Acta Biochim Biophys Sin (2008) | Volume 40 | Issue 7 | Page 636 Immunotherapeutic drugs and vaccines for multiple sclerosis Acta Biochim Biophys Sin (2008): 636-642 | © 2008 Institute of Biochemistry and Cell Biology, SIBS, CAS | All Rights Reserved 1672-9145 http://www.abbs.info; www.blackwellpublishing.com/abbs | DOI: 10.1111/j.1745-7270.2008. 00444.x Towards immunotherapeutic drugs and vaccines against multiple sclerosis Maria Katsara 1,2 , John Matsoukas 2 , George Deraos 2 , and Vasso Apostolopoulos 1 * 1 Burnet Institute, Austin Campus, Immunology and Vaccine Laboratory, Studley Road, Heidelberg, Victoria 3084, Australia 2 Department of Chemistry, Section of Organic Chemistry, Biochemistry, and Natural Products, University of Patras, Patras 26500, Greece Received: May 10, 2008 Accepted: May 17, 2008 This work was supported by grants from the Ministry of Development Secretariat of Research and Technology of Greece (Grant Aus. 005) and Du Pré grant from the Multiple Sclerosis International Federation to MK, and a National Health and Medical Research Council of Australia R. Douglas Wright Fellowship (223316) to VA *Corresponding author: Tel, 613-92870666; Fax, 613-92870600; E- mail, vasso@burnet.edu.au Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. Numerous treatment options are available to MS patients; however, these options need to be improved. Herein, we review the current drugs and therapeutic approaches available to MS patients, preclinical trial interventions and recent animal model studies for the potential therapy of MS. Since the current treatment of MS remains elusive and is limited, animal studies and clinical research offers an optimistic outlook. Keywords multiple sclerosis; MS treatment; immuno- suppressive drugs; immunomodulatory drugs; MS clinical trials; peptides; altered peptide ligand The World Health Organization (WHO) estimates that over 2.5 million people globally suffer from multiple sclerosis (MS) [1]. With the present global population growing to an unprecedented height of 6.5 billion in 2005 and anticipated to reach 7.6 billion by 2020, the prevalence and onset of MS in children and particularly adults is expected to rise exponentially [2]. It is estimated that approximately 400,000 people suffer from MS in the US, with 500,000 Europeans and 18,000 Australians also with the disease (h t t p : / / w w w . m s a u s t r a l i a . o r g . a u ). T cell recognition of self myelin peptides presented by major histocompatibility complex (MHC) class II is involved in autoimmune attack in the human disease multiple sclerosis. MS is a chronic, autoimmune disease of the central nervous system [3]. T cells, B cells, macrophages and microglia migrate through the disrupted blood brain barrier which induce inflammation, demyelination and neurodegeneration [3]. Some of the proteins involved in this destruction include myelin oligodendrocyte glycoprotein, proteolipid protein and myelin basic protein (MBP). Depending on the temporal profile and neurological findings of the patient, there are four distinct subtypes of the disease characterized by increasing severity: (1) relapsing/remitting MS (RRMS), (2) secondary progressive MS (SPMS), (3) primary progressive MS (PPMS) and (4) progressive relapsing MS (PRMS) [4,5]. More than 80% of MS patients are classified as having RRMS at onset of the disease, and 50% of those will develop SPMS after 10−15 years of disease progression. Approximately, 15% of MS patients develop PPMS, and only 5% of these patients will develop (PRMS) [4.5]. The therapeutic approach to MS has three dimensions: (1) management of acute phase of the disease, (2) prophylactic treatment, which includes specific and non-specific immuno- modulatory and immunosuppressive agents, and (3) drugs for the symptoms such as tiredness, spasticity, shakiness of limps and chronic pain. Although there is no definitive treatment of MS, new clinical and animal studies give promise and optimism in developing new drugs for MS. Current Therapies for MS––Drugs Current peptide therapies of MS are relatively immature, with only a handful of products available on the market which mainly include treatment with immunomodulatory agents. The interferons available are Schering AG’s Betaferon/Betaseron (IFNβ-1b), Biogen’s Avonex (IFNβ- 1a), Serono/Pfizer’s Rebif (IFNβ -1a) [2,3], Teva’s Copaxone ® (copolymer glatiramer acetate) [6], Amgen/ Serono’s (Novantrone ® ) (mitoxantrone) [7], azathioprine [8], cyclophosphamide (Endoxan ® ) and more recently, the a 4 -integrin antagonist (Natalizumab ® ) [7]. These drugs aim to downregulate the autoimmune attack to MS following Review