RedSonja wrote:Is chelation back in fashion? haven't seen it for years:
http://www.healthwatcher.net/Quackerywa ... index.html
I still think MS must be some form of auto immune just because treatments like Revimmune or Cytoxan couldn't work if it wasn't.
This paper presents a hypothetical model of role for iron in the development of venous leg ulcers and multiple sclerosis. Elevated concentrations of iron were found in the skin affected by venous hypertension and also in the areas of brain with multiple sclerosis lesions. Individuals with hemochromatosis gene (HFE) mutations: C282Y and H63D, which result in a less efficient transport of iron by macrophages, are characterized by an increased risk for venous leg ulcer and multiple sclerosis. Multiple sclerosis is a T cell-mediated disease, and T cells probably participate in the development of venous ulcers. This deleterious role of ferric ions could be related to the regulation of T cell proliferation and apoptosis. Under normal conditions excessive accumulation of T cells cannot take place, because nitric oxide and interferon-gamma drive these cells toward apoptosis. However, in tissues with a high concentration of iron, T lymphocytes proliferate instead of undergoing apoptosis. This is possible due to the internalization of the INF-gammaR2 chain of the interferon-gamma receptor, the downregulation of inducible nitric oxide synthase expression in macrophages and the inactivation of the active site of caspases. Yet, it should be emphasized that this hypothesis does not claim for the increased concentration of iron as a direct causal factor for the development of venous ulcerations or multiple sclerosis, but rather, iron is a factor that modulates and exaggerates the autoimmune process. Iron chelators, administered systemically or locally, should potentially exhibit therapeutic and prophylactic activity against venous leg ulcers and multiple sclerosis.
Although investigations on the role of iron in MS are
still few, some evidence supports a pivotal role for iron in
MS inflammation. The effect of manipulation of iron level
was investigated in EAE, a form of induced autoimmune
encephalomyelitis in mice used as an experimental model of
MS.31 The incidence of EAE was 60–70% in mice with a
normal iron level and in iron-overloaded mice, but 0% in
iron-deficient mice. The findings suggest that iron
deficiency provides protection from the development of
EAE31 and also challenge traditional views on what
constitutes a normal level of stored iron.14 The authors31
noted that, ‘The failure of iron-deficient mice to develop
EAE is impressive. Many of the pharmaceutical approaches
to inhibiting EAE are less effective than iron deficiency.’
Another group32 investigated the serum concentration
of soluble transferrin receptor (sTFR) in a group of MS
patients. The levels were found to be significantly higher in
patients with active MS, either in progressive or relapsingremitting
clinical form, than in controls. Serum ferritin
levels were also significantly elevated in patients affected by
the active and progressive form.32 Both findings support the
hypothesis above described, which proposes local iron
overload as the initial signal of the inflammatory chain in MS.
There is a relatively small body of literature regarding the effect of iron chelation therapy in MS. Trials of DES and dexrazoxane, a chelator similar to DES, have been completed in animals. Rats with EAE treated with DES before symptom development experienced total symptom suppression, while rats treated after symptom manifestation had a rapid marked attenuation of symptoms.117 A study with a myelin basic protein induced rat EAE model failed to show a treatment effect when DES was administered in the preclinical stage.118 Postulating that DES scavenges and prevents free radical formation and consequently will only be efficacious during active disease, Pedchenko et al.119 treated rats in the active stage of EAE and observed significantly reduced clinical signs when compared to vehicle-treated animals. Dexrazoxane, when injected alone into rats slightly attenuated the course of EAE, while rats given dexrazoxane concomitantly with mitoxantrone experienced improvement on clinical indices when compared with rats treated solely with mitoxantrone.120 This result is of special interest because mitoxantrone carries a significant risk of cardiotoxicity even though it is an effective FDA approved MS therapy while dexrazoxane is known to have cardioprotective effects.121 Only one human trial of iron-related therapy has been performed in human MS (DES in secondary progressive MS); after two years there was no significant improvement in disability score following up to eight courses of DES.25 This lack of treatment effect may potentially be attributed to the advanced disease in the patient population and the small number of the study participants (n=9).
It is evident from the studies presented above that iron deposition occurs in MS and that iron chelation is effective at ameliorating symptoms in animal models. It is unclear, however, the precise role that iron deposition plays in humans and whether chelation therapy or other therapies targeting iron related toxicity can benefit MS patients. Additional studies are warranted to further define the role of iron deposition in MS
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