voner
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this one certainly needs some comments by someone who is following research closely and understands some of the biochemistry (unlike me):
http://www.faqs.org/patents/app/20100286073
the Patent cites numerous examples and a small study -- here's a quote describing how the patent author, Paul JENKINS , "discovered" this potential treatment:
The inventors arrived at the present discovery (forming the basis of the invention) in a completely unexpected fashion. While treating a subject suffering from a cardiac condition with an anti-anginal agent, trimetazidine, the inventors discovered that, within a short time after commencement of treatment, that same subject, also suffering from fibromyalgia syndrome, experienced a surprising and remarkable improvement in all symptoms associated with his fibromyalgia. This effect was later further confirmed in additional clinical studies of fibromyalgia patients for whom currently existing treatments for fibromyalgia had previously been either minimally or completely ineffective.
[0011]Trimetazidine (1-(2,3,4-trimethyloxybenzyl)piperazine) is a metabolic anti-anginal and anti-ischaemic agent that is used in the treatment of patients with coronary heart disease and stable angina. Unlike the conventional anti-anginal agents, which act by producing haemodynamic changes to restore balance between myocardial oxygen supply and demand, trimetazidine increases cellular tolerance to ischaemia.
[0012]Trimetazidine is thought to act by inhibiting mitochondrial fatty acid metabolism and secondarily by stimulating glucose metabolism (Kantor, et al., Circ Res, 2000, 86: 580-8). In particular, it has been shown that trimetazidine inhibits the long-chain isoform of an enzyme involved in mitochondrial fatty acid beta-oxidation, 3-ketoacyl coenzyme A thiolase (3KCT), thereby reducing fatty acid oxidation. An associated increase in pyruvate dehydrogenase activity stimulates glucose oxidation. This is thought to be due to the relief of fatty acid-induced inhibition of pyruvate dehydrogenase.
[0013]Thus, based on the surprising discovery that trimetazidine can be used to treat fibromyalgia and related conditions, the inventors have deduced that any substance that acts in the same manner, i.e. that inhibits fatty acid oxidation and/or stimulates carbohydrate metabolism, should also be effective in treating fibromyalgia and related conditions.
-- but considering that the DR. Kathy Light of University Utah has published results on benefits of a beta blocker, Propranolol, being beneficial for CFS/FM patients, and Trimetazidine is listed as a "alternative to beta blockers"..... curious..?
http://eurheartjsupp.oxfordjournals.org/content/3/suppl_O/O12.abstract
the Patent cites numerous examples and a small study -- here's one example:
Example 3
Treatment of Human Subject Diagnosed with Fibromyalgia with Trimetazidine
[0242]A 32 year old female presented with a 5 year history of complaints of widespread pain--headaches, upper and lower back pain, neck pain, hip pain bilaterally and knee pain bilaterally. General non-specific symptoms were fatigue, symptoms of irritable bowel syndrome (constipation-type), insomnia, morning stiffness and emotional liability.
[0243]Physical Examination: A physical examination revealed tender points located at: [0244](i) the sub-occipital muscle insertions bilaterally, at the occiput [0245](ii) the medial fat pads of the knees, just proximal to the joint lines, bilaterally [0246](iii) the trapezius muscles, at the midpoint of the upper border of the muscles, bilaterally [0247](iv) the greater trochanter, posterior to the trochanteric prominence, bilaterally [0248](v) the supraspinatus muscles, at the origins, above the spine of the scapula near the medial border, bilaterally.
[0249]Laboratory Tests: The following laboratory investigations were conducted: CBC, ESR, CRP, Rheumatoid Factor, Thyroid Function Tests, ANA. These tests yielded no positive results. X-Rays were also taken and resulted in no positive findings.
[0250]Patient History of Prior Treatment: A patient history was taken. Prior treatments targeting pain relief were as follows. OTC analgesics such as paracetamol (also known as acetaminophen), NSAIDs and low dose codeine provided negligible pain relief. Prescription analgesics such as high dose codeine, tramadol and meperidine provided, at best, mild to moderate and very temporary relief and were frequently accompanied by unpleasant side effects. Trigger point injections were refused by the patient.
[0251]Prior treatments targeting other symptoms included the following. The subject had taken tegaserod for irritable bowel syndrome. Additional prior therapies included zolpidem, midazolam, zopiclone, and chlorpheniramine for insomnia.
[0252]All of the above therapies were either minimally effective or completely ineffective.
[0253]Diagnosis: The subject was diagnosed with fibromyalgia syndrome.
[0254]Treatment Regime: The subject was administered trimetazidine (modified release formulation, Vastarel MR), 35 mg orally, twice daily.
[0255]Results: Within 24 hours of starting treatment, there was vast improvement in all symptoms and signs of fibromyalgia. Positive results were as follows. The subject reported a "95% reduction" in the widespread pain, with a residual mild headache. The subject additionally reported very significantly increased energy levels, very significantly improved sleep patterns (described as "uninterrupted and very restful"), markedly improved regularity of bowel habits, and very improved mood.
[0256]Follow-up. After four (4) months of continuous use of trimetazidine (modified release) 35 mg, orally, twice daily, the patient has reported that she continues to experience the same marked improvement in the quality of her life. She has experienced no relapse of symptoms to date.
A quick search I could find only one other reference (1998) to Trimetazidine in FMS, and none in CFS...
http://www.jacn.org/cgi/content/full/17/3/300
here is a quote:
These complex thiamin abnormalities might explain reduced nitric oxid (and impaired muscle relaxation and microcirculation) or glutathione (and muscle soreness) [6], impaired glycolysis (and muscle fatigue) [5] or even serotonin depletion (and decreased pain threshold) [10] observed in FM.
Whatsoever, even if excessive alcohol intake is not a FM risk factor, conversely to hypothyroidism or detraining, appropriate metabolic treatment is needed, particularly when blood pyruvate is elevated [5]. Cocarboxylase (IM or sublingual) is markedly more efficient than thiamin alone [11] or magnesium [16] and further studies on other B vitamins (pyridoxal phosphate, riboflavine, folates, thioctic acid), minerals (Mg, manganese, selenium), amino acids (arginine, S-adenosyl methionine, cysteine) or drugs stimulating pyruvate dehydrogenase activity (trimetazidine, carnitine) and phosphorylations (phosphocreatinine, piracetam) are needed [6,10,15].
//////////////////////////////
Who is "Paul Jenkins"? The patent lists him as living in England.
I find this one intriguing. They claim an elimination of fatigue, pain, etc............I guess I suspect another subgroup!
........comments? Speculation?
http://www.faqs.org/patents/app/20100286073
the Patent cites numerous examples and a small study -- here's a quote describing how the patent author, Paul JENKINS , "discovered" this potential treatment:
The inventors arrived at the present discovery (forming the basis of the invention) in a completely unexpected fashion. While treating a subject suffering from a cardiac condition with an anti-anginal agent, trimetazidine, the inventors discovered that, within a short time after commencement of treatment, that same subject, also suffering from fibromyalgia syndrome, experienced a surprising and remarkable improvement in all symptoms associated with his fibromyalgia. This effect was later further confirmed in additional clinical studies of fibromyalgia patients for whom currently existing treatments for fibromyalgia had previously been either minimally or completely ineffective.
[0011]Trimetazidine (1-(2,3,4-trimethyloxybenzyl)piperazine) is a metabolic anti-anginal and anti-ischaemic agent that is used in the treatment of patients with coronary heart disease and stable angina. Unlike the conventional anti-anginal agents, which act by producing haemodynamic changes to restore balance between myocardial oxygen supply and demand, trimetazidine increases cellular tolerance to ischaemia.
[0012]Trimetazidine is thought to act by inhibiting mitochondrial fatty acid metabolism and secondarily by stimulating glucose metabolism (Kantor, et al., Circ Res, 2000, 86: 580-8). In particular, it has been shown that trimetazidine inhibits the long-chain isoform of an enzyme involved in mitochondrial fatty acid beta-oxidation, 3-ketoacyl coenzyme A thiolase (3KCT), thereby reducing fatty acid oxidation. An associated increase in pyruvate dehydrogenase activity stimulates glucose oxidation. This is thought to be due to the relief of fatty acid-induced inhibition of pyruvate dehydrogenase.
[0013]Thus, based on the surprising discovery that trimetazidine can be used to treat fibromyalgia and related conditions, the inventors have deduced that any substance that acts in the same manner, i.e. that inhibits fatty acid oxidation and/or stimulates carbohydrate metabolism, should also be effective in treating fibromyalgia and related conditions.
-- but considering that the DR. Kathy Light of University Utah has published results on benefits of a beta blocker, Propranolol, being beneficial for CFS/FM patients, and Trimetazidine is listed as a "alternative to beta blockers"..... curious..?
http://eurheartjsupp.oxfordjournals.org/content/3/suppl_O/O12.abstract
the Patent cites numerous examples and a small study -- here's one example:
Example 3
Treatment of Human Subject Diagnosed with Fibromyalgia with Trimetazidine
[0242]A 32 year old female presented with a 5 year history of complaints of widespread pain--headaches, upper and lower back pain, neck pain, hip pain bilaterally and knee pain bilaterally. General non-specific symptoms were fatigue, symptoms of irritable bowel syndrome (constipation-type), insomnia, morning stiffness and emotional liability.
[0243]Physical Examination: A physical examination revealed tender points located at: [0244](i) the sub-occipital muscle insertions bilaterally, at the occiput [0245](ii) the medial fat pads of the knees, just proximal to the joint lines, bilaterally [0246](iii) the trapezius muscles, at the midpoint of the upper border of the muscles, bilaterally [0247](iv) the greater trochanter, posterior to the trochanteric prominence, bilaterally [0248](v) the supraspinatus muscles, at the origins, above the spine of the scapula near the medial border, bilaterally.
[0249]Laboratory Tests: The following laboratory investigations were conducted: CBC, ESR, CRP, Rheumatoid Factor, Thyroid Function Tests, ANA. These tests yielded no positive results. X-Rays were also taken and resulted in no positive findings.
[0250]Patient History of Prior Treatment: A patient history was taken. Prior treatments targeting pain relief were as follows. OTC analgesics such as paracetamol (also known as acetaminophen), NSAIDs and low dose codeine provided negligible pain relief. Prescription analgesics such as high dose codeine, tramadol and meperidine provided, at best, mild to moderate and very temporary relief and were frequently accompanied by unpleasant side effects. Trigger point injections were refused by the patient.
[0251]Prior treatments targeting other symptoms included the following. The subject had taken tegaserod for irritable bowel syndrome. Additional prior therapies included zolpidem, midazolam, zopiclone, and chlorpheniramine for insomnia.
[0252]All of the above therapies were either minimally effective or completely ineffective.
[0253]Diagnosis: The subject was diagnosed with fibromyalgia syndrome.
[0254]Treatment Regime: The subject was administered trimetazidine (modified release formulation, Vastarel MR), 35 mg orally, twice daily.
[0255]Results: Within 24 hours of starting treatment, there was vast improvement in all symptoms and signs of fibromyalgia. Positive results were as follows. The subject reported a "95% reduction" in the widespread pain, with a residual mild headache. The subject additionally reported very significantly increased energy levels, very significantly improved sleep patterns (described as "uninterrupted and very restful"), markedly improved regularity of bowel habits, and very improved mood.
[0256]Follow-up. After four (4) months of continuous use of trimetazidine (modified release) 35 mg, orally, twice daily, the patient has reported that she continues to experience the same marked improvement in the quality of her life. She has experienced no relapse of symptoms to date.
A quick search I could find only one other reference (1998) to Trimetazidine in FMS, and none in CFS...
http://www.jacn.org/cgi/content/full/17/3/300
here is a quote:
These complex thiamin abnormalities might explain reduced nitric oxid (and impaired muscle relaxation and microcirculation) or glutathione (and muscle soreness) [6], impaired glycolysis (and muscle fatigue) [5] or even serotonin depletion (and decreased pain threshold) [10] observed in FM.
Whatsoever, even if excessive alcohol intake is not a FM risk factor, conversely to hypothyroidism or detraining, appropriate metabolic treatment is needed, particularly when blood pyruvate is elevated [5]. Cocarboxylase (IM or sublingual) is markedly more efficient than thiamin alone [11] or magnesium [16] and further studies on other B vitamins (pyridoxal phosphate, riboflavine, folates, thioctic acid), minerals (Mg, manganese, selenium), amino acids (arginine, S-adenosyl methionine, cysteine) or drugs stimulating pyruvate dehydrogenase activity (trimetazidine, carnitine) and phosphorylations (phosphocreatinine, piracetam) are needed [6,10,15].
//////////////////////////////
Who is "Paul Jenkins"? The patent lists him as living in England.
I find this one intriguing. They claim an elimination of fatigue, pain, etc............I guess I suspect another subgroup!
........comments? Speculation?
