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Parkinson's Disease Clinical Study: 2 of 5 using NADH - Life's Energy Source
(pg 2 of 5)
ACTUAL CLINICAL STUDY:
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A New Therapeutic Approach for Treating PARKINSON'S DISEASE
Indirect evidence for the central role of TH in the biosynthesis of dopamine has been gained long ago by applying (alpha) - methylparatyrosine, an inhibitor of TH, to parkinsonian patients. Under this medication the disability of the patients deteriorated indicating a further reduced L-DOPA biosynthesis ( 5 ). In 1981 Nagatsu and coworkers ( 6 ) showed that H4 biopterin, the coenzyme of TH, is reduced to about 50% in the brain of parkinsonian patients in comparison to that of age matched healthy control. This may be one of the reasons for the reduced TH activity.
For the time being the first choice of therapy is till substitution by L-DOPA which is the end product of TH and readily converted into dopamine. L-DOPA is known to act as feedback inhibitor of TH ( 7 ). Thus the exogenous supplied L-DOPA will inhibit TH activity already reduced in parkinsonian patients even further. Taking this account we considered a new concept to overcome the dopamine deficit namely to stimulate TH activity in order to increase L-DOPA biosynthesis. This may be accomplished by adding the reduced or missing cofactors. Since we know that the coenzyme of TH H4biopterin is also reduced in the brain of parkinsonian patients, therapeutic application of this substance was considered. However, clinical trial with H4biopterin did not show any beneficial clinical effect with Parkinsonian patients ( 8, 9 ). The failure of this approach was the impermeability of the blood brain barrier for H4biopterin. Therefore, this substance cannot reach its target, the substantia nigra in the brain. The question was whether it is possible to stimulate the H4 biopterin biosynthesis in the brain. The H4 biopterin deficiency could be due either to a decreased biosynthesis or to a lack in the biological active form. If a diminished biosynthesis of H4 biopterin is the cause of TH defect, stimulation of H4 biopterin biosynthesis should elevate the enzyme activity. The key enzyme in H4 biopterin biosynthesis is the quinoidH2pteridin reductase ( 10 ). This enzyme needs the reduced nicotinamide adenine dinucleotide (NADH) as coenzyme. Our idea was to stimulate H4 biopterin biosynthesis by applying NADH which increases the quinonoid H2 pteridine reductase activity and due to this amount of H4 biopterin increases. Owing to this NADH may stimulate endogenous L-DOPA biosynthesis by the postulate mechanism. An increase in L-DOPA production should be reflected by an improvement of the clinical symptoms of parkinsonian patients. In order to investigate our concept in more detail more than 800 parkinsonian patients have been treated with NADH and the possible mechanism of action of NADH has been studied in a dopamine producing neuroblastoma cell-line.
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