be reduced to a tetrapeptide (RGH-0206) and a tripeptide (RGH-0205) while retaining activity.

Purpose of the Study:

• To assess the preclinical toxicity of RGH-0205 and RGH-0206.
• To determine the safety of these thymopoietin fragments for Phase I and II clinical trials.

Main Methods:

• Acute toxicity studies in mice, rats, and dogs with single 1000 mg/kg i.v. doses.
• 14-day repeated dose i.v. toxicity studies in Wistar rats (10-1000 mg/kg/day).
• 28-day repeated dose i.v. toxicity studies in Beagle dogs (6-60 mg/kg/day).

Main Results:

• No symptoms or damage observed in mice, rats, or dogs following single high-dose administration.
• Rats tolerated daily i.v. doses up to 1000 mg/kg for 14 days without adverse effects.
• Dogs tolerated daily i.v. doses up to 60 mg/kg for 28 days without adverse reactions.

Conclusions:

• RGH-0205 and RGH-0206 exhibit very low toxicity, likely due to their short in vivo half-life.
• The planned clinical dose of 1 mg/kg i.v. is considered safe for short-term administration of both peptides.