More MS news articles for Mar 2002

DDB-202: A New Therapeutic Approach in the Treatment of Multiple Sclerosis using Myelin Basic Protein Peptide Analogues

http://www.bioportfolio.com/news/dyodelta_1.htm

London, 18 March 2002

DyoDelta Biosciences Ltd announced today that it entered into a collaboration for the exclusive license of a novel proprietary pharmaceutical compound programme developed by Professor John Matsoukas, Head of Medicinal Chemistry at the University of Patras in Greece.  The lead compound DDB-202, is at the forefront of modern approaches towards the therapeutic management of Multiple Sclerosis (MS) that involve the design and use of peptide analogues of disease-associated myelin epitopes to induce peripheral T cell tolerance.  MBP (Myelin Basic Protein) is one of the candidate autoantigens in MS and DDB-202 is designed as an analogue of MBP’s most immunodominant region in human MS, therefore conferring an expected immunomodulatory activity and is hoped to be used to prevent and treat this debilitating disease.

The use of peptides as therapeutic entities has been attempted unsuccessfully so far due to their sensitivity to proteolytic enzymes.  DDB-202 is a stable MBP epitope peptide molecule with the same biological activity as other unstable molecules.  In addition to efficacy shown in experimental allergic encephalomyelitis (EAE) models of multiple sclerosis, there is evidence that DDB-202 induces the production of IL-10 by T-cells from MS patients.

Dimitri F. Dimitriou, CEO of DyoDelta Biosciences commented: “We are delighted to gain access to a compound with such qualities that could become a useful treatment for MS.  We know a few other companies have used similar MBP approaches but to our knowledge, DDB-202 seems to have solved many the issues with this chemistry, including the stability problems that others have faced.”

Prof Matsoukas said: "I am very excited to see that years of research at my labs are coming to fruition.  Following the remarkable stability and efficacy of DDB-202 in animal models and in vitro with human T cells, this forms the basis for DDB-202 to proceed to clinical trials in the near future."

DyoDelta Biosciences is seeking development partners for DDB-202.

DyoDelta Biosciences Ltd is London-based company, focusing on exploiting opportunities in the Life Sciences.

Providing broad "bio-incubator" services, DyoDelta Biosciences creates value by progressing the development of novel compounds and research know-how through collaborations.  The developments in the pharmaceutical industry over the past years, have resulted in a number of niche companies specialising in different parts of drug development and commercialisation, effectively covering all industry components.  DyoDelta Biosciences facilitates the progression of assets through partnering, all the way to the stage whereby they can eventually be marketed by major pharmaceutical companies on a global basis.

DyoDelta Biosciences also guides and supports pharma and biotech companies in creating partnerships with others, in an integrated way, including: identification of potential partners, initiation of contacts, commercial and technical evaluation of opportunities, M&A activities, negotiations of terms, contract reviews and preparation (with DyoDelta's legal contacts) and issues arising out of existing collaborations.

Contact for further information

Dimitri F. Dimitriou
Chief Executive Officer
DyoDelta Biosciences Ltd
Berkeley Square House
Berkeley Square
London W1J 6BD
UK

Tel +44 20 7396 5572
Fax +44 20 7396 5599

Email: dimitri.dimitriou@dyodelta.com

Website: http://www.dyodelta.com

Relevant Publications

1) L. Kappos, G Comi, H. Panitch, J. Oger, J. Antel, P. Conlon, L. Steinman & The Altered Peptide Ligand in relapsing MS study group.

Induction of a non-encephalitogenic type 2 T helper-cell antoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo controlled, randomized phase II trial.

Nature Medicine, 2000, 6(10): 1176-1182.

2) B. Bielekova, B. Goodwin, N. Richert, I. Cortese, T. Kondo, G. Afshar, B. Gran, J. Eaton, J. Antel, J. Frank, H. McFarland, R. Martin.

Encephalitogenic potential of the myelin basic protein peptide (amino-acids 83-99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand.

Nature Medicine, 2000, 6(10): 1167-1171.

3) J. Pires, T. Tselios, J. Matsoukas, G. Moore.

Role of myelin basic protein epitope MBP74-85 in experimental autoimmune encephalomyelitis: elaboration of agonist and antagonist motifs.

Drug Development Research, 1999, 48: 1-5.

4) T. Tselios, L. Probert, I. Daliani, E. Matsoukas, A. Troganis, I. Gerothanasis, T. Mavromoustakos, G. Moore, J. Matsoukas.

Design and synthesis of a potent cyclic analogue of the myelin basic protein epitope MBP72-85: importance of the ala81 carboxyl group and of a cyclic conformation for induction of experimental allergic encephalomyelitis (E.A.E.).

J. Med. Chem., 1999, 42, 7:1170-1177.

5) T. Tselios, I. Daliani, L. Probert, S. Deraos, E. Matsoukas, S. Roy, J. Pires, G. Moore, J. Matsoukas.

Treatment of experimental allergic encephalomyelitis (EAE) induced by guinea pig myelin basic protein epitope 72-85 with a human MBP87-99 analogue and effects of cyclic peptides.

Bioorg. Med. Chem., 2000, 8: 1903-1909.

6) T. Tselios, I. Daliani, S. Deraos, S. Thymianou, E. Matsoukas, A. Troganis, I. Gerothanassis, A. Mouzaki, T. Mavromoustakos, L. Probert, J. Matsoukas.

Treatment of experimental allergic encephalomyelitis (EAE) by a rationally designed cyclic analogue of myelin basic protein (MBP) epitope 72-85.

Bioorg. Med. Chem. Lett., 2000, 10: 2713-2717.

7) T. Tselios, V. Apostolopoulos, I. Daliani,, S. Deraos, S. Grdadolnik, T. Mavromoustakos, M. Melachrinou, S. Thymianou, L. Probert, A. Mouzaki, J. Matsoukas.

Antagonistic Effects of Human Cyclic MBP87-99 Altered Peptide Ligands in Experimental Allergic Encephalomyelitis and Human T-Cell Proliferation.

J. Med. Chem. 2002, 45, 275-283.

Disease Overview

Multiple sclerosis (MS) is a chronic, potentially debilitating disease potentially of autoimmune origin, that affects the central nervous system.  In MS, natural defences like antibodies and white blood cells attack proteins in the myelin sheath surrounding nerves in the brain and spinal cord, causing inflammation and injury to the sheath and ultimately to the nerves.  This results in multiple areas of scarring (sclerosis), affecting muscle coordination, visual sensation and other nerve signals.  MS is a progressive disease and is generally diagnosed first in people between the ages of 20 and 40.  Estimates range from 1 million to 2.5 million people affected with MS worldwide, with a market of around $11 billion.  The disease is poorly understood.
 

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