BackgroundChaperonin 10 (Cpn10) is a mitochondrial molecule involved in protein folding. The aim of this study was to determine the safety profile of Cpn10 in patients with multiple sclerosis (MS).MethodsA total of 50 patients with relapse-remitting or secondary progressive MS were intravenously administered 5 mg or 10 mg of Cpn10 weekly for 12 weeks in a double-blind, randomized, placebo controlled, phase II trial. Clinical reviews, including Expanded Disability Status Scale and magnetic resonance imaging (MRI) with Gadolinium, were undertaken every 4 weeks. Stimulation of patient peripheral blood mononuclear cells with lipopolysaccharide ex vivo was used to measure the in vivo activity of Cpn10.ResultsNo significant differences in the frequency of adverse events were seen between treatment and placebo arms. Leukocytes from both groups of Cpn10-treated patients produced significantly lower levels of critical proinflammatory cytokines. A trend toward improvement in new Gadolinium-enhancing lesions on MRI was observed, but this difference was not statistically significant. No differences in clinical outcome measures were seen.ConclusionsCpn10 is safe and well tolerated when administered to patients with MS for 3 months, however, a further extended phase II study primarily focused on efficacy is warranted.

The 2005 revision of the McDonald diagnostic criteria for multiple sclerosis is reviewed. A standard clinical approach to the diagnosis of multiple sclerosis, including the use of a standard MRI protocol, VEP, CSF evaluation and other paraclinical tests is suggested.

Three recently published randomized controlled studies on the effects of calcium and vitamin D on fracture risk from the UK and the USA were critically reviewed. We found problems related to their external validity compromising their transferability to Denmark. Furthermore, study power was limited because of the selection of low-risk patients, problems with compliance and persistence, and supplementation with calcium and vitamin D outside the protocol. Two recent meta-analyses including the three studies supported the continuous use of calcium and vitamin D to prevent fractures in the elderly.

BACKGROUND: Vitamin D(3) may have therapeutic potential in several diseases, including multiple sclerosis. High doses of vitamin D(3) may be required for therapeutic efficacy, and yet tolerability-in the present context, defined as the serum concentration of 25-hydroxyvitamin D [25(OH)D] that does not cause hypercalcemia-remains poorly characterized. OBJECTIVE: The objective of the study was to characterize the calcemic response to specific serum 25(OH)D concentrations. DESIGN: In a 28-wk protocol, 12 patients in an active phase of multiple sclerosis were given 1200 mg elemental Ca/d along with progressively increasing doses of vitamin D(3): from 700 to 7000 mug/wk (from 28 000 to 280 000 IU/wk). RESULTS: Mean (+/- SD) serum concentrations of 25(OH)D initially were 78 +/- 35 nmol/L and rose to 386 +/- 157 nmol/L (P < 0.001). Serum calcium concentrations and the urinary ratio of calcium to creatinine neither increased in mean values nor exceeded reference values for any participant (2.1-2.6 mmol/L and <1.0, respectively). Liver enzymes, serum creatinine, electrolytes, serum protein, and parathyroid hormone did not change according to Bonferroni repeated-measures statistics, although parathyroid hormone did decline significantly according to the paired t test. Disease progression and activity were not affected, but the number of gadolinium-enhancing lesions per patient (assessed with a nuclear magnetic brain scan) decreased from the initial mean of 1.75 to the end-of-study mean of 0.83 (P = 0.03). CONCLUSIONS: Patients' serum 25(OH)D concentrations reached twice the top of the physiologic range without eliciting hypercalcemia or hypercalciuria. The data support the feasibility of pharmacologic doses of vitamin D(3) for clinical research, and they provide objective evidence that vitamin D intake beyond the current upper limit is safe by a large margin.

BACKGROUND: Past sun exposure and vitamin D3 supplementation have been associated with a reduced risk of multiple sclerosis (MS). There are no previous longitudinal studies of vitamin D in MS. OBJECTIVES: To compare regulation of vitamin D and calcium homeostasis between MS patients and healthy controls. To study correlation of parameters of vitamin D metabolism with MS activity. METHODS: We measured 25-hydroxyvitamin D, intact PTH, calcium, phosphate, magnesium, chloride, alkaline phosphatase, albumin and TSH in serum every three months and at the time of relapses during one year in 23 MS patients and in 23 healthy controls. MRI BOD and T2 activity was assessed every 6 months. RESULTS: Vitamin D deficiency [S-25(OH)D </= 37 nmol/L] was common affecting half of the patients and controls at some time of the year. Seasonal variation of 25(OH)D was similar in the patients and in the controls, but the 25(OH)D serum levels were lower and the iPTH serum levels were higher during MS relapses than in remission. All 21 relapses during the study occurred at serum iPTH > 20 ng/L (2.2 pmol/L), whereas 38% of patients in remission had iPTH </= 20 ng/L. MS patients had a relative hypocalcaemia and a blunted PTH response in the winter. There was no correlation between serum 25(OH)D and MRI parameters. CONCLUSIONS: The endocrine circuitry regulating serum calcium may be altered in MS. There is an inverse relationship between serum vitamin D level and MS clinical activity. The role of vitamin D in MS must be explored further.