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Ladymac wrote:We don't have any data that says that BG12 depletes glutathione.

• Fumarates improve multiple sclerosis (MS) and psoriasis, two diseases in which both IL-12 and IL-23 promote pathogenic T helper (Th) cell differentiation. However, both diseases show opposing responses to most established therapies. First, we show in humans that fumarate treatment induces IL-4-producing Th2 cells in vivo and generates type II dendritic cells (DCs) that produce IL-10 instead of IL-12 and IL-23. In mice, fumarates also generate type II DCs that induce IL-4-producing Th2 cells in vitro and in vivo and protect mice from experimental autoimmune encephalomyelitis. Type II DCs result from fumarate-induced glutathione (GSH) depletion, followed by increased hemoxygenase-1 (HO-1) expression and impaired STAT1 phosphorylation. Induced HO-1 is cleaved, whereupon the N-terminal fragment of HO-1 translocates into the nucleus and interacts with AP-1 and NF-κB sites of the IL-23p19 promoter. This interaction prevents IL-23p19 transcription without affecting IL-12p35, whereas STAT1 inactivation prevents IL-12p35 transcription without affecting IL-23p19. As a consequence, GSH depletion by small molecules such as fumarates induces type II DCs in mice and in humans that ameliorate inflammatory autoimmune diseases. This therapeutic approach improves Th1- and Th17-mediated autoimmune diseases such as psoriasis and MS by interfering with IL-12 and IL-23 production.

Anonymoose wrote:Ladymac,
Upon further investigation, it seems the glutathione depletion is just one phase of bg12's (which is dmf) action. It depletes intracellular gsh causing an anti-inflammatory reaction and then it increases it. http://www.nature.com/jid/journal/v127/ ... 0686a.html.

There are also papers describing dmf induced increase and recycling of intercellular gsh. Interesting.

So, you are right. There isn't evidence out there that absolutely proves bg12 depletes gsh chronically. Given the reactions you and others have had, I would still not scratch gsh depletion off the list of suspects. There has to be a simple blood test for gsh levels, doesn't there?

Be well

NHE wrote:

Ladymac wrote:We don't have any data that says that BG12 depletes glutathione.

How about this...

Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells.
J Exp Med. 2011 Oct 24;208(11):2291-303. Epub 2011 Oct 10.

• Fumarates improve multiple sclerosis (MS) and psoriasis, two diseases in which both IL-12 and IL-23 promote pathogenic T helper (Th) cell differentiation. However, both diseases show opposing responses to most established therapies. First, we show in humans that fumarate treatment induces IL-4-producing Th2 cells in vivo and generates type II dendritic cells (DCs) that produce IL-10 instead of IL-12 and IL-23. In mice, fumarates also generate type II DCs that induce IL-4-producing Th2 cells in vitro and in vivo and protect mice from experimental autoimmune encephalomyelitis. Type II DCs result from fumarate-induced glutathione (GSH) depletion, followed by increased hemoxygenase-1 (HO-1) expression and impaired STAT1 phosphorylation. Induced HO-1 is cleaved, whereupon the N-terminal fragment of HO-1 translocates into the nucleus and interacts with AP-1 and NF-κB sites of the IL-23p19 promoter. This interaction prevents IL-23p19 transcription without affecting IL-12p35, whereas STAT1 inactivation prevents IL-12p35 transcription without affecting IL-23p19. As a consequence, GSH depletion by small molecules such as fumarates induces type II DCs in mice and in humans that ameliorate inflammatory autoimmune diseases. This therapeutic approach improves Th1- and Th17-mediated autoimmune diseases such as psoriasis and MS by interfering with IL-12 and IL-23 production.

xpsychiatricmd wrote:From what I remember, a Hemolytic anemia can cause fever. I recently had my CBC which was WNL. Your doctor should give you more information or send you to a Hematologist. Since is a new medication, all side effects/unexpected reactions should be looked at carefully. Good luck.

Tassle24 wrote:Hello. I started Tec about 3 months ago and my last blood results showed anemia - low RBC. Also showed high MPV and low platelets so my neurologist told me to have my primary run more specific tests targeting a potential "hemolytic event," (Coombs direct, retikulocytes, haptoglobin) but those all came back normal. Not sure if it's related, but I also had a normal hepatic (liver) panel except for isolated elevation in direct bilirubin, which my neurologist thought was probably related to blood issues. He was going to follow-up with Biogen but I haven't heard back. So you're not alone, but I have no real answers or insight at this point. My neurologist did say he would not expect Tec to affect RBC.

Reversible leucopenia, lymphopenia and transient eosinophilia are also frequently observed [2]. Leucopenia occurs in a quarter of patients [8,29]. A reduction in lymphocyte count occurs in around 70% of patients [6,8,25,29] and can exceed 50% in about 10% of patients [4]. The dose of Fumaderm® should be reduced if lymphocytes fall below 0.5x109/L or leucocytes fall below 3.0x109/L; if blood counts improve, treatment can continue at the reduced dose, but otherwise Fumaderm® should be stopped [9]. It has been reported that patients with lymphopenia are significantly more likely to show improvement in psoriasis than those whose lymphocyte count stays within the normal range [6,22,24]. Eosinophilia occurring between the fourth and tenth week of treatment [28], in up to a third of patients, generally lasts for one to two months and resolves without intervention [6-8,14,17,22-24,29]. The clinical significance of these changes is not known but long-term follow-up of patients with haematological abnormalities does not suggest they are at an increased risk of infection or cancer [22,29].