Abstracts of articles do not tell the full story.
Recently published paper suggests benefit (equal to prednisone). While the abstract sounds wonderful, the article is much less convincing. I suspect this will run through the community, so thought it might be useful to give you a head's up.
Efforts to standardize measurements are underway at major institutions. Studies like this, making major claims, must be repeated and data confirmed (or not), It is essential to repeat this study as it would provide critical information for us as we make informed decisions about what to do or not to do for our boys.
http://www.limbrel.com/limbrel.php
Flavocoxid counteracts muscle necrosis and improves functional properties in mdx mice: a comparison study with methylprednisolone.
Exp Neurol. 2009 Sep 25.
Messina S, Bitto A, Aguennouz M, Mazzeo A, Migliorato A, Polito F, Irrera N, Altavilla D, Vita GL, Russo M, Naro A, De Pasquale MG, Rizzuto E, Musarò A, Squadrito F, Vita G.
Department of Neuroscience, Psychiatry and Anaesthesiology, University of Messina, Messina, Italy.
http://www.ncbi.nlm.nih.gov/pubmed/19786019
Muscle degeneration in dystrophic muscle is exacerbated by the endogenous inflammatory response and increased oxidative stress. A key role in is played by nuclear factor(NF)- kappaB. We showed that NF-kappaB inhibition through compounds with also antioxidant properties has beneficial effects in mdx mice, the murine model of Duchenne muscular dystrophy (DMD), but these drugs are not available for clinical studies. We evaluated whether flavocoxid, a mixed flavonoid extract with anti-inflammatory, antioxidant and NF-kappaB inhibiting properties, has beneficial effects in mdx mice in comparison with methylprednisolone, the gold standard treatment for DMD patients. Five-week old mdx were treated for 5 weeks with flavocoxid, methylprednisolone or vehicle. The evaluation of in vivo and ex vivo functional properties and morphological parameters was performed. Serum samples were assayed for oxidative stress markers, creatine-kinase (CK) and leukotriene B-4 determination. Cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), tumor necrosis factor-alpha, p-38, JNK1 expression was evaluated in muscle by western blot analysis. NF-kappaB binding activity was investigated by electrophoresis mobility shift assay. The administration of flavocoxid: 1) ameliorated functional properties in vivo and ex vivo; 2) reduced CK; 3) reduced the expression of oxidative stress markers and of inflammatory mediators; 4) inhibited NF-small ka, CyrillicB and mitogen-activated protein kinases (MAPKs) signal pathways; 5) reduced muscle necrosis and enhanced regeneration. Our results highlight the detrimental effects of oxidative stress and NF-kappaB, MAPKs and COX/5-LOX pathways in the dystrophic process and show that flavocoxid is more effective in mdx mice than methylprednisolone.
Efforts to standardize measurements are underway at major institutions. Studies like this, making major claims, must be repeated and data confirmed (or not), It is essential to repeat this study as it would provide critical information for us as we make informed decisions about what to do or not to do for our boys.
http://www.limbrel.com/limbrel.php
Flavocoxid counteracts muscle necrosis and improves functional properties in mdx mice: a comparison study with methylprednisolone.
Exp Neurol. 2009 Sep 25.
Messina S, Bitto A, Aguennouz M, Mazzeo A, Migliorato A, Polito F, Irrera N, Altavilla D, Vita GL, Russo M, Naro A, De Pasquale MG, Rizzuto E, Musarò A, Squadrito F, Vita G.
Department of Neuroscience, Psychiatry and Anaesthesiology, University of Messina, Messina, Italy.
http://www.ncbi.nlm.nih.gov/pubmed/19786019
Muscle degeneration in dystrophic muscle is exacerbated by the endogenous inflammatory response and increased oxidative stress. A key role in is played by nuclear factor(NF)- kappaB. We showed that NF-kappaB inhibition through compounds with also antioxidant properties has beneficial effects in mdx mice, the murine model of Duchenne muscular dystrophy (DMD), but these drugs are not available for clinical studies. We evaluated whether flavocoxid, a mixed flavonoid extract with anti-inflammatory, antioxidant and NF-kappaB inhibiting properties, has beneficial effects in mdx mice in comparison with methylprednisolone, the gold standard treatment for DMD patients. Five-week old mdx were treated for 5 weeks with flavocoxid, methylprednisolone or vehicle. The evaluation of in vivo and ex vivo functional properties and morphological parameters was performed. Serum samples were assayed for oxidative stress markers, creatine-kinase (CK) and leukotriene B-4 determination. Cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), tumor necrosis factor-alpha, p-38, JNK1 expression was evaluated in muscle by western blot analysis. NF-kappaB binding activity was investigated by electrophoresis mobility shift assay. The administration of flavocoxid: 1) ameliorated functional properties in vivo and ex vivo; 2) reduced CK; 3) reduced the expression of oxidative stress markers and of inflammatory mediators; 4) inhibited NF-small ka, CyrillicB and mitogen-activated protein kinases (MAPKs) signal pathways; 5) reduced muscle necrosis and enhanced regeneration. Our results highlight the detrimental effects of oxidative stress and NF-kappaB, MAPKs and COX/5-LOX pathways in the dystrophic process and show that flavocoxid is more effective in mdx mice than methylprednisolone.
Comment
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Staff Comment by Pat Furlong on October 8, 2009 at 9:34am -
Traci, I am h opeful Raju (CINRG) and/or others will repeat the study. To be honest, with the information we have from this paper, I would not reduce the steroid dose. It is frustrating, I agree. while the paper has some interesting and potentially encouraging information, it needs further testing. I like answers. yes or no. But it is difficult as you know because of the spectrum of the disorder. There is considerable variation in the boys (age, specific mutation, progression and genetic modifiers), and for this reason, clinical trials are essential in order for definitive information. The other side of this, is that some compounds (approved drugs, medical foods, supplements) are not expected to provide significant benefit and will not go to trial. This is one reason we see 'waves' going through the community - creatinine, protandim, etc. No easy answers..
It would be interesting to think about cohort trials or patient driven trial with DuchenneConnect. In this way, the community could 'test' nutraceuticals, compounds, etc. Together we could develop a protocol, ask specific questions and have the patients/families report on a consistent basis. It would be essential to report everything, no just progress and stick with it. For instance, reporting on the effect (good/bad), side effects and if a decision was made to stop and why (interpreted that it had no effect, expense, compliance). While this would not be viewed as a clinical trial, it would provide relevant information. The thing is that these 'waves' go through the community with parents suggesting something works and families jump onboard. Often we hear really glowing reports of benefit in the short term, but nothing over time. So, we never learn if whatever benefit was seen continues, if there is change (positive or negative) and/or if the compound (supplement, medical food, nutraceutical) was discontinued and for what reason (no benefit, compliance, expense, etc). Seems to me, we could set up a system that would help us collect the data and over time, be able to understand trends of benefit or not.
I know there are a few docs willing to help us set up the system on DuchenneConnect.
Just an idea... .
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Comment by Traci Strafuss on October 7, 2009 at 3:25pm -
Could this Flavocoxid be useful enough as an "add-on" to steroid therapy? Might it allow a lower dose or alternative dosing schedule that might then reduce steroid side effects? Will researchers take another look at this product, that is available and apparently safe, or will it be pushed aside and dismissed?
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Staff Comment by Pat Furlong on October 6, 2009 at 5:28pm -
Agree, interesting, needs to be repeated in a major lab. Agree as well, that certain approved drugs, supplements, medical foods may be additive. But it is critical to verify results before setting your heart /hope on bold claims of benefit.
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