Venom Peptide-Steroid Conjugate Effective in Collagen Induced Arthritis Save

Science Translational Medicine features a report from the Fred Hutchinson Cancer Research Center showing that a scopion venom peptide, coupled to steroid, can significantly reduce joint inflammation in a rat model of rheumatoid arthritis (RA).

Using a peptide shown to traffic to joint cartilage, researchers systemically treated rodents with collagen-induced arthritis, with a conjugate of the peptide with steroid, suggesting that such a conjugate has the potential for joint-targeted therapy.

Cystine-dense peptides (CDPs) were shown to distribute to cartilage of the knees, ankles, hips, shoulders, and intervertebral discs, achieving peak concentration in cartilage within 30 min (after after systemic administration) and remained detectable for >4 days.

CDPs are miniproteins defined by having at least three disulfide bonds (cystines) in a protein that is typically 20 to 60 amino acids in length. CDPs may be found in the venom of spiders, snakes, scorpions and a wide variety of other species, including plants, fungi, bacteria, marine mollusks, and insects. 

In these studies they used, CDP-11R, that was shown to distribute (by fluorophore imaging) to joint cartilage when coupled with either dexamethasone or triamcinolone acetonide (TAA).

The CDP-11R–TAA conjugate was superior in alleviating joint inflammation in the rat collagen–induced model while avoiding toxicities.

This conjugate shows promise for clinical development and establishes proof of concept for multijoint targeting of disease-modifying therapeutic payloads.