Sclerosis MS

MS is a chronic neurologic disease associated w ith demyelin-ation and death of neuronal axons. Multiple plaques or scares form w ithin the CNS resulting in a w ide range of neurological deficits. Because of the role of demyelination in the disease, it is frequently classified w ith autoimmune disorders. Information on the neuroimmunologic aspects of the various types of MS are covered in a previous chapter. 

Asians, Black Africans, and aboriginal Australians. However, while these particular ethnic groups have an increased incidence of MS, identical twin studies show only a 30% correlation in disease occurrence in individuals sharing the same DNA and environmental factors. Epidemiological genetic studies show a relational rather than a causative effect (Barcellos et al., 2002). While regions of interest have been identified, none have been linked to MS wdth certainty. 

Multi System Involvement w ith Emphasis on Neurologic Syndromes 

The characteristics of MS are covered in previous chapters. In general, MS is a disease of the CNS wdth other systems involved w hen neuronal connections are disrupted. As a result, symptoms vary wddely. Outcome measures and progression are review ed in conjunction wdth chapter 3.1.2 on the therapeutic measures available for treatment of MS. 

Axonal injury may occur not only in the late phases of MS but also after early episodes of inflammatory demyelination (Lucchinetti et al., 1999 Trapp et al., 1998 Bitsch et al., 2000 De Stefano et al., 2001). Gray matter lesions and axonal injury in normal appearing w hite matter are reported in MS implying that axonal injury could trigger demyelination (Tsunoda and Fujinami, 2002). The pathogenesis of this early axonal injury is still unclear. 

Multi System Involvement with Emphasis on Neurologic Syndromes 

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Multiple sclerosis (MS) 4. In rats with EAE, an animal model of multiple sclerosis, AEA and 2-AG levels are decreased in the striatum and midbrain. This might be associated with motor impairment 4. Inhibitors of degradation (both FAAH and cellular re-uptake)... 

Multiple sclerosis (MS) is a complex inflammatory disease of the central nervous system (CNS) that is variable in terms of symptoms and presentation. The name refers to two features of the disease multiple describes the number of CNS lesions and sclerosis refers to the demyelinated lesions. Today, these lesions are usually called plaques, rather than scleroses. Although scientific understanding of MS has progressed at a rapid pace, there are still many areas of evolving knowledge. 

Rheumatoid arthritis (RA), multiple sclerosis (MS) and systemic lupus erythematosus (SLE)... 

Multiple sclerosis (MS) is a devastating disease of the CNS that produces demyelination and inflammation. It is believed that its pathogenesis involves an immune reaction against various components of the myelin sheath. In a study by Lock et al. (2002), the gene expression patterns of brain lesions obtained during autopsies of MS patients were examined by microarray cluster analysis. A total of 1080 genes (from 7026 represented... 

There is much interest in the medical applications of Cannabis sativa L. (marijuana). An oral spray consisting of the marijuana constituents, cannabidiol (CBD,19) and A -mzw-tetrahydrocannabinol (THC, 20), has been approved recendy in Canada for the treatment of neuropathic pain associated with multiple sclerosis (MS), and it is possible that this drug will be approved elsewhere in the near future. ... 

Nervous system Acute exacerbations of multiple sclerosis (MS). 

Multiple sclerosis (MS) - For the treatment of relapsing forms of MS to slow the accumulation of physical disability and decrease the frequency of clinical exacerbations. 

Myocardial toxicity, manifested in its most severe form by potentially fatal CHF, may occur either during therapy with mitoxantrone or months to years after termination of therapy. Mitoxantrone use has been associated with cardiotoxicity this risk increases with cumulative dose. In cancer patients, the risk of symptomatic CHF was estimated to be 2.6% for patients receiving up to a cumulative dose of 140 mg/m. For this reason, monitor patients for evidence of cardiac toxicity and question them about symptoms of heart failure prior to initiation of treatment. Monitor patients with multiple sclerosis (MS) who reach a cumulative dose of 100 mg/m for evidence of cardiac toxicity prior to each subsequent dose. Ordinarily, patients with MS should not receive a cumulative dose greater than 140 mg/m. Active or dormant cardiovascular disease, prior or concomitant radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, or concomitant use of other cardiotoxic drugs may increase the risk of cardiac toxicity. Cardiac toxicity with mitoxantrone may occur at lower cumulative doses whether or not cardiac risk factors are present (see Warnings and Administration.and.Dosage). 

Multiple sclerosis (MS) is the most frequent inflammatory demyeli-nating disease of the central nervous system that affects worldwide about 2.5 million people with no cure. Myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-induced EAE) in DA rats is an appropriate model for therapeutic testing, sharing many features with human multiple sclerosis. 

Bladder dysfunction. Two whole-plant extracts of Cannabis sativa were administered to patients with advanced multiple sclerosis (MS) and refractory troublesome lower urinary tract symptoms. The patients... 

Mechanism of Action An immunosuppressive whose exact mechanism is unknown. May act by modifying immune processes thought to be responsible for the pathogenesis of mulfiple sclerosis (MS). Therapeutic Effect Slows progression of MS. Pharmacokinetics Substantial fraction of glatiramer is hydrolyzed locally. Some fraction of injected material enters lymphatic circulation, reaching regional lymph nodes some may enter systemic circulation intact. 

Recent development highlighted a shift in FDA position and interpretation of the market exclusivity clause. Under the orphan designation, three interferon products, Betaseron (IFN-pib), Avonex (IFN-pia) and Rebif (IFN-pia) are currently approved for treatment of multiple sclerosis (MS). The interplay in drug safety and efficacy consideration, business strategies, and regulatory rationale permitting approval of the three drugs for MS treatment is discussed in Box 3.5. 

A recombinant IFN-P, IFN-pia (Rebif Serono and Avonex Biogen) is produced for commercial use in Chinese hamster ovary (CHO) cells. A synthetic mutant produced in bacteria has a substitution of serine for cysteine at amino acid 17, yielding IFN-pib Betaseron Berlex). Both IFN-pia and IFN-pib are approved by the FDA for treatment of multiple sclerosis (MS) and have shown comparable biological activity (see Section 7.3). In vivo IFN-a2 and IFN-alb show comparable biological activity as well as similar side effects [54,55]. However, IFN-P is eliminated faster, resulting in no detectable serum peak levels [56]. The clinical consequence of this is not known. Objective responses, whether partial or complete tumor regression, have been documented in patients with carcinoma of the breast, hairy-cell leukemia, and non-small-cell lung cancer [57,58]. 

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS), affecting... 

Indications Treatment of relapsing-remitting forms of multiple sclerosis (MS) to slow the accumulation of physical dis-... 

E Role in therapy Betaseron is useful for reducing symptomatic exacerbation in multiple sclerosis (MS) patients with relapsing-remitting disease. The drug should be considered in patients with ch-nically deflnite or laboratory-supported definite disease. It is not indicated in those patients with primary progressive MS. Interferon beta-la (Avonex) has also demonstrated activity in MS patients. 

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