¹Zycos Inc, Lexington, MA, USA

Correspondence: ML Hedley, Zycos, Inc., 44 Hartwell Avenue, Lexington, MA 02421, USA

The first two authors contributed equally to this work

Received 29 May 2002; Accepted 22 August 2002.

Abstract

Melanocyte-stimulating hormone (MSH) is a 13 amino acid peptide with potent anti-inflammatory effects. We created two DNA expression constructs (miniPOMC and pACTH1–17) that encode bioactive versions of the MSH peptide, and tested these constructs for therapeutic effects in experimental autoimmune encephalomyelitis (EAE). Each construct contained the sequences for MSH, as well as the sequences that are involved in the secretion and processing of the POMC gene with the assumption that these sequences would promote processing and release of the encoded MSH peptide. The differences between the two constructs lie at the C-terminal end where amino acids necessary for amidation of MSH were included in only the pACTH1–17 construct. These two constructs were tested in vitro in bioassays, and in vivo in a mouse model of EAE. The results show that although bioactive peptides are secreted from cells transfected with either construct, there appears to be a significant therapeutic effect only with the pACTH1–17 construct which contains the extra C-terminal amino acids. The data suggest that it is possible to engineer DNA expression vectors encoding small secreted peptides such as MSH, and that similar type constructs may be useful as therapeutics for the treatment of inflammatory diseases.