Table 6.
Experimental therapies for MS as tested in EAE.
| Therapeutic approach | Proposed mechanism of action | References |
|---|---|---|
| Gene therapy | Furlan et al. (2003) | |
| - IL-4 | Inhibits Th1 cell activation. | Broberg et al. (2004), Butti et al. (2008) |
| - IFN-β | Inhibits local autoimmune reaction in the CNS. | Makar et al. (2008a) |
| Stem cell transplantation | Scolding (2006) | |
| - Mesenchymal stem cells | Modulate T cell function, decrease IL-17 via IL-23 secretion. | Pedemonte et al. (2007), Wang et al. (2008) |
| - Neural stem cells | Down-regulate inflammation, stimulate the endogenous brain repair system. | Aharonowiz et al. (2008), Einstein et al., 2006, Einstein et al., 2009, Martino and Pluchino (2007), Pluchino and Martino (2008) |
| Neurotrophic factors | Mirowska-Guzel (2009) | |
| - BDNF | Reduces inflammation and apoptosis. | Makar et al. (2008b) |
| - Erythropoietin | Activates the neuroprotective phosphatidylinositol 3-kinase/Akt pathway, down-regulates glial MHC class II. | Agnello et al. (2002), Sättler et al. (2004), Yuan et al. (2008) |
| Monoclonal antibodies | Buttmann and Rieckmann (2008), Lutterotti and Martin (2008), Rose et al. (2008) | |
| Natalizumab | Anti-CD49d inhibits lymphocyte adhesion. | Rice et al. (2005), Stüve and Bennett (2007) |
| Anti-cytokines | Small molecular weight drug suppresses pro-inflammatory cytokines. | Karpus et al. (2008) |
| CRYAB | Stress protein αB-crystallin has an anti-inflammatory effect. | Ousman et al. (2007) |
| Beta-lactam antibiotic | Ceftriaxone modulates myelin antigen presentation and impairs antigen-specific T cell migration into the CNS. | Melzer et al. (2008) |
| Steroids | Estradiol and progesterone increase BDNF and myelination. | Garay et al. (2008) |
| Statins | 3-Hydroxy-3-methylglutaryl-coenzymeA-reductase inhibitors prevent geranyl-geranylation of RhoA GTPase and its tethering to the membrane and thereby inhibit T cell activation and infiltration into the CNS. | Aktas et al. (2003), Mix et al. (2006), Stanislaus et al. (1999), Waiczies et al. (2008), Youssef et al. (2002) |
| Fingolimod (FTY720) | Sphingosine-1-phosphate agonist reduces systemic T and B cell response as well as auto-reactive T cells in the CNS and it promotes remyelination by stimulation of ODC function. | Balatoni et al. (2007), Foster et al. (2009), Kappos et al. (2006b), Miron et al., 2008, Miron et al., 2010, Papadopoulos et al. (2010) |
| Fumarate (BG-12) | Fumaric acid esters increase the anti-inflammatory cytokine IL-10. | Schilling et al. (2006) |
| Minocycline | Inhibits matrix metalloproteinases and thereby T cell transmigration. | Brundula et al. (2002) |
| Gemfibrozile, fenofibrate, ciprofibra | Peroxisome proliferator-activated receptor (PPAR)-α agonists increase the anti-inflammatory cytokine IL-4. | Lovett-Racke et al. (2004) |
| Laquinimod | Linomide-derivative ABR-215062 changes the cytokine balance towards the anti-inflammatory cytokines IL-4, IL-10 and TGF-β | Brunmark et al. (2002), Comi et al. (2008), Runström et al. (2006), Wegner et al. (2009), Yang et al. (2004) |
| AICAR | Protein kinase A activating 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside inhibits the pro-inflammatory cytokines IFN-γ and TNF-α and induces the anti-inflammatory cytokines IL-4 and IL-10. | Nath et al. (2005) |
| CYLA | Calpain inhibitor reduces inflammatory infiltration, demyelination and axonal injury. | Hassen et al. (2008) |
| 3,4-DAA | Derivative of tryptophan metabolite N-(3,4,-Dimethoxycinnamoyl) anthranilic acid inhibits pro-inflammatory cytokines. | Platten et al. (2005) |
| EGCG | Green tea constituent (−)-epigallocatechin-3-gallate blocks proteasome complex, proliferation and TNF-α production of encephalitogenic T cells and formation of neurotoxic reactive oxygen species. | Aktas et al. (2004) |
| Flavonoids | Luteoline scavenges oxygen radicals, inhibits RhoA GTPase and prevents monocyte infiltration into the CNS. | Hendriks et al. (2004) |
| Metallothionein I and II | Antioxidant proteins act anti-inflammatory and neuroprotective. | Espejo et al. (2005) |
| Vitamin D | 1,25-Dihydroxyvitamin D3 declines inducible nitric oxide synthase, chemokines and monocyte recruitment into the CNS and stimulates activated CD4+ T cell apoptosis in the CNS. | Pedersen et al. (2007) |
| K+-channel blocker | Alkoxypsoralens, kaliotoxin, charybdotoxin, psora-4, bupivacaine, anandamide, spermine and ruthenium red inhibit T cell activation. | Beeton et al. (2001), Meuth et al. (2008), Strauss et al. (2000), Wulff et al. (2009) |
| Na+-channel blocker | Phenytoin, flecainide and lamotrigine prevent axonal degeneration. | Bechtold et al. (2004), Bechtold et al. (2006), Lo et al. (2003) |
| Dopamine receptor antagonists | DRD1 antagonist SCH23390 blocks dopamine receptors on Th17 cells. | Nakano et al. (2008) |
| Glutamate receptor antagonists | AMPA/kainate antagonists NBQX and MPQX prevent glutamate-mediated demyelination and neuronal death. | Smith et al. (2000) |
| Histamine receptor antagonists | Histamine-1 receptor antagonist hydroxyzine blocks mast cell degranulation. | Dimitriadou et al. (2000) |
| Serotonin reuptake inhibitors | Venlafaxine suppresses pro-inflammatory cytokines. | Vollmar et al. (2008) |
| Bifunctional hybrid molecules | ||
| Bifunctional peptide inhibitor (BPI) | Hybrid peptides made of integrin CD11a237–246 and antigenic epitopes PLP139–151 or glutamic acid decarboxylase GAD208–217 block the immunologic synapse. | Kobayashi et al. (2008) |
| Fulleren hybrid molecule (ABS-75) | Hybrid molecules made of an antioxidant carboxy-fullerene moiety and NMDA receptor-targeting adamantyl groups inhibit oxidative injury, chemokine expression, CD11b+ cell infiltration, demyelination and axonal loss. | Basso et al. (2008) |
The table is reproduced from Mix et al. (2008) with slight modification with permission of the publisher (Springer).