Multiple sclerosis evaluation

Schreiber K, Otura AB, Ryder LP, Madsen HO, Jorgensen OS, Svejgaard A, Sorensen PS (2002) Disease severity in Danish multiple sclerosis patients evaluated by MRI and three genetic... 

There have been a number of studies to evaluate the therapeutic effect of carmabinoids against spastic disorders, including multiple sclerosis and spinal cord injury. For example, a randomised placebo-controlled trial in more than... 

A group from La Jolla Pharmaceuticals has released data on their novel hydrazines in recent scientific [20,59,60] and patent literature [61,62], A series of arylallyl hydrazines (e.g., 8 and 9) were shown to be potent, irreversible inhibitors of rat and human SSAO/VAP-1 [59]. LJP-1207 (8, IC50 = 2nM, human) was evaluated in a series of in vivo inflammation models. Significant efficacy was observed in a mouse ulcerative colitis, mouse LPS-induced septic shock, and the rat carrageenan foot models [20], in a mouse model that resembles human multiple sclerosis [63], and in a transient forebrain ischemia model in estrogen-treated ovariectomized female rats [60]. 

Benefit in chronic progressive multiple sclerosis has not been evaluated... 

Assessing the effectiveness of a new drug candidate can be complex and often difficult. This is because some diseases or symptoms do not follow a predictable path. For example, acute conditions such as influenza or insomnia may resolve without intervention, while chronic conditions such as multiple sclerosis or arthritis follow a varying course of progression. Depending on age, treatment, and other risk factors, heart attacks and strokes may produce variable mortality rates. Additional difficulty is introduced by subjective evaluation, which can be influenced by the expectations of patients and physicians. Some of these issues can be addressed in controlled clinical trials. 

B. Indications and nse Avonex is indicated for the treatment of relapsing forms of multiple sclerosis to slow the accumulation of physical disability and decrease the frequency of clinical exacerbations. Safety and efficacy in patients with chronic progressive multiple sclerosis have not been evaluated. 

B. Indications and nse Betaseron is indicated for use in ambulatory patients with relapsing-remitting multiple sclerosis to reduce the frequency of chnical exacerbations. The safety and efficacy of Betaseron in chronic-progressive MS has not been fully evaluated. 

Pharmacokinetics The pharmacokinetics of interferon beta-la (Rebif) in patients with multiple sclerosis have not been evaluated. In healthy subjects, a single injection resulted in a peak serum concentration at about 16 hours after administration. The mean serum elimination half-life was 69 hours but varied widely. Following every-other-day subcutaneous injections, an increase in the area under the serum concentration versus time curve (AUC) of approximately 240% was observed. Clearance has been estimated at 33 to 55 liters/h. 

E. Therapeutic response Two studies evaluated the safety and efficacy of Rebif in patients with relapsing-remitting multiple sclerosis. Study 1 was a placebo-controlled, 2-year trial in 560 patients with multiple sclerosis for at least 1 year. The primary efficacy end point was the number of clinical exacerbations. The mean numbers of exacerbations per patient over 2 years was 1.82 and 1.73 in those who received either 22 pg or 44 pg three times per week compared with a mean number of 2.56 in those who received placebo. The decrease in the number of exacerbations in the Rebif groups compared with the placebo group was statistical significant, but the difference between... 

Compounds of type 107 were evaluated as MMP inhibitors <1999JME4547>. MMPs are a structurally related class of enzymes that is responsible for the metabolism of the extracellular matrix proteins and are linked to diseases such as arthritis and multiple sclerosis. 

The intramuscular injection of naked pDNA has also been evaluated for therapy of EAE, a mouse model of multiple sclerosis. The disease is induced in mice by s.c. injection of myelin basic protein (MBP) or proteolipid protein (PLP). In a recent study, mice were injected i.m. with pDNA encoding either IL-4/IgG or TGF / 48 hours prior to each MBP injection (on days zero and seven) (Piccirillo and Prud -homme, 1999). The disease severity was 70% lower in the IL-4/IgG or TGF / -treated mice and the mean clinical scores were significantly reduced in both groups. In addition, the IL-4 and TGF -treated mice had significantly reduced CNS inflammation, reduced T cell proliferative responses to MBP and low levels of the Th 1 cytokines IL-12 and IFN7. Thus, the pDNA therapy appeared to shift the mice to a Th2 response, which was therapeutic and reduced the severity of the disease. 

Karussis DM, et al. (1996) Treatment of secondary progressive multiple sclerosis with the immunomodulator linomide a double-blind, placebo-controlled pilot study with monthly magnetic resonance imaging evaluation. Neurology 47(2) 341-346... 

In a randomized, double-blind, placebo-controlled, crossover trial the effect of the synthetic delta-9-tetrahy-drocannabinol dronabinol on central neuropathic pain was evaluated in 24 patients with multiple sclerosis (58). Oral dronabinol reduced central pain. Adverse events were reported by 96% of the patients compared with 46% during placebo treatment. They were more common during the first week of treatment. The most common adverse events during dronabinol treatment were dizziness (58%), tiredness (42%), headache (25%), myalgia (25%), and muscle weakness (13%). There was increased tolerance to the adverse effects over the course of treatment and with dosage adjustments. 

The Multiple Sclerosis Functional Composite (MSFC) was developed by the MS Consortium (Whitaker et al., 1995) for evaluating disabilities ranging from motor function to cognitive changes and to replace the EDSS. The three tools included in the MSFC are a timed 25 foot walk, the 9-hole peg test for hand dexterity and the Paced Auditory Serial Addition Test (PASAT). The MSFC is a quandfiable measure of disability but ten years later, it is sdll infrequently incorporated as a primary outcome measure because of the increased time element necessary to validate the individual tests and the dme necessary for their adminisd adon. 

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