How Miraxion Might Work

HD Lighthouse Contributing Editor's Comment: While the HD community waits for the results of the Phase III clinical trial of Miraxion, it is worthwhile to review the evidence to date and discuss how it may affect Huntington's Disease pathology in light of what we already know.

The Lighthouse has been following this ultra pure ethyl-EPA compound for years now. A previous Phase III clinical trial ended inconclusively. There was a trend towards stable or improved motor function in the those patients who followed the treatment protocol but statistical significance was not achieved for the intent-to-treat group vs. the placebo group. Another finding was that Miraxion seemed to be most effective in those with CAG repeats of less than 45. See http://hdlighthouse.org/research/drugs-supps/updates/1180miraxion.php These promising results led Amarin to institute two additional Phase III clinical trial, one in the USA and one in Europe.

A recently published study by Amarin researchers discusses the possible mechanisms by which Miraxion might work based on past preclinical and clinical research with Miraxion and on the basic research which has advanced our knowledge of disease pathology.

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There are two important things to note about the latest clinical trials. Assuming there are good results and Miraxion is approved by the FDA, the HD community will not have to worry about being denied this compound based on a CAG score. The trial was designed to reflect the HD patient community's CAG distribution with more counts in the low 40s but did not exclude people with higher counts. That means that the results will 'apply' to everyone.

Second, the trials were designed to test Miraxion as a compound which addresses symptoms rather than the disease pathology itself. Until we have biomarkers which are approved as surrogates for the current clinical assessment of the disease procession, clinical trials take too long and cost too much. We need to get treatments to people now. If Miraxion is shown to be a safe and effective drug to improve motor scores, let's get it to market for that reason alone and make our own judgments based on all the available evidence as to whether it affects the disease process.

Watch this space. The latest trials were completed in February. The results are currently being analyzed and will be made available in May, first to research participants and then to the Lighthouse immediately afterwards. We will report the results as soon as we can get them up on the site.

-- Marsha L. Miller, Ph.D.
Posted to the HDL: 03-19-2007

Ethyl-EPA in Huntington disease-Potentially relevant mechanism of action

Harald Murck and Mehar Manku

The pathomechanisms involved in the neuronal dysfunction in Huntington disease (HD) are still unresolved and may be heterogeneous. One potential mechanism might be related to the induction of mitochondrial dysfunction in the CNS. This might lead firstly to neuronal dysfunction and finally to the activation of apoptotic pathways. Several compounds, which should alleviate mitochondrial dysfunction, have been tested in preclinical models as well as in clinical trials of different scale. Recently we reported the efficacy of Ethyl-eicosapentaenoic acid (Ethyl-EPA) in patients with HD. Ethyl-EPA is a polyunsaturated fatty acid from the n-3 group, which is in clinical development for HD and melancholic depression. In our trial with Ethyl-EPA in HD responding patients could be characterized by either a lower CAG repeat number or a chorea-predominant clinical expression of the disease. Here we would like to describe some evidence on the potential mechanism of action of Ethyl-EPA in HD. We specifically focus on pathways, which are known to be influenced in HD and are modified by Ethyl-EPA and which points to an involvement of mitochondrial function as a common target. Some attention is given to the NF-kappa B pathway and the c-Jun amino-terminal kinases (JNK) pathway, which both may lead to an activation of the antiproliferative factor p53 and consequently mitochondrial dysfunction. Further the effects of EPA or Ethyl-EPA in preclinical models of HD are described. The evidence from these studies led to the design of phase III clinical trials, which are ongoing.

Source: Brain Research Bulletin 2007 Apr 30;72(2-3):159-64. Epub 2006 Nov 15.