Chronic progressive Multiple Sclerosis is refractory to many conventional treatments. We performed a pilot study testing desferoxamine (DFO) as a candidate in the treatment of chronic progressive Multiple Sclerosis. DFO was given daily by 8 h subcutaneous infusions at a dose of 2 grams daily for 7 days, followed by 1 gram daily for 7 days. Eighteen of 19 individuals completed the full dose of 21 grams. One patient was unable to complete the course due to nausea. No acute deterioration of neurological status was seen during the administration of DFO. No worsening of vision or hearing was noted except that the one patient who was unable to tolerate the medication had a transient reduction in hearing. All patients had a local redness at the injection site. None of the patients had any sudden worsening during or shortly after the treatment This pilot study suggests that DFO is relatively well tolerated by Multiple Sclerosis patients when given in a short course of therapy.
1 Raine CS. (1991) Oligodendrocytes and central nervous system myelin. In: Davis RL and Robertson DM (eds). Textbook of Neuropathology, 2nd ed. 1991. Williams and Wilkins: Baltimore, Maryland, pp. 115–140.
2.
2 Nathan CF, Tsunawaki S. (1986) Secretion of toxic oxygen products by macrophages: regulatory cytokines and their effects on the oxidase.1986 Biochemistry of Macrophages. Pitman (Ciba Foundation Symposium 118) pp. 211–230.
3.
3 Halliwell B, Gutteridge JMC. (1986) Oxygen free radicals and iron in relation to biology and medicine: Some problems and concepts. Arch Biochem Biophys246: 501–514.
4.
4 Halliwell B. (1989) Oxidants and the central nervous system: some fundamental questions. Acta Neurol Scand126: 23–33.
5.
5 Siejo BK, Agardh C-D, Bengtsson F. (1989) Free radicals and brain damage. Cerebrovascular Brain Metab Rev1: 165–211.
6.
6 Rajan KS, Colburn RW, Davis JM. (1976) Distribution of metal ions in the subcellular fractions of several rat brain areas. Life Sci18: 423–432.
7.
7 LeVine SM, Macklin WB. (1990) Iron-enriched oligodendrocytes: A reexamination of their spatial distribution. J Neurosci Res26: 508–512.
8.
8 LeVine SM. (1991) Oligodendrocytes and myelin sheaths in normal, quaking and shiverer brains are enriched in iron. J Neurosci Res29: 413–419.
9.
9 Borg DC. (1993) Oxygen free radicals and tissue injury. A Reference outline. In: Tarr M and Samson F eds. Oxygen free radicals in tissue damage.Birkhauser: Boston, pp. 12–52.
10.
10 Borg DC, Schaich KM. (1988) Iron and iron-derived radicals. In: Halliwell B (ed). Oxygen Radicals and Tissue Injury Federation of American Societies for ExperimentalBiology: Bethesda, MD. pp. 20–26.
11.
11 Bowern N, Ramshaw IA, Clark IA, Doherty PC. (1984) Inhibition of autoimmune neuropathological process by treatment with an iron-chelating agent. J Exp Med160: 1532–1543.
12.
12 Willenborg DO, Bowern NA, Danta G, Doherty PC. (1988) Inhibition of allergic encephalomyelitis by the iron chelating agent desferoxamine: differential effect depending on type of sensitizing encephalitogen. J Neuroimmunol17: 127–135.
13.
13 Ikeda Y, Ikeda K, Long DM. (1989) Comparative study of different iron chelating agents in cold-induced brain edema. Neurosurgery24: 821–824.
14.
14 Rao NA et al. (1986) Effect of iron chelation on severity of ocular inflammation in an animal model. Ophthalmology104: 1369–1371.
15.
15 Shatos MA, Doherty JM, March TP, Mossman BT. (1987) Prevention of asbestos-induced cell death in rat lung problasts and alveolar macrophages by scavenger of active oxygen species. Environ Res44: 103–116.
16.
