US patent application : 20020016313
Vitamin D is a recent arrival in the roster of agents that are known to regulate the immune system. Vitamin D is converted in a two-step process to the hormone, 1,25-dihydroxycholecalciferol (1,25-(OH).sub.2D.sub.3).sup.1 that is a key factor in regulating serum calcium, phosphorus and bone (DeLuca, 1997). This hormone acts in a steroid hormone-like mechanism through a nuclear receptor, the vitamin D receptor (VDR), which is a member of the steroid hormone receptor superfamily (Pike, 1991; Ross, et al., 1993). The discovery of VDR in peripheral blood lymphocytes (Bhalla, et al., 1983; Provvedini, et al., 1983) is a factor that led to the realization that 1,25-(OH).sub.2D.sub.3 is a significant regulator of the immune system. The most striking evidence of a role for 1,25-(OH).sub.2D.sub.3 as an immune system regulator comes from in vivo experiments. 1,25-(OH).sub.2D.sub.3 can prevent the development of EAE (Cantorna, et al., 1996 and U.S. Pat. No. 5,716,946; Lemire and Archer, 1991), experimental arthritis (Cantorna, et al., 1998a), and 1,25-(OH).sub.2D.sub.3 can markedly inhibit transplant rejection (Bouillon, et al., 1995; Hullett, et al., 1998).
EAE is mediated by CD4+ T cells, which mount an inappropriate immune-mediated attack on the central nervous system (CNS). Type-1 helper (Th1) cells specific for CNS antigens induce the disease and the Th1 cytokines interferon (IFN)-y and tumor necrosis factor (TNF)-.alpha. are associated with EAE in mice (Holda and Swanborg, 1982; Powell, et al., 1990). Conversely, type-2 helper (Th2) cells and other cell types which produce interleukin (IL)-4 and transforming growth factor (TGF)-.beta.1 in response to CNS antigens are known to ameliorate EAE. In vivo 1,25-(OH).sub.2D.sub.3 treatments result in a net loss in the total number of lymphocytes and a net increase in the expression of IL-4 and TGF-.beta.1 (Cantorna, et al., 1998b). Conversely the in vivo 1,25- treatments had no effect on IFN-.gamma. or TNF-.alpha. expression (Cantorna, et al., 1998b). The role, if any, for calcium in the regulation of the immune response remains unclear.
The present invention is a method of more effectively treating multiple sclerosis patients. The method comprises the step of administration of an amount of calcium that renders a vitamin D compound effective in preventing or markedly reducing MS symptoms. Preferably, this amount of calcium is 0.5-2 g per patient per day. Most preferably, the amount is between 1 and 2 g of calcium as a salt with a variety of anions, e.g. Co.sub.B.sup.=, PO.sub.4.sup.=, Cl.sub.2.sup.- acetate, gluconate, citrate, etc.