TMJ 'dysfunction' - Health implications

The Fungicide Dimethyl Fumarate (CAS 624-49-7)
Back in February 2008 the UK consumer programme “Watchdog” reported a story about Chinese manufactured leather sofas, sold by a number of leading high street retailers in the UK, including Argos, Land of Leather and Walmsleys, that had lead to severe skin reactions due to the use of Dimethyl Fumarate.
The fungicide was contained within a sachet which was placed inside the sofas in order to protect against mould during storage, transit and everyday usage.
These sachets often look similar to those that contain silica gel, a non harmful desiccant frequently used in leather products.

By early 2009, more than 5,000 people in the UK had reported skin, chest and eye injuries after using imported furniture.

On 1 May 2009 the European Commission banned products containing “DMF” from being placed on the market. Any products already on the market had to be either withdrawn or recalled from customers.
DMF has been found to be an allergic sensitiser at low concentration and can produce extensive and pronounced eczema that is difficult to treat. Concentrations as low as one part per million may produce allergic reactions.

In Finland, from 2006 to 2007, an allergic reaction to the substance resulted in 60 users receiving serious rashes.

In Spain, around 40 brands of footwear have been found to contain DMF which is often used while the shoes are in storage.

A popular French distribution chain also found footwear sold in its stores to have been contaminated by DMF and had received complaints of skin damage.

During 2009 there had been product recalls in Spain, France, Poland, Finland, Sweden the UK and Germany.

Health problems include skin irritation, burns and, in some cases, acute respiratory difficulties.

While DMF maybe an effective antifungal agent, it is harmful in contact with the skin and if in contact with the eyes could result in serious damage.

MSers please note that this antifungal is soon to be introduced as a DMD for $50,000 per patient per year!

UPDATE:
http://www.fiercebiotech.com/story/teva ... 2013-01-10

http://www.pharmatimes.com/Article/13-0 ... _pill.aspx

"The citation: "Kidney changes were observed after repeated oral administration of dimethyl fumarate in mice, rats, dogs, and monkeys. Renal tubule epithelia regeneration, suggestive of tubule epithelial injury, was observed in all species. Renal tubular hyperplasia was observed in rats with life time dosing (2 year study). Cortical atrophy was observed in dogs and monkeys, and in monkeys, single cell necrosis and interstitial fibroses were observed in animals that received daily oral doses of dimethyl fumarate for 12 months at six times the RHD based on AUC."

Read more: Teva tries to slow arrival of Biogen's competing MS blockbuster - FierceBiotech http://www.fiercebiotech.com/story/teva ... z2HkOcaPZi
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FURTHER UPDATE: January 14, 2013

In response to the queries regarding BG12, fumarates and PML. Yes, there have been 5 cases of PML in people on Fumaderm for psoriasis. One of these cases has been presented at an academic meeting in Germany and the abstract is presented below the other 4 cases that have been reported via the German Adverse Drug Reaction Database.

Ermis et al. Fumaric acid-associated progressive multifocal leukencephalopathy (PML), treatment and survival in a patient with psoriasis. Kongress der Deutschen Gesellschaft für Neurologie mit Fortbildungsakademie28.09.2011 - 01.10.2011.

Background: Fumaric acid and/or its derivates were found to be effective and safe in the treatment of psoriasis vulgaris. In addition, treatment with fumaric acid is currently evaluated in phase II/III trials for the therapy of multiple sclerosis. PML is a rare but frequently fatal disease caused by the uncontrolled replication of JC virus (JCV), a polyomavirus, in the brains of some immunocompromised individuals, including 4 to 5% of HIV-positive patients with AIDS, also occurring in association with leukemia and lymphoma.

Clinical case: They describe a 74-year-old male with psoriasis who developed subacute neurologic symptoms after 3 years of monotherapy with fumaric acid. The patient had a history of psoriasis for more than 5 years and he was treated with different immunosuppressive and immunomodulatory therapies including corticosteroids, a second generation retinoid, and methotrexate.

Results: MRI scan demonstrated a subcortical area of T2-hyperintensity within the white matter of the left temporal lobe, without gadolinium enhancement. PML was confirmed by brain biopsy and positive JC virus-PCR in the brain biopsy and cerebrospinal fluid (CSF). Discontinuation of fumaric acid resulted in an induction of an immune reconstitution inflammatory syndrome (IRIS) with gadolinium enhancement after five weeks. The patient was treated with mefloquine and mirtazapine. At 5 months there was improvement of neurological symptoms, regression of MRI lesions and JC virus load in the CSF was below detection limit.

Conclusions: This is the first report of PML associated with the small molecule fumaric acid, a therapy that in contrast to other modern immune therapies that may cause PML like rituximab, natalizumab, efalizumab, and infliximab does not belong to the group of monoclonal antibodies. JC virus associated PML occurs in patients with an immunosuppressive syndrome, e.g. lymphoma or HIV infection and in most cases inevitably leads to death of the patients. Four patients treated with Efalizumab for psoriasis reportedly developed PML, all of them died within short duration of the disease. Lately several multiple sclerosis patients who had been treated with natalizumab developed a PML and survived the disease after cessation of the immunosuppressive treatment. With this present case, we describe for the first time fumaric acid-associated PML and IRIS in a patient with psoriasis and the successful clinical management.

The following are the summaries of another 4 cases of PML in patients with psoriasis treated with Fumaderm since its launch in Germany in 1993. The extract is from the German BfArM's ADR Database. The case report does not match with any of the four cases reported in BfArM's ADR.

"In addition to this another case developed PML, whilst on another formulation of fumaric acid. This case had lymphopenia, a PML risk factor. If and when we get information on this case we will let you know."

All DMT have Side-Effects

Posted: 13 Jan 2013 04:25 AM PST
In light of the Teva's challenge to Biogen's BG-12, what next? Genzymne's Lemtrada; if we are talking safety?

However, I would like to point out that when you move from low efficacy first-line drugs to much higher-efficacy drugs that globally inhibit immune function, then we should be expecting consequences of this, because this is the biology.

This will include

Increased risk of Cancers
Increased Risk of Infections


This is because, this is what the immune system does. It protects you from infections and the development of tumours. A very troubling infection is caused by JC virus that leads to PML, as we have no drug to deal with it and its consequences can be fatal. So if you keep your immune system low then this is a possibility.

This is a real problem with Tysabri, but has been shown to occur following B cell depletion with rituximab etc. There are reported cases of PML with Fumaderm, which contains the active ingredient in BG-12.
http://multiple-sclerosis-research.blog ... esearch%29