16 Weinberg K. (1990) Novel uses of Deferoxamine. Am J Ped Hem One12: 9–13.
17.
17 Boyce NW, Holdsworth SR. (1986) Treatment of rheumatoid arthritis with desferoxamine. Q J Med61: 1153–1158.
18.
18 Kruck TPA, Fisher EA, McLachlan DRC. (1990) Suppression of deferoxamine mesylate treatment-induced side effects by coadministration of isoniazid in a patient with Alzheimer's disease subject to aluminium removal by ion sepcific chelation. Clin Pharmacol Ther48: 439–446.
19.
19 McLachlan DRC et al. (1991) Intramuscular desferoxamine in patients with Alzheimer's disease. Lancet337: 1304–1308.
20.
20 Goodin DS. (1991) The use of immunosuppressive agents in the treatment of multiple sclerosis; a critical review. Neurology41: 980–985.
21.
21 Friedman JE et al. (1990) A randomized trial of colchicine as placebo in progressive sclerosis. Ann Neurol28: 244.
22.
22 Bentur Y, McGuigan M, Koren G. (1991) Deferoxamine (Desferrioxamine): New toxicities for an old drug. Drug Safety6: 37–46.
23.
23 Olivieri NF et al. (1986) Visual and auditory neurotoxicity in patients receiving subcutaneous desferoxamine infusions. N Engl J Med314: 869–873.
24.
24 Brock JH, Ng J. (1983) The effect of deferoxamine on the growth of Staphylococcus aureus, Yersinia enterocolitica, and Streptococcus Faecalis in human serum; uptake of deferoxamine-bound iron. FEMS Microbiol Lett20: 439–442.
25.
25 Freedman MH, Boyden M, Taylor M, Skarf B. (1988) Neurotoxicity associated with deferoxamine therapy. Toxicology49: 283–290.
26.
26 Kurtzke JF. (1983) Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurology33: 1444–1452.
27.
27 Poser CM et al. (1983) New diagnostic criteria for multiple sclerosis: guidelines for research. Neurology13: 227–231.
28.
28 Halliwell B. (1985) Use of Desferioxamine as a ‘probe’ for iroe-dependent formation of hydroxyl radicals. Evidence for a direct reaction between desferal and the superoxide radical. Biochem Pharm34: 229–233.
29.
29 Davies MJ et al. (1987) Desferrioxamine (Desferal) and superoxide free radical. Biochem J246: 725–729.
30.
30 Morehouse KM, Flitter WD, Maso RP. (1987) The enzymatic oxidation of Desferal to a nitroxide free radical. FEBS Lett222: 246–250.
31.
31 Beckman JS et al. (1990) Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA87: 1620–1624.
32.
32 Radi R, Beckman JS, Bush KM, Freeman BA. (1991) Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys288: 481–487.
33.
33 Dang S, Rasmussen CA, LeVine SM. (1994) Immunocytochemical localization of desferrioxamine in the liver, kidney and brain of developing and adult mice: Implications for drug processing and therapeutic mechanisms. Res Comm Mol Path Pharm86: 43–57.
34.
34 Stohl W, Kaplan MS, Gonatas NK. (1979) A quantitative assay of experimental allergic enchalomyelitis in the rat based on permeability of spinal cords to 1251-human gamma-globulin. J Immunol122: 920–925.
35.
35 Goldmuntz EA, Brosnan CF, Norton WT. (1986) Prazosin treatment suppresses increased vascular permeability in both acute and passively transferred experimental autoimmune encephalomyelitis in the Lewis rat. J Immunol137: 3444–3450.
36.
36 Claudio L, Kress Y, Factor J, Brosnan CF. (1990) Mechanisms of edema formation in experimental autoimmune encephalomyelitis: The contribution of inflammatory cells. Am J Path137: 1033–1045.
37.
37 Norstrand IF, Craelius W. (1989) A trial of Deferoxamine (Desferal) in the treatment of multiple sclerosis: a pilot study. Clinical Trials Journal26: 365–369.
