Enhancing protective effects of modified peptides for treatment of multiple sclerosis

Moxey, Nancy, Trifilieff, Elisabeth and Greer, Judith (2010). Enhancing protective effects of modified peptides for treatment of multiple sclerosis. In: ISNI 2010 Abstracts: 2010 10th Course of the European School of Neuroimmunology. 10th Course of the European School of Neuroimmunology, Sitges, Spain, (92-92). 26-30 October 2010. doi:10.1016/j.jneuroim.2010.08.001


Author Moxey, Nancy
Trifilieff, Elisabeth
Greer, Judith
Title of paper Enhancing protective effects of modified peptides for treatment of multiple sclerosis
Conference name 10th Course of the European School of Neuroimmunology
Conference location Sitges, Spain
Conference dates 26-30 October 2010
Proceedings title ISNI 2010 Abstracts: 2010 10th Course of the European School of Neuroimmunology   Check publisher's open access policy
Journal name Journal of Neuroimmunology   Check publisher's open access policy
Place of Publication Amsterdam, Netherlands
Publisher Elsevier
Publication Year 2010
Sub-type Published abstract
DOI 10.1016/j.jneuroim.2010.08.001
Open Access Status Not Open Access
ISSN 0165-5728
1872-8421
Volume 228
Issue 1-2
Start page 92
End page 92
Total pages 1
Language eng
Abstract/Summary Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system. Current treatments for MS are nonspecific in their action and have significant side effects on normal immune function. Antigenspecific immunotherapeutic agents that change the response of pathogenic CD4+ T cells could help to reduce these side effects. The best way to target these cells specifically is to use modified peptides to target the interaction between the T cell receptor and the MHC; however, peptide-based reagents typically are poorly immunogenic. Our work aims to enhance the bioavailability and effectiveness of immunomodulatory peptides that modulate CD4+ T cells and have potential therapeutic application inMS.We have used a well established altered peptide ligand (APL) model that has been shown to be therapeutically effective in experimental autoimmune encephalomyelitis (EAE) to test the efficacy of our approach. Myelin proteolipid protein (PLP)-specific APL was modified by attaching palmitic acid via a thioester bond to a cysteine residue of the peptide. The ability of these thiopalmitoylated (S-palm) APL to modulate pathogenic immune responses in vitro and show clinical efficacy in an SJL/J mouse model of MS was then compared with that of nonacylated APL and controls. The serum half-life of S-palm APL was approximately 20-fold longer than that of APL alone. Furthermore S-palmAPL induced stronger proliferative responses than APL, induced greater numbers of regulatory Tcells (N15% difference), and induced a 10-fold increase in the production of the anti-inflammatory cytokine interleukin 10 (IL-10) compared to APL alone. Therapeutically, S-palmAPL used at a 50-fold lower concentration was as effective as APL in preventing disease in the animal model. In addition, S-palmAPL was also more effective at treating established disease, resulting in full recovery 3–5 days sooner than APL treated mice. S-palm APL retain and improve on the beneficial effects of APL, both in vitro and in vivo, and have good potential as a method to enhance the therapeutic effects of specific peptide-based agents in diseases such as MS.
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Conference Paper
Collection: UQ Centre for Clinical Research Publications
 
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Created: Sun, 23 Jan 2011, 10:03:19 EST