Endogenous neuroprotection in multiple sclerosis.

Endogenous neuroprotection was mostly investigated in stroke, trauma and neurodegenerative diseases. However, several endogenous neuroprotective mechanisms have been identified recently in multiple sclerosis: protective autoimmunity, direct low molecular weight antioxidants, indirect antioxidants inducing cytoprotective proteins, kynurenine pathways, ischemic preconditioning, integrated cell response, cannabinoids and complement system. Numerous endogenous neuroprotective strategies are investigated in animal models but the translation into the clinic of positive results obtained in the laboratory has been disappointing so far Endogenous neuroprotection is the net result of complex and interconnected mechanisms and modulating an individual neuroprotective pathway will likely yield a partial benefit, if any.

Boosting endogenous neuroprotection in multiple sclerosis: the ASsociation of Inosine and Interferon beta in relapsing- remitting Multiple Sclerosis (ASIIMS) trial.

Anti-inflammatory drugs are effective on relapses, but neuroprotective agents to prevent disability are still unavailable. Uric acid has neuroprotective effects in experimental models including encephalomyelitis and appears to be involved in multiple sclerosis. Oral administration of inosine, a precursor of uric acid, increases serum uric acid levels and is well tolerated.

Neurodegeneration in multiple sclerosis: the role of oxidative stress and excitotoxicity.

In multiple sclerosis (MS) disability results from neuronal and axonal loss, the hallmark of neurodegenerative diseases (ND). Neurodegeneration is initiated by microglia activation and mediated by oxidative stress and excitotoxicity. The same sequence of events has been consistently observed in MS.

Oxidative stress and excitotoxicity: a therapeutic issue in multiple sclerosis?

There is increasing evidence that multiple sclerosis (MS) is not only characterized by immune mediated inflammatory reactions but also by neurodegenerative processes. In neurodegenerative diseases, neuronal and axonal loss is mediated by oxidative stress and excitotoxicity which constitute a final common toxic pathway. Importantly, peroxynitrite is the key mediator of those two intertwined pathomechanisms.

Compared benefit of approved and experimental immunosuppressive therapeutic approaches in multiple sclerosis.

An important amount has been learnt about the mechanisms of action, efficacy and long-term toxicities of mitoxantrone. Importantly, recent observations strongly suggest that early administration of potent immunosuppressants (mitoxantrone and alemtuzumab) is definitely more effective than approved immunomodulators to delay or even reverse disability progression. Given the cardiotoxicity of mitoxantrone, restricting exposure to the drug to 2 or 3 years, the benefits and risks of immunosuppressants previously used as off-label treatments (cyclophosphamide and cladribine) have been revisited, and the potential efficacy in multiple sclerosis of recent immunosuppressants used in other autoimmune diseases, organ transplantation and cancer therapy has received increasing attention.

A comparison of the benefits of mitoxantrone and other recent therapeutic approaches in multiple sclerosis.

The approval by the FDA of four immunomodulators (three IFNs and glatiramer acetate) and one immunosuppressant (mitoxantrone; Novantrone) for the treatment of multiple sclerosis is definitely the most important progress in this field since the first description of the disease > 150 years ago. However, both types of immunotherapies raise specific problems. Immunomodulators benefit patients in the relapsing-remitting phase, or patients in the secondary-progressive phase showing clinical and/or radiological signs of active inflammatory processes.

Psychological functioning in primary progressive versus secondary progressive multiple sclerosis.

Psychological functioning in two types of multiple sclerosis (MS) patients is assessed: primary progressive (PP) and secondary progressive (SP) patients. On the basis of differences in clinical course and underlying pathology we hypothesized that primary progressive patients and secondary progressive patients might have different psychological functioning. Seventy patients treated in an MS centre were examined cross-sectionally.

Mitoxantrone immunotherapy in multiple sclerosis.

Mitoxantrone, a cytotoxic agent recently developed, was subsequently found a very potent immunosuppressor. Experimental data in experimental allergic encephaloymyelitis demonstrated a dramatic suppression of both active and passive forms. Immune effects concern cellular and humoral components and are particularly persistent